Document 23547

TABLE OF CONTENTS
Use the page numbers and your mouse to navigate the file!
Date of revision: 5 May 2014
INTRODUCTION ........................................................................................................ IV Hospital medicines list (HML) and antimicrobial guidelines ..................................... v Infectious Disease Service: Consultation Policy ..................................................... vi Prescribing and endorsement of medicines deemed “Specialist” medications within
the Pharmac Community Schedule ........................................................................ vii Acknowledgements................................................................................................. vii Principles of empiric antimicrobial prescribing ....................................................... viii Antimicrobial cost awareness ................................................................................. ix BLOOD CULTURES – WHEN, WHY, HOW ............................................................... 1 Procedures to follow after notification of a positive blood culture ............................ 2 Management Of Patients With Positive Blood Cultures........................................... 4 Management of Confirmed Staphylococcus aureus Bacteraemia ........................... 6 TREATMENT GUIDELINES FOR COMMON CONDITIONS IN ADULT PATIENTS .... 7 IDENTIFICATION AND MANAGEMENT OF SEVERE SEPSIS ................................. 8 NEUTROPENIC FEVER IN ADULT PATIENTS ....................................................... 13 NEUTROPENIC FEVER IN PAEDIATRIC PATIENTS ............................................. 15 CARDIOVASCULAR SYSTEM INFECTIONS .......................................................... 17 Infective Endocarditis (IE) ...................................................................................... 17 CENTRAL NERVOUS SYSTEM INFECTIONS ........................................................ 20 Community-Acquired Meningitis in Adults1 ............................................................ 20 Herpes Simplex Encephalitis ................................................................................. 22 EAR, NOSE AND THROAT INFECTIONS ................................................................ 24 Acute Otitis Media.................................................................................................. 24 Acute Sinusitis ....................................................................................................... 25 Chronic Sinusitis .................................................................................................... 26 Pharyngitis ............................................................................................................. 27 RESPIRATORY TRACT INFECTIONS ..................................................................... 28 Exacerbations of COPD And Chronic Bronchitis ................................................... 28 Pneumonia............................................................................................................. 29 Tuberculosis .......................................................................................................... 33 Influenza ................................................................................................................ 34 GASTROINTESTINAL TRACT AND INTRA-ABDOMINAL INFECTIONS ............... 35 Dental and Gingival Infections ............................................................................... 35 Acute Peritonitis ..................................................................................................... 36 Cholecystitis / Cholangitis ...................................................................................... 37 Acute Pancreatitis/Severe Necrotising Pancreatitis............................................... 38 Infectious Diarrhoea............................................................................................... 39 Clostridium difficile disease ................................................................................... 40 Typhoid / Paratyphoid Fever.................................................................................. 41 Helicobacter Pylori Infection .................................................................................. 42 URINARY TRACT INFECTIONS .............................................................................. 43 Cystitis ................................................................................................................... 43 Uncomplicated pyelonephritis ................................................................................ 44 Complicated UTI .................................................................................................... 45 Ciprofloxacin prescribing policy ............................................................................. 46 GENITAL TRACT INFECTION .................................................................................. 47 Pelvic Inflammatory Disease ................................................................................. 48 Bacterial Vaginosis ................................................................................................ 49 Candidosis / Vulvo-Vaginitis .................................................................................. 50 Chlamydial Cervicitis / Urethritis ............................................................................ 51 Genital Herpes Simplex ......................................................................................... 52 Gonorrhoea............................................................................................................ 53 Non-Gonococcal Urethritis..................................................................................... 54 Trichomoniasis....................................................................................................... 55 Syphilis .................................................................................................................. 55 SKIN, MUSCLE AND BONE INFECTIONS .............................................................. 56 Osteomyelitis - Acute ............................................................................................. 56 Septic Arthritis - Non Prosthetic Joint .................................................................... 57 Septic Arthritis - Prosthetic Joint ............................................................................ 57 Bites and Clenched Fist Injuries ............................................................................ 58 Compound Fractures ............................................................................................. 59 Cellulitis - Simple ................................................................................................... 60 Cellulitis - Complicating Ulcer ................................................................................ 61 Necrotising Fasciitis or Synergistic Gangrene ....................................................... 62 Mastitis / Breast Abscess....................................................................................... 63 Wound Infections ................................................................................................... 64 EYE INFECTIONS .................................................................................................... 65 Blepharitis .............................................................................................................. 65 Conjunctivitis.......................................................................................................... 66 TRAVELLERS’ INFECTIONS ................................................................................... 67 Malaria ................................................................................................................... 67 TREATMENT GUIDELINES FOR COMMON CONDITIONS IN PAEDIATRIC
PATIENTS .................................................................................................................... 69 Cellulitis ................................................................................................................. 69 Conjunctivitis Neonatorum ..................................................................................... 70 Epiglottitis .............................................................................................................. 70 Meningitis............................................................................................................... 71 Osteomyelitis - Acute ............................................................................................. 73 Otitis Media – Acute............................................................................................... 74 Periorbital / Orbital Cellulitis................................................................................... 75 Pharyngitis ............................................................................................................. 76 Pneumonia............................................................................................................. 77 Pyelonephritis ........................................................................................................ 78 Urinary Tract Infections.......................................................................................... 79 Aminoglycoside Dosing In Children ....................................................................... 80 GUIDELINES FOR EFFECTIVE USE OF ANTIMICROBIAL DRUGS ........................ 83 INFORMATION ON SELECTED ANTIMICROBIAL DRUGS .................................... 83 Antibacterial Drugs ................................................................................................ 84 Antiviral Drugs ....................................................................................................... 91 Antifungal Agents................................................................................................... 92 DOSING, PHARMACOKINETICS AND PHARMOCODYNAMICS ........................... 95 Gentamicin: Principles of Usage and dosing ......................................................... 97 Vancomycin Dosing ............................................................................................. 102 Metronidazole Dosing .......................................................................................... 103 Beta-Lactam Dosing ............................................................................................ 104 IMPAIRED RENAL FUNCTION .............................................................................. 105 HEPATIC INSUFFICIENCY .................................................................................... 109 OBESE PATIENTS ................................................................................................. 110 PREGNANCY AND LACTATION ............................................................................ 111 Drugs in Pregnancy ............................................................................................. 111 Drugs in Lactation ................................................................................................ 112 ORAL ANTIMICROBIAL THERAPY........................................................................ 115 Switch Therapy .................................................................................................... 115 Selecting an Appropriate Oral Antimicrobial Drug ............................................... 116 ii
PROPHYLACTIC USE OF ANTIMICROBIAL DRUGS ............................................. 118 SURGICAL PROPHYLAXIS.................................................................................... 118 ENDOCARDITIS PROPHYLAXIS ........................................................................... 123 Antibiotic Regimens ............................................................................................. 123 SPLENECTOMY ..................................................................................................... 125 Prevention of Severe Infections ........................................................................... 125 Treatment Of Post-Splenectomy Sepsis.............................................................. 125 APPENDICES ............................................................................................................. 126 OUTPATIENT INTRAVENOUS THERAPY ............................................................. 126 Long Term IV Antibiotics...................................................................................... 126 Short Term IV Therapy ........................................................................................ 126 Chronic/Speciality Patients Requiring IV Therapy ............................................... 126 Community Cellulitis Protocol .............................................................................. 127 LOCAL RESISTANCE PATTERNS TO ANTIMICROBIAL DRUGS ....................... 128 Infection incidence summary report 2013 ............................................................ 135 MRSA Management ............................................................................................ 141 BLOOD AND BODY FLUID EXPOSURES ............................................................. 146 NOTIFIABLE DISEASES IN NEW ZEALAND ......................................................... 148 How To Notify A Notifiable Disease ..................................................................... 149 iii
INTRODUCTION
This booklet is intended as a guide for the initial treatment of common conditions. It
takes into account agreed best practice in clinical infectious disease nationally and
internationally, uses local antimicrobial sensitivities to offer empiric (“best guess”)
antibiotic choices and complies with Pharmac regulations in relation to restricted
antimicrobials http://www.pharmac.health.nz/medicines/hospital-pharmaceuticals.
This document has been developed by Waikato District Health Board (Waikato DHB)
specifically for its own use. Use of this document and any reliance on the information
contained therein by any third party is at their own risk. Recommendations are based
on current (March 2014) international clinical practice and may sometimes differ from
product registration information. This handbook has been developed in association with
the Waikato Hospital clinical services and is approved for use within Waikato District
Health Board.
We trust that you will find these guidelines helpful.
Paul Huggan
Graham Mills
Infectious Diseases Physicians
Chris Mansell
Clinical Microbiologist
iv
Hospital medicines list (HML) and antimicrobial guidelines
1. The Hospital Medicines List (HML) – Section H of the Pharmaceutical Schedule
came into effect on 1July 2013. The HML lists the pharmaceuticals which are
funded for use in DHB hospitals in NZ. Prescribing within DHB hospitals must
conform to the regulations set out in the HML. See:
http://www.pharmac.health.nz/medicines/hospital-pharmaceuticals.
2. Many antimicrobials listed in the HML are now restricted to the approval of ID and
clinical microbiology staff (and a limited number of other specialists in some
circumstances).
3. Drugs listed on the HML and listed in this antimicrobial guideline are indicated with
a superscript H (e.g. meropenemH) and are automatically approved for use for
the condition and duration stated.
4. For drugs, listed on the HML but not in this antimicrobial guideline (or for
indications, duration or doses not covered in this guideline), treating
clinicians will have to seek approval from a clinical infectious disease
specialist or clinical microbiologist before the drug can be dispensed
from pharmacy. The haematology and intensive care units are specifically
exempted as a formal multi-disciplinary team approach, involving infectious
diseases and clinical microbiology exists.
5. For drugs not listed on the HML (or indications not listed on the HML),
treating clinicians will have to seek approval from a clinical infectious
disease specialist or clinical microbiologist AND approval from
PHARMAC (following their Rapid Assessment or NPPA process) before
the
drug
will
be
ordered
by
pharmacy.
See:
http://www.pharmac.health.nz/tools-resources/forms/named-patientpharmaceutical-assessment-nppa-forms#nppaapplication
6. The New Zealand Health and Disability Services (Infection Prevention and
Control) Standards – Infection Control Management (NZS 8134.3:2008)
includes a requirement to promote the prudent prescribing of antibiotics. For
Waikato DHB to comply with this standard, ongoing auditing of the use of
antibiotics is required. This handbook will form the antibiotic standard that our
practice will be audited against.
7. Guidelines can only provide guidance and are not a substitute for thoughtful
clinical decision making and common sense. The guideline authors acknowledge
that the antibiotic choices suggested here will be appropriate in 90% of the
patients, 90% of the time. For that reason, any HML antimicrobial can be
prescribed with the approval of a senior medical officer for the first 24 hours of a
patient’s hospital admission. Beyond 24 hours, restricted pharmaceuticals will
only be dispensed with the approval of a named infectious disease or clinical
microbiologist (see Infectious Disease Service: Consultation Policy).
v
Infectious Disease Service: Consultation Policy
1. The infectious disease and microbiology departments have limited resources and at
the time of writing cannot provide routine in-person consultation for all patients.
Telephone consultation will often be the only option and is always available.
2. Telephone advice is potentially unsafe and therefore only appropriate if the details of
a case are transmitted accurately and the outcome of the conversation documented
and properly interpreted by the referrer (http://www.medicalprotection.org/uk/sessionalgp-issue-6)
3. Antimicrobial prescribing requires a broad understanding of the patient’s clinical
background, early progress, likely management and prognosis. The referrer retains
medico-legal responsibility for prescribing and must interpret telephone advice in the
light of their superior knowledge of the patient (i.e. renal function, drug allergies).
4. Therefore, where information and advice is sought by telephone, the ID
consultant should only be contacted by a senior member of the referring clinical
team, i.e. registrar or consultant.
5. The outcome of the conversation must be documented in the clinical record by the
referrer. Email may be used to reach an appropriate recommendation for complex
cases.
6. Subsequent updates and advice can be sought by other members of the team
provided the ID consultant who provided the initial opinion is available to discuss the
case.
vi
Prescribing and endorsement of medicines deemed
“Specialist” medications within the Pharmac Community
Schedule
To be funded in community some medicines require endorsement on the prescription –
to state that the medicine is written by or recommended by a specialist.
PHARMAC has revised endorsement requirements when prescribing medications
classified as “Retail pharmacy–Specialist”, which came into effect on the 1st July 2013.
Any “Retail pharmacy-Specialist” medications (as defined in the schedule) will only be
eligible for subsidy if the prescription is either signed by a relevant specialist or
recommended by a relevant specialist. If recommended then the prescription needs to
be endorsed with either:
i) The words “recommended by [name of Specialist and year of authorisation]” and
signed; or
ii) Endorsed with the word ‘protocol’ which means “initiated in accordance with DHB
hospital approved protocol”
Current antimicrobials affected by these policies include:
•
Cefoxitin, Cefuroxime, ClindamycinH, Colistin, TB medications including
rifampicin, fluconazole, fusidic acid and ketoconazole.
A help desk has been set up for any PHARMAC queries relating to the Hospital
Medicine List:
email [email protected]
phone 0800 66 00 50 or
fax 64 4 974 7819.
Source: Pharmacy Services Memorandum, 19 June 2013
Acknowledgements
The following documents have been helpful in the production of this handbook and are
gratefully acknowledged:
Antibiotic Guidelines, Victorian Medical Postgraduate Foundation Inc,
14th Edition, 2010.
Canterbury District Health Board Antimicrobial Guidelines 16th Edition 2012
Guide to Pathogens and Antibiotic Treatment 7th Edition, Selwyn Lang, 2004.
New Zealand Pharmaceutical Schedule, Pharmac, December 2013.
Principles and Practice of Infectious Diseases, Mandell, Douglas, Bennett,
7th Edition, 2010.
vii
Principles of empiric antimicrobial prescribing
Always remember that an alternative to the recommendations in this guideline is always
available and is only a phone-call or a good textbook away. In most cases, antimicrobial
treatment is initiated before a causative organism is known.
A major role of
microbiological laboratory testing is to enable the spectrum of the antibiotic used to be
narrowed with confidence. Remember that restraint in the use of all antimicrobials is
the best way to ensure their continuing efficacy.
The principles of prescribing remain straightforward, but the ever-increasing number of
alternatives has made the task complex. The following concepts underpin prescribing:
Efficacy:
Therapy has to be effective for the suspected condition in the
majority of circumstances. Although efficacy is an over-riding
concern, the problem that we encounter is not so much a lack of
choice, but too many regimens that are equally effective.
Tolerability:
The choice has to have an acceptable side effect profile and
ease of administration. Some of the most difficult antibiotic
selection problems arise, not from resistant organisms, but when
a patient has contraindications to several classes of drugs. It is
important to document the nature of any adverse reaction so
that a patient is not inadvertently re-exposed, nor unnecessarily
disadvantaged in future by a label of “drug allergy”.
Economically Sound:
Given the wide choice and the constraints on health spending,
cost has to be considered if two products are similar. With the
movement to generic antibiotics, many antibiotics have become
considerably cheaper in recent years. Remember that an
effective oral regimen is always superior to an intravenous
regimen.
Ecological Impact:
Awareness is needed of the impact of antibiotic selection
pressure on the hospital environment and beyond. Ignoring this
will lead to ever increasing resistance problems.
The choices that have been made in this handbook reflect these concepts. The aim of
this guideline is to provide effective first-line therapy for all patients.
viii
Antimicrobial cost awareness
Cost awareness is an important factor that needs to be considered in choosing
antibiotics. Agents of similar efficacy can vary in cost by greater than a 1000% - yet
often because of pharmaceutical company marketing efforts, the more expensive agent
is chosen. Remember that a non-marketed antibiotic does not mean an ineffective
antibiotic. Often it is simply that the patent has run out! The dosage regimen used for
cost comparison is an indication only and should not be used as a dosing guideline for
all infections. The stated costs in this table are based on hospital acquisition costs as
at August 2012 and should be seen as approximate only. Prices are subject to change
over time.
Drug
Route
Av. Adult Dose*
Hospital Cost
Cost/Unit Cost/Day
($)
($)
ANTIBACTERIALS
Cephalosporins
Cephalexin
500mg
Cefaclor
250mg
Cephazolin
500mg
Cefotaxime
1g
Cefoxitin
1g
Cefuroxime axetil 500mg
Cefuroxime
750mg
Ceftriaxone
1g
CeftazidimeH
1g
H
Cefepime
1g
PO
PO
IV/IM
IV/IM
IV/IM
PO
IV/IM
IV/IM
IV/IM
IV/IM
250mg q6h
250mg q8h
1g q6h
1g q8h
1g q6h
500mg q12h
750mg q8h
1g q24h
1g q8h
1g q12h
0.45
0.25
1.60
1.56
11.00
0.59
1.39
2.10
6.49
8.80
0.89
0.74
6.40
4.67
44.00
1.18
4.18
2.10
19.47
17.60
500mg
1g
500mg
PO
IV/IM
PO
500mg q8h
1g q8h
500mg q8h
0.05
2.19
0.13
0.15
6.57
0.39
1.2g
IV
1.2g q8h
1.65
4.95
500mg
600mg
500mg
1g
4.5g
PO
IV/IM
PO
IV
IV/IM
500mg q6h
600mg q6h
500mg q6h
1g q6h
4.5g q8h
0.23
1.15
0.15
1.43
12.00
0.93
4.60
0.60
5.71
36.00
3.1g
IV/IM
3.1g q6h
18.00
72.00
1g
1g
IV/IM
IV/IM
1g q8h
1g q24h
21.00
70.00
63.00
70.00
Penicillins
Amoxycillin
Amoxycillin
Amoxycillin/
clavulanate
Amoxycillin/
clavulanate
Penicillin V
Benzylpenicillin
Flucloxacillin
Flucloxacillin
Piperacillin/
tazobactamH
Ticarcillin/
clavulanateH
Carbapenems
MeropenemH
ErtapenemH
* Calculations based on body weight of 70kg
ix
Drug
Route
Av. Adult Dose*
ANTIBACTERIALS
Aminoglycosides
Gentamicin
80mg
TobramycinH
80mg
H
Amikacin
500mg
IV/IM
IV/IM
IV/IM
400mg q24h
400mg q24h
1g q24h
0.65
5.86
77.00
3.25
29.32
154.00
Glycopeptides
VancomycinH
500mg
TeicoplaninH
400mg
IV
IV/IM
1g q12h
400mg q24h
3.58
113.39
14.32
113.39
400mg
PO
400mg q6h
0.17
0.68
1g
IV
1g q6h
10.93
43.72
300mg
250mg
500mg
PO
PO
PO
300mg q24h
500mg q12h
1g stat
0.29
0.30
2.98
0.29
1.20
5.95
Fluoroquinolones
Norfloxacin
400mg
H
Ciprofloxacin
500mg
CiprofloxacinH
200mg
H
Moxifloxacin
400mg
PO
PO
IV
PO
400mg q12h
500mg q12h
200mg q12h
400mg q24h
0.15
0.11
4.10
10.40
0.31
0.21
8.20
10.40
Nitroimidazoles
Metronidazole
500mg
Metronidazole
500mg
Metronidazole
400mg
IV
PR
PO
500mg q12h
500mg q12h
400mg q12h
2.46
2.45
0.18
4.92
4.90
0.36
Tetracyclines
Doxycycline
100mg
PO
100mg q24h
0.03
0.03
150mg
600mg
480mg
480mg
PO
IV/IM
PO
IV
300mg q6h
600mg q8h
960mg q12h
960mg q12h
0.62
16.00
0.04
22.00
4.95
48.00
0.16
88.00
50mg
300mg
PO
PO
50mg q8h
300mg q24h
0.22
0.18
0.66
0.18
Macrolides
Erythromycin
ethylsuccinate
Erythromycin
lactobionate
Roxithromycin
ClarithromycinH
AzithromycinH
Miscellaneous
ClindamycinH
ClindamycinH
Cotrimoxazole
Cotrimoxazole
Fusidic Acid
Nitrofurantoin
Trimethoprim
* Calculations based on body weight of 70kg
x
Hospital Cost
Cost/Unit Cost/Day
($)
($)
Drug
Route
Av. Adult Dose*
ANTIBACTERIALS
Antituberculins
Isoniazid
100mg
Pyrazinamide
500mg
Rifampicin
600mg
PO
PO
PO
300mg q24h
2000mg q24h
600mg q24h
50mg
50mg
IV
IV
50mg
200mg
100mg
100mg
200mg
250mg
200mg
200mg
ANTIVIRALS
Acyclovir
Hospital Cost
Cost/Unit Cost/Day
($)
($)
0.20
0.59
3.81
0.60
2.36
3.81
50mg q24h
200mg q24h
27.41
345.00
27.41
1380.00
IV
PO
IV
PO
PO
PO
PO
IV
50mg q24h
200mg q24h
200mg q24h
100mg q24h
200mg q24h
250mg q24h
200mg q12h
200mg q12h
667.50
0.48
5.68
0.28
1.27
0.13
59.80
217.46
667.50
0.48
11.36
0.28
1.27
0.13
119.60
434.92
200mg
PO
0.08
0.40
Acyclovir
400mg
PO
0.12
0.59
Acyclovir
800mg
PO
0.21
1.05
Acyclovir
250mg
IV
ValganciclovirH
450mg
PO
Ganciclovir
500mg
IV
Foscarnet
6000mg
IV
200mg 5 times
daily
400mg 5 times
daily
800mg 5 times
daily
Indication
dependent
Indication
dependent
Indication
dependent
Indication
dependent
ANTIFUNGALS
AmphotericinH
Amphotericin
liposomalH
CaspofunginH
Fluconazole
Fluconazole
ItraconazoleH
Ketoconazole
Terbinafine
VoriconazoleH
VoriconazoleH
* Calculations based on body weight of 70kg
xi
5.10
50.00
76.00
140.00
BLOOD CULTURES – WHEN, WHY, HOW
Bloodstream infection represents a serious and potentially life threatening stage of an
infective process where the infection is no longer contained within an organ space or
system. Depending on the organism involved bloodstream infections carry a high
morbidity and mortality risk.
A blood culture is a diagnostic test. The performance of the test changes dramatically
based on factors that alter sensitivity and specificity:
How to increase true positives
(  sensitivity)
Take blood cultures before administering
antibiotics in all but the sickest patients
• especially important in
endocarditis and patients in whom
fever may not relate to infection
(i.e. PE, drug fever, burns,
pancreatitis)
Fill each blood culture bottle properly
• standard culture bottle: 10ml
• paediatric culture bottle: 3ml
• myco-flytic cultures:
5ml
How to increase false positives
(↓ specificity)
Culture through peripheral lines, central
lines and PICC lines without taking
peripheral cultures at the same time
• vascular access cultures are
frequently contaminated by
colonising organisms
Take all bottles from a single draw
• this preserves sensitivity but
doesn’t help to diagnose
contamination if cultures are
positive
Fail to adhere to aseptic technique
Take more cultures
• take a minimum of 4 but ideally 6
bottles for culture (3 aerobic + 3
anaerobic) from 2 separate draws
Take cultures from each lumen of a
vascular access device if a suspected
source of infection
Take blood cultures from patients with no
indication to have the test
Good blood culture technique, adequate sampling and interpretation of positive results
are the responsibility of all clinicians and nurses involved in patient care.
Failing to secure a microbiologic diagnosis exposes the patient to harm both through
use of inappropriate antibiotics and/or failure to link an organism to an underlying
diagnosis (ie Streptococcus bovis as an indicator of underlying bowel cancer).
Optimal diagnosis of bacteremia/fungemia is achieved with 3 aerobic/anaerobic sets of
blood cultures (see below).
Sequential sensitivity (%) of blood cultures for monomicrobial
bacteremia/fungemia J Clin Micro 2007; 45: 3546-48
Microorganism
Staphylococcus aureus
Coagulase negative staphylococci
Enterococcus spp
Streptococci
Escherichia coli
Klebsiella pneumoniae
Pseudomonas aeruginosa
Candida albicans
Candida glabrata
Cumulative number of blood cultures drawn
1
2
3
87
93
100
71
98
100
68
87
100
85
100
65
90
100
76
88
100
62
94
100
60
83
100
80
100
1
Procedures to follow after notification of a positive blood
culture
Interpretation of Laboratory Reports
Positive blood cultures are phoned through when the organism has grown in the blood
culture bottle and has been gram-stained. The following table gives some guidance to
interpreting the gram-stain description of the organism. Initially this is all the
information that will be available, as the organism then needs to grow on agar plates
overnight before it can be identified further.
Antimicrobial susceptibility and
identification to species level take a further 12-48 hrs. A rapid coagulase test will often
give an indication that a gram-positive coccus is Staphylococcus aureus 2- 4 hrs after
the initial gram stain result is available.
All positive blood culture results should be followed up urgently. If a doctor receives a
report for a patient that is not directly under his/her care, it is the responsibility of the
doctor to check that suitable treatment is under way.
2
Interpretation of Blood Culture Gram Stain Reports
Description of
Gram Stain
Most Serious
Possible
Cause of Infection
Most Likely Cause
of Infection
Other Possible Causes
of Infection
- Clusters
Staph. aureus
Coagulase-negative
Staph (usually
contaminant)
Micrococcus
Aerococcus
Anaerobic gram- positive
Coccus
- Pairs
(diplococci)
- Chains
Strep. pneumoniae
Strep. pneumoniae
Group A Strep
Group B Strep
Viridans strep group
GRAM-POSITIVE
BACILLI
Listeria
monocytogenes
Bacillus anthracis
Diphtheroids
(Corynebacteria or
Propionibacterium
acnes - both are
usually
contaminants).
GRAM-NEGATIVE
COCCI
Neisseria
meningitidis
Neisseria
meningitidis
- Pairs
(diplococci)
Neisseria
meningitidis
E. coli-like
organisms
(Coliform)
e.g. Klebsiella,
Enterobacter,
Proteus,
Serratia,
Yersinia
Neisseria
meningitidis
Coliform
e.g. E. coli
Klebsiella,
Enterobacter,
Proteus,
Serratia,
Yersinia
Campylobacter
fetus
Candida albicans
Campylobacter
jejuni
Candida albicans
GRAM-POSITIVE
COCCI
GRAM-NEGATIVE
BACILLI
- Curved
YEAST
3
Group C or G Strep
Strep milleri or Strep
anginosus
Anaerobic gram-positive
coccus
Erysipelothrix
Bacillus sp (Aerobic
spore-forming grampositive bacillus)
Clostridium (Anaerobic
spore-forming grampositive bacillus)
Commensal Neisseria
Strep pneumoniae
Anaerobic gram-negative
cocci
Gram-negative
coccobacilli
e.g. Kingella,
Acinetobacter sp
Neisseria gonorrhoeae
Pseudomonas-like
organisms
Stenotrophomonas
maltophilia
Anaerobic gramnegative bacilli
e.g. Bacteroides sp
Aeromonas
Haemophilus
Other Candida sp
e.g. C. krusei,
C. glabrata
Management Of Patients With Positive Blood Cultures
1.
Possible Staphylococcus aureus bacteraemia
(Gram positive cocci in clusters in a patient with sepsis)
•
•
•
•
•
•
•
Visit within 2 hr unless diagnosis has been made and antibiotic already given.
Repeat blood cultures (all lumens of IV lines plus peripheral).
Sample obvious sites of infection.
Check notes for MRSA alert and susceptibility of previous isolates.
Antibiotic of choice is IV flucloxacillin 1-2g every 6 hours.
Discuss with any other medical teams involved and notify patient’s own team
next day.
Staph aureus infection can lead to significant complications from inadequate
therapy. For this reason, Waikato Hospital has specific guidelines on how to
manage this condition (see below).
2. Possible Meningococcal bacteraemia
(Any Gram-Negative Cocci)
•
•
Urgently phone ward to check whether IV ceftriaxone 1g every 12 hours or any
other antibiotic is being given.
If diagnosis has not already been made, then visit patient urgently (<1hr).
3. Possible Gram-Negative Sepsis
(Any Gram-Negative Bacilli)
•
•
•
•
•
•
•
•
•
•
Urgently phone ward to check whether any IV antibiotic is being given.
If patient is stable and has already been treated, visit within 4 hr to document in
notes.
Briefly check the patient.
Check that specimens have been sent: urine for culture + dipstick, swab any
wounds, sputum if available, diarrhoea if present, ideally more than one set of
blood cultures before antibiotics, gentamicin levels.
Notify patients’ own team first thing next working day.
If diagnosis has not already been made or if antibiotics have not yet been
given, visit urgently (<1hr).
Assess urinary tract, genital tract, abdomen, respiratory tract, recent surgical
sites, recent antibiotic history and gentamicin level results if available.
If UTI give gentamicin 5mg/kg IV once daily.
If abdominal infection, give gentamicin 5mg/kg IV daily + amoxycillin 1g IV
every 6 hours + metronidazole 500 mg IV every 12 hours.
If PID, take cervical bacterial and chlamydial swabs and urine for chlamydia,
give Augmentin and doxycycline and refer to O&G.
4
4. Possible Pneumococcus Infection
(Gram-Positive Diplococci)
•
•
•
•
•
•
Urgently phone ward to check whether any antibiotic is being given.
If diagnosis has not already been made or if antibiotics have not yet been
given, visit urgently (<1hr).
Check that the following tests have been done and whether any results are
available:
ABG, FBC, CXR, sputum, ± repeat blood cultures, check ears and sinuses,
possibility of meningitis.
If patient is stable and has already been started on treatment, visit within 4
hours to record details of test results in notes. Briefly check patient.
Appropriate antibiotics include any penicillin or cephalosporin. Ciprofloxacin or
macrolides such as erythromycin alone are not adequate.
Consult General Medical or Respiratory team if patient is under the care of
another team.
5. Suspected Endocarditis or Subacute PUO Associated With Any
Murmur or Embolic Symptom
(Streptococci or Staph. aureus, for patient with any abnormal valve).
•
•
Visit patient within 4 hours.
Check the following tests have been done:
• 3 sets of blood cultures, preferably from different sites.
• Perform a clinical review for changing murmur, decompensated heart
failure, sepsis syndrome and emboli, particularly cerebral.
• Discuss with General Medicine or Cardiology before giving further
antibiotics or arranging TTE or TOE.
6. Apparent Contaminant
(Coagulase Negative Staph or Gram-Positive Bacilli from patient who is well)
•
•
•
•
Check patient history and confirm organism involved.
Carefully repeat blood cultures if necessary (see blood culture guidelines).
Do not attribute coagulase negative staphylococci, viridans streptococci or
unidentified gram positive bacilli to contamination if the patient is ill or has a
prosthetic heart valve or implanted endovascular device (ie pacemaker).
Update consultant responsible for patient.
5
Management of Confirmed Staphylococcus aureus Bacteraemia
BACKGROUND
Staphylococcus aureus bacteraemia (SAB) is a common problem in Health Waikato
patients with about a hundred positive cultures every year. An audit of local practice
recently identified several problems in the management of SAB with common underinvestigation and inadequate IV antibiotic treatment.
Approach to Management
ID consultation is not mandatory at Waikato DHB but is encouraged, particularly if there
is any doubt as to the source of bacteraemia, the adequacy of initial response to
treatment or the final duration of therapy (see below).
1) Notification of blood cultures positive for Staphylococcus aureus.
The requesting doctor will be notified as soon as the blood culture becomes positive
and the patient’s consultant is to be notified after confirmation of SAB with a standard
letter.
2) Use of echocardiography
All patients with signs of endocarditis or community-onset SAB (blood cultures positive
within 48 hours of hospital admission) should undergo trans-thoracic
echocardiography. Trans-oesophageal echocardiography should be considered on a
case by case basis but is usually required for patients with prosthetic heart valves or
permanent pacemakers. Discuss with an infectious disease specialist if in doubt.
3) Further investigation
•
•
•
Cultures should be repeated at 48-72 hours
Direct investigations according to the clinical presentation and dominant findings
Deep sources of SAB that are commonly missed include: spinal
osteomyelitis/discitis, septic arthritis, renal and psoas abscesses, infection of
implanted devices (i.e. pacemaker wires) and thrombophlebitis.
4) Antibiotic treatment and duration
In general, patients should receive 2 weeks of intra-venous antibiotics before cessation
of treatment is considered. Stopping treatment after 2 weeks is reasonable providing
all of the following are satisfied;
•
•
•
Complete, focused clinical investigation has effectively ruled out deep-seated
infection that would mandate longer periods of treatment by standard guidelines
(i.e. endocarditis, prosthetic device or graft infection, spinal
osteomyelitis/discitis)
There has been a complete clinical response with negative blood cultures at
48-72 hours.
No ongoing symptoms, clinical or laboratory findings exist that raise suspicion
of deep infection (i.e. new back pain)
The duration of intravenous therapy for patients with bacteraemia in the setting of a
deep focus of infection depends on the nature of the underlying infection and is usually
longer than two weeks.
All cases of clinical concern should be discussed with an infectious disease
specialist.
6
TREATMENT GUIDELINES FOR COMMON
CONDITIONS IN ADULT PATIENTS
7
IDENTIFICATION AND MANAGEMENT OF
SEVERE SEPSIS
Sepsis is the systemic response to infection. Septic patients present in all areas of the
hospital and diagnosis is frequently delayed. Delays in diagnosing and treating sepsis
can contribute to the progression of severe sepsis, defined as sepsis in the presence
of organ failure or tissue hypoperfusion. The following guide outlines how to identify
each of these disorders and the ACTION to take if sepsis/severe sepsis are confirmed.
Identifying and managing the septic patient
Sepsis = confirmed/suspected infection AND 2 or more SIRS criteria: Temp >38C or
<36C, HR>90, RR>20 or PaCO2<32mmHg, WBC>12,000 or <4000 or “left shift”
ACTION:
•
•
•
•
•
•
•
Secure IV access and run fluid
Give supplemental oxygen to maintain SpO2 above 93%
Send new bloods for FBC, renal panel, LFT, venous blood gas (arterial in
hypoxic patients) and lactate, draw 3 sets of blood cultures
Request diagnostic tests to confirm diagnosis
Prescribe antibiotic according to guideline and ensure patient receives first dose
within one hour of review
Recheck clinical observations/ADDS within 2 hours
Ensure that nursing staff and the registrar in charge of the patient are informed
of change in patient’s condition and any treatment plans. Discuss these with the
consultant in charge as necessary
Review investigations – is this severe sepsis? IN HOSPITAL MORTALITY 10-50%
Severe sepsis = sepsis AND new organ dysfunction AND/OR hypoperfusion AND/OR
hypotension
*Hypotension = SBP <90mmHg, MAP <70 or >40mmHg decrease in SBP from patient
baseline
Organ dysfunction = change in mental status (new confusion or delirium); increase in
oxygen requirements; new rise in creatinine above 175 micromol/L; urine output
<0.5ml/kg/hr for 2 hours despite adequate fluids; platelets <100; INR >1.5 or aPTT>60
sec; total bilirubin > 34 micromol/L; serum lactate >2 mmol/L
ACTION:
•
•
•
•
•
As for sepsis but stay with the patient to ensure that all steps completed; focus
on resuscitation end points of normalised lactate after 4 hours, adequate urine
output, improvement in conscious level, oxygenation and blood pressure
Give 500ml NSaline over 15 minutes and repeat up to 2 litres as necessary
Move quickly to identify, debride and drain all accessible sources of infection as
soon as possible, including out of normal office hours
Ensure your consultant is involved and get ICU/HDU input early if the patient is
eligible for intensive organ support.
Note: hypotension is often a late sign in sepsis – the normotensive patient with
organ dysfunction is at high risk of in-hospital mortality
8
“Best Guess” Antibiotic Choice in Severe Sepsis
Empiric antibiotic therapy should ideally be based on localising symptoms and signs of
infection. If none are present, the diagnostic tests required for localisation should be
performed as soon as possible.
All empiric antibiotic regimens are intended for 24 to 72 hours only and should be
modified as soon as possible based on clinical progress, pathogen identification and
susceptibility testing.
1) Sepsis - community onset: unknown site
Pathogens:
Gram-negative organisms, Staphyloccus aureus, Neisseria meningitidis, Streptococcus
pneumoniae
DRUG
DOSE (for normal renal function)
Empiric
Cefriaxone
2g IV q12 hourly
and
Gentamicin
See gentamicin dosing guidelines
Treatment Duration:
This is an empiric initial therapy only
and should only continue for the first 48
hours and should be altered at that
time based on microbiology results
9
2) Sepsis + Urinary Tract INFECTION (Pyelonephritis, renal/perinephric
abscess)
For immunocompetent patients presenting with lower urinary tract infection without
systemic toxicity, refer to the section on urinary tract infection.
Cystitis associated with the sepsis syndrome +/- flank or loin pain is by definition
a complicated urinary tract infection – initial treatment should be with an IV
agent.
Pathogens:
Enterobacteriaceae, Pseudomonas aeruginosa.
DRUG
DOSE
Empiric
Amoxicillin
1g IV q8 hrly
and
Gentamicin
Refer to gentamicin dosing guidelines
10
3) Sepsis + Skin and soft tissue infection
Pathogens:
Staphylococcus aureus, Group A Streptococci.
DRUG
DOSE
Empiric – cellulitis/myositis
Flucloxacillin 1,2
2g iv 6 hourly
Empiric – deep ulceration or
suspicion of necrotising fasciitis2
Benzylpenicillin
2.4g iv q4h
and
CeftazidimeH
2g iv q8h
and
ClindamycinH
600mg IV q8h
1
There is no need to combine flucloxacillin and benzylpenicillin in soft tissue infection;
flucloxacillin has excellent activity against Group A Streptococci.
2
Use only for clinically severe infections – apply LRINEC Score and consider surgical
review if ≥6 - revise diagnosis after 24-48 hours, consult readily for cases of
gangrene, necrotising fasciitis and infected ulceration in diabetics and patients with
vascular compromise of affected limb.
4) Sepsis and hepatobiliary disease/obstruction
Pathogens:
Enterobacteriaceae, Anaerobes, Enterococcus
DRUG
DOSE
Ceftriaxone
2g IV q24 hourly
and
Metronidazole
500mg iv inf 12 hourly
11
5) Sepsis with peritonitis
Pathogens:
Enterobacteriaceae, anaerobes, enterococci
DRUG
DOSE
Cefuroxime1,2
750mg IV q8 hourly
and
Metronidazole
500mg IV q8 hourly
and if pelvic inflammatory disease
suspected
Doxycycline
100mg PO q12 hourly
1
Adjust in renal impairment: eGFR 10-20ml/min give 750mg bd. eGFR <10ml/min give
750mg daily.
2
Most patients with treated/resolving peritonitis can complete therapy with oral coamoxyclavulanate unless microbiologic evidence of resistant infection.
6) Sepsis + line infection (including central lines)
Pathogens:
Coagulase-negative staphylococci, Staphylococcus aureus, Gram-negative rods,
Candida sp.
DRUG
DOSE
Flucloxacillin
2g iv 6 hourly1
and
Gentamicin
1
Refer to gentamicin dosing guidelines
Line-associated MRSA infection is currently very unusual at WDHB facilities. Empiric
vancomycin is not recommended.
7) Sepsis + suspected meningitis
See section on central nervous system infections (below)
12
NEUTROPENIC FEVER IN ADULT PATIENTS
Definition
Neutropenic fever is a body temperature ≥38.3oC or ≥38.0oC on two occasions over at
least one hour in a patient who is severely neutropenic (i.e. neutrophil count
< 0.5 x 109 /L).
Principles Of Therapy
•
•
•
•
•
•
•
All patients who become febrile whilst severely neutropenic must be assessed by
medical staff within 20 minutes of the fever (as defined above) developing.
Treatment is empiric.
Antibiotic therapy is commenced without an isolated organism or even possible site
of infection.
Antibiotic choice must be broad spectrum, particularly covering gram-negative
organisms, which carry a high morbidity and mortality.
Currently, all antibiotics are given intravenously with a high degree of urgency. The
first dose of intravenous antibiotics should be given within 30 minutes.
Patients on Ward M5 at Waikato Hospital will be routinely reviewed by their
consultant each day.
For patients in other locations (especially at T Hospitals), the relevant
haematologist or oncologist should be contacted within 24 hours of admission or
commencing treatment for neutropenic fever to discuss ongoing management.
After hours, or at weekends, this should be discussed with the on-call consultant.
First Line Therapy
Summary
Providing there is no known allergy, severe renal impairment (estimated creatinine
clearance less than 30ml/min) or previous use of cisplatin, the recommended
combination treatment is tobramycinH and piperacillin/tazobactamH (Tazocin).
Alternative regimens, as described below, must be used for patients in whom the usual
first line therapy is likely to cause severe toxicity. If there is any uncertainty, the
haematologist or oncologist on- call should be contacted for discussion.
1. Usual First Line Therapy (Tazocin® and TobramycinH)
TazocinR (Piperacillin + Tazobactam)
The conventional starting dose in adults is 4.5g 8 hourly IV. Adjustments of
dosage are made for severe renal impairment i.e. if creatinine clearance less than
30ml/min, use 4.5g 12 hourly.
13
TobramycinH
In adults this should be commenced with a single dose of 5 mg/kg IV, regardless of
gender or age. TobramycinH can be discontinued if blood cultures are negative for
Pseudomonas aeruginosa or other multi-drug resistant pathogens. Doses should
be calculated using ideal body weight (IBW), or actual weight, if this is less than
IBW. If actual weight is >20% above IBW, dosing should be based on the Obese
Dosing Weight (ODW). The dosing interval should be in accordance with
estimated creatinine clearance, based on an extended interval regimen (see
section on aminoglycoside dosing). Beware of continuing aminoglycosides for
prolonged periods of time given the complication of renal toxicity and
ototoxicity which are more likely to occur with treatment durations of more
than seven days.
2. Patients with Penicillin Allergy but without Anaphylaxis
(CefepimeH and TobramycinH)
CefepimeH is a fourth generation cephalosporin with slightly broader spectrum
activity than ceftazidimeH. The usual dose is 2 g 12 hourly IV. Cross allergy with
penicillins is estimated to be less than five percent. Usually, the benefits of highly
potent gram-positive cover will outweigh the possible risk of allergic reactions.
Tobramycin should be commenced with a single dose of 5 mg/kg IV, regardless of
gender or age. TobramycinH can be discontinued if blood cultures are negative for
Pseudomonas aeruginosa or other multi-drug resistant pathogens. Doses should
be calculated using ideal body weight (IBW), or actual weight, if this is less than
IBW. If actual weight is >20% above IBW, dosing should be based on the Obese
Dosing Weight (ODW). The dosing interval should be in accordance with
estimated creatinine clearance as per the Cockcroft formula, based on an
extended interval regimen (see guidelines on Aminoglycoside dosing). Beware of
continuing aminoglycosides for prolonged periods of time given the
complication of renal toxicity and ototoxicity which are more likely to occur
with treatment durations of more than seven days.
3. Patients Receiving Nephrotoxic Drugs or Previously Treated with
Cisplatin
Monotherapy with IV cefepimeH 2g 12 hourly is recommended.
4. Patients with Severe Renal Impairment (Calculated creatinine
clearance <30ml/min)
Monotherapy with IV cefepimeH 1g 12 hourly is recommended for treatment of
patients with severe renal failure. Aminoglycosides and intravenous vancomycin
are not usually recommended for treatment of patients with severe renal failure.
However, they may be used in life-threatening situations after consultation with the
specialist on call.
Subsequent Changes in Antimicrobial Therapy
Changes from first line therapy will be made by the Haematology or Oncology team,
with the guidance of a departmental protocol. Antibacterial spectrum may be widened,
antifungal or antiviral therapy may be added or treatment may be narrowed or
discontinued in light of laboratory results or changes in the patient’s clinical condition.
If a change in antimicrobial therapy appears indicated out of hours, please discuss with
the haematologist or oncologist on call.
14
NEUTROPENIC FEVER IN PAEDIATRIC
PATIENTS
Protocol adapted from Auckland Starship Hospital Protocol for Treatment of Febrile
Neutropenia in Children for use at Waikato Hospital (May 2005).
Definitions
•
Fever: Temperature > 38.0°C on two consecutive occasions within 2 hours, or
>38.5°C on one occasion.
•
Neutropenia: A neutrophil count of <0.5 x 109/L
Evaluation Of Patient
• Examine patient.
• Obtain CBC.
• Culture blood from all lumens for bacteria and fungi and indicate which culture bottle
contains blood from which lumen.
• Peripheral culture should be taken if possible.
• Culture other sites as clinically indicated.
• Order CXR/urine specimens, as clinically indicated.
Risk Groups
RISK FACTORS
Absolute neutrophil count
LOW RISK
0.1 – 0.5 x 109/L
HIGH RISK
<0.1 x 109/L
Duration of neutropenia
<7 days
>7-10 days
Comorbidity
Nil
Toxic/clinical focus/
High-dose Ara-C
Treatment
i)
•
•
•
Low Risk
First line therapy is cefepimeH 50 mg/kg/dose 8-12 hourly (max 4g/day)
Evaluate after 48 hours.
- If afebrile with negative cultures and still neutropenic, discharge home on once
daily IV ceftriaxone 80 mg/kg/day (max 2g/day). This can be given by District
Nurse until neutrophil and platelet counts start to increase or until absolute
neutrophil count >0.5 x 109/L.
- If still febrile with negative cultures, reassess and re-culture. Add tobramycinH
5mg/kg/dose 24 hourly.
Note: TobramycinH/Ceftriaxone is inadequate for Pseudomonas.
If still febrile at 96 hours, consider consulting ID team (Auckland Starship Hospital)
for reassessment and individualised therapy.
15
ii) High Risk
•
•
•
•
First line therapy is tobramycinH 5mg/kg/dose 24 hourly and Timentin
(ticarcillin/clavulanate) 75mg/kg/dose (ticarcillin) 6 hourly (max 12g/day).
Evaluate after 48 hours.
- If afebrile with negative culture and still neutropenic, consider discharge home
to return to ward or outreach for once daily iv ceftriaxone 80mg/kg/day (max
2g/day) and tobramycinH (5 mg/kg/dose).
- District nurse not to give.
- Such patients will need a daily medical review, temperature and CBC.
- Antibiotics should continue until absolute neutrophil count >0.5 x 109/L.
- If still febrile with negative cultures, reassess and reculture.
- Add IV vancomycin 20-30 mg/kg/dose 8 or 12 hourly (max 2g/day).
If still febrile at 96 hours, consult ID team (Auckland Starship Hospital) for
reassessment.
- Consider meropenemH (20-40 mg/kg/dose) 8 hourly (max 3g/day).
If still febrile at 5-7 days, consider amphotericinH 0.5mg/kg/day, increasing to
1.5mg/kg/day, or fluconazole, if there is renal impairment.
Monitoring Levels
•
•
Vancomycin
TobramycinH (8 hourly dosing)
•
TobramycinH (daily dosing)
Troughs only prior to the 4th dose.
Peak after 3rd dose and trough prior to
the 4th dose.
Trough prior to 2nd dose – refer to
Aminoglycoside nomogram
16
CARDIOVASCULAR SYSTEM INFECTIONS
Infective Endocarditis (IE)
The diagnosis and management of IE rests on coupling positive blood cultures with
evidence of endocardial involvement in an infective process. This forms the basis of the
major Duke criteria for diagnosis of IE, which are a useful clinical guide.
In suspected IE, take a minimum of 3 sets of blood cultures (6 bottles, 3 aerobic and 3
anaerobic) drawn from 2 venepuncture sites more than one hour apart.
Take all blood cultures before any antibiotics are given. If antibiotics have been given
within two weeks take 6 sets of blood cultures.
Duke criteria for diagnosis of endocarditis [Clin Infect Dis 2000; 30: 633-8]
Definitive diagnosis
• Histologic or microbiologic studies of valve tissue confirming endocarditis
OR
• 2 major clinical criteria; or
• 1 major clinical criterion and 3 minor criteria; or
• 5 minor clinical criteria
Possible diagnosis
• 1 major criterion and 1 minor criterion; or
• 3 minor criteria.
Rejected diagnosis
• Firm alternate diagnosis explaining evidence of infective endocarditis syndrome
or
• Resolution of infective endocarditis syndrome with antibiotic therapy for ≤4
days; or
• No pathologic evidence of infective endocarditis at surgery or autopsy, with
antibiotic therapy for ≤4 days; or
• Does not meet criteria for possible infective endocarditis, as above.
Major Clinical Criteria
1. Major Microbiologic Criteria
• Typical micro-organisms consistent with IE from 2 separate blood cultures:
Viridans streptococci, Streptococcus bovis, HACEK organisms, Staphylococcus
aureus or community-acquired enterococci in the absence of a primary focus; or
• Micro-organisms consistent with IE from persistently positive blood cultures,
defined as follows:
- At least 2 positive cultures of blood samples drawn >12 h apart; or
- All of 3 sets of blood cultures or
- A majority of ≥4 separate cultures of blood with first and last sample drawn at
least 1 hour apart.
• or single positive blood culture for Coxiella burnetti or antiphase I IgG antibody
titre>1:800
17
2. Evidence of endocardial involvement
A. Echocardiogram positive for IE
• TOE is recommended in patients with:
- prosthetic valves, rated at least “possible IE” by clinical criteria, or
- complicated IE (perivalvular abscess or poor clinical response to treatment);
• TTE is the first test in other patients, with positive results defined as:
- oscillating intracardiac mass on valve or supporting structures, in the path of
regurgitant jets, or on implanted material in the absence of an alternative
anatomic explanation; or
- Abscess; or
- New partial dehiscence of prosthetic valve.
B. New valvular regurgitation
(worsening or changing of pre-existing murmur not sufficient)
Minor Criteria
1. Predisposition
• Predisposing heart condition or intravenous drug use.
2. Fever
• Temperature >38oC
3. Vascular phenomena
•
•
•
•
•
•
Major arterial emboli
Septic pulmonary infarcts
Mycotic aneurysm
Intracranial haemorrhage
Conjunctival haemorrhages
Janeway's lesions.
4. Immunologic phenomena
•
•
•
•
Glomerulonephritis
Osler’s nodes
Roth’s spots
Positive rheumatoid factor
5. Microbiological evidence
• Positive blood culture that does not meet a major criterion as noted above, or
• Serological evidence of active infection with organism consistent with IE except
as indicated above.
18
Empiric Treatment for Suspected Endocarditis:
DRUG
Empiric1
(a) Native Valve
Benzylpenicillin
and
Gentamicin
and
Flucloxacillin
(b) Prosthetic Valve
VancomycinH
and
Gentamicin
DOSE
1.8g iv 4 hourly
3 mg /kg iv q24 hourly2
2g iv 4 hourly
30mg/kg/day (Up to 1.5g iv inf 12 hourly)
3 mg /kg iv q 24 hourly2
1
Consult Cardiology Specialist and Infectious Disease specialists upon confirmation of
endocarditis or to direct investigation and treatment.
2
Low-dose gentamicin (3mg/kg q24 hourly) is used in synergy with other agents to
treat endocarditis and is continued for 14 days in most cases. Check a trough level
before giving the second dose and every 48 hours during the first week of treatment.
Counsel patients regarding symptoms of vestibular dysfunction and discuss with ward
pharmacist if either i) trough level >1 mg/L or ii) renal function deteriorates.
Specific Therapy for Endocarditis
•
•
Refer to relevant summaries available on UptoDate
Discuss with an infectious disease specialist once microbiology results available
19
CENTRAL NERVOUS SYSTEM INFECTIONS
Community-Acquired Meningitis in Adults1
Empiric 1
DRUG/DOSE in
Normal Renal
Function
Day 1
1. In all cases
Ceftriaxone2 2g IV q12 hourly
2.Are Gram positive cocci resembling
streptococcus seen in CSF (see
below)?
If yes, add to ceftriaxone:
Dexamethasone 10mg IV (0.15mg/kg in
children) with antibiotics3
plus
Vancomycin 30mg/kg/day in divided
doses (up to 1.5g q12 hourly)
3. Is L.monocytogenes a possibility
(see risk factors below)?
If yes, add to ceftriaxone:
Amoxicillin 2g IV q 4hrly
or in penicillin allergic patients
Trimethoprim/Sulfamethoxazole
5mg/kg based on trimethoprim
component IV q 8 hourly
Day 2 onwards
Streptococcus pneumoniae:
+ve Gram stain of CSF: positive blood culture; pneumococcal
antigen test on CSF3
Ceftriaxone
2g IV q12h
and
VancomycinH (until penicillin
susceptibility known)
and
Dexamethasone if commenced3
30mg/kg/day in divided doses (up to 1.5g q12
hourly)
Neisseria meningitidis
Ceftriaxone
2g IV q24h
For clearance of nasopharyngeal Neisseria meningitidis in close contacts4
Rifampicin
600mg PO 12 hourly for 2 days
or
Ceftriaxone
250mg IM as single dose
Listeria monocytogenes
Amoxycillin and
2g IV q4 hourly
Gentamicin
See gentamicin dosing guideline
20
•
•
•
•
CT prior to LP if:
- Impaired level of consciousness or lateralising neurological signs
- Features of raised intracranial pressure
- New onset seizures
- Shocked
- Sinus or ear infections.
If LP cannot be performed immediately, start antibiotics.
For patients with severe penicillin allergy or known mild-moderate penicillin allergy
who require cover for L.monocytogenes, see “First Dose Empiric Antibiotic
Guidelines in Adults” and/or consult an infectious disease specialist.
Carefully consider possible aetiologies in all cases
• Streptococcus pneumoniae: children; base of skull fracture, sinus or middle
ear infection; seizure; rapid onset with reduced consciousness at presentation
• Listeria monocytogenes: pregnancy, immunosuppression (CLL or Lymphoma,
high dose steroids, transplant), cirrhosis and those older than 60
• Neiserria meningitides: should be covered in all cases until microbiology
results available
• Haemophilus influenzae: should be covered in all cases until microbiology
results available. Important cause of meningitis in children and young adult but
becoming less common due to vaccination
1
Discussion with an infectious disease or microbiology specialist is recommended.
Third generation cephalosporins are inactive in meningitis caused by L.
monocytogenes.
3
Due to the possibility of resistance, Health Waikato policy determines that evidence of
pneumococcal meningitis (gram positive cocci resembling streptococci seen in CSF)
requires treatment with both ceftriaxone and vancomycin until sensitivity results
become available ceftriaxone alone if sensitive. Treatment with dexamethasone 10mg
IV (0.15mg/kg in children) at the time of the first dose of antibiotic is recommended for
meningitis due to Streptococcus pneumoniae as it is considered to improve outcomes
in both adults and children. If initial investigations confirm S.pneumoniae meningitis
dexamethasone is continued at the dose above q6hrly for 4 days. There is no
evidence that delayed starting of dexamethasone i.e. more than four hours after
starting antibiotics, is helpful (N Engl J Med. 2004;351(18):1849).
4
Prophylaxis is not recommended routinely for medical personal except those who
have had intimate exposure such as occurs with unprotected mouth to mouth
resuscitation, intubation or suctioning before antibiotic therapy was begun.
Community contacts of N.meningitidis meningitis are determined by the Medical
Officer of Health.
2
Treatment Duration:
Meningococcal disease
3 days.
Streptococcus pneumoniae
7-10 days.
Staphylococcus or Listeria
Minimum of 14 days.
21
Herpes Simplex Encephalitis
• Consider if altered consciousness, seizures, or focal neurology.
• Fever and personality changes are uniformly present in Herpes simplex
encephalitis.
• LP usually abnormal with the presence of mononuclear cells.
• EEG may be characteristic.
• PCR testing is very sensitive and specific but should not be ordered prior to
knowledge of LP findings.
Pathogen:
Herpes simplex.
Drug Treatment:
DRUG
DOSE
Empiric
Aciclovir
10 mg/kg iv 8 hourly
Treatment Duration:
14 –21 days
Notes:
•
Most patients with biopsy-proven HSV encephalitis present with a focal
encephalopathic process characterised by altered mentation and decreasing levels
of consciousness with focal neurologic findings, including dysphasia, weakness
and paraesthesia. Fever and personality changes are uniformly present.
•
Approximately two-thirds of patients with biopsy-proven disease develop either
focal or generalised seizures.
•
Herpes simplex PCR on CSF is a very sensitive and specific diagnostic test. It will
usually only be performed with the presence of mononuclear cells in CSF.
•
It is therefore important to make all efforts to confirm the diagnosis.
•
All suspected cases of Herpes simplex encephalitis should be reviewed by the
Infectious Diseases Physician or Virologist so that PCR testing can be performed
in a timely manner
22
Brain Abscess
In the immunocompetent, most brain abscesses are polymicrobial with microaerophilic
cocci, including Streptococcus anginosus/milleri, and anaerobic bacteria
predominating. However, where the likely site of origin is the ear, enteric Gramnegative bacilli are commonly involved, while after trauma or surgery, Staphylococcus
aureus predominates.
In the immunocompromised, Nocardia species, Toxoplasma gondii and fungi such as
Cryptococcus species, Aspergillus species or Scedosporium species are more lily to
occur.
Modify therapy on the basis of Gram stain and culture results. Durations of IV
treatment from 2 to 6 weeks are used and depend on surgical drainage, clinical
response and radiological evidence of resolution.
Drug Treatment:
DRUG
DOSE
Empiric 1
Metronidazole
500mg IV 8-hourly
plus
Ceftriaxone
2g iv 12 hourly
For postneurosugical
brain abscess
VancomycinH
1.5g IV 12hourly
plus
CeftazidimeH
2g IV 8-hourly
23
EAR, NOSE AND THROAT INFECTIONS
Acute Otitis Media
•
•
•
•
True acute otitis media may be either viral or bacterial, but in either case is usually
a self-limiting disease (60% of placebo-treated children become pain-free in 24
hours and 80% of cases resolve without antibiotics).
Provision of adequate analgesia is necessary.
Treatment with antibiotics should be considered only after a 24 hour trial of
analgesia.
The NNT is 16; i.e. 16 children need to be treated at first presentation to prevent
one child experiencing pain at 2 to 7 days.
Pathogens:
Common:
Viral, Streptococcus pneumoniae, Haemophilus influenzae.
Other:
Streptococcus pyogenes, Moraxella catarrhalis, Staphylococcus aureus.
Drug Treatment:
DRUG
DOSE
Empiric
Amoxycillin
500mg po 8 hourly
Patients with penicillin allergy
Cotrimoxazole1
960mg po 12 hourly
Beta-lactamase producing organisms
(known or suspected)
Amoxycillin/clavulanate
1
500/125mg po 8 hourly
Avoid cotrimoxazole in pregnancy. Beware with use of cotrimoxazole in the elderly.
Treatment Duration:
5 days.
24
Acute Sinusitis
•
•
Sinus congestion often occurs with viral infection or allergy, which require no
antibacterial treatment.
Antibiotic therapy should be considered when at least 3 of the following features
are present:
- persistent (greater than a week) mucopurulent nasal discharge
- facial pain
- poor response to decongestants
- tenderness over the sinuses, especially unilateral maxillary tenderness
- tenderness on percussion of maxillary molar and premolar teeth.
- Fever 38.4º or more
Pathogens:
Common:
Viral, Streptococcus pneumoniae, Haemophilus influenzae.
Other:
Moraxella catarrhalis, Staphylococcus aureus, Gram-negative bacilli, anaerobes.
Drug Treatment:
DRUG
DOSE
Empiric
Amoxycillin
500mg po 8 hourly
Patients with penicillin allergy
Doxycycline2, or
Cotrimoxazole
3
100mg po 12 hourly
960mg po 12 hourly
Pathogens Known
Beta-lactamase producing organisms or anaerobes
Amoxycillin/clavulanate
500/125mg po 8 hourly
Staphylococcus aureus
Flucloxacillin4
500/125mg po 8 hourly
2
Avoid doxycycline in both pregnancy and children.
Avoid cotrimoxazole in pregnancy and the elderly.
4
For treatment of patients with penicillin allergy - see Empiric treatment.
3
Treatment Duration:
At least 10 days.
25
Chronic Sinusitis
Pathogens: NB: Microbiological diagnosis requires a biopsy or sterile aspirate
Common:
Anaerobes, Streptococci, Staphylococcus aureus.
Other:
Gram-negative bacilli, Pseudomonas aeruginosa.
Drug Treatment:
DRUG
DOSE
Empiric
Amoxycillin/clavulanate
500/125mg po 8 hourly
Patients with penicillin allergy
Doxycycline1, or
Cotrimoxazole
2
100mg po 12 hourly
960mg po 12 hourly
Pathogens Known
Pseudomonas aeruginosa (proven)
Ciprofloxacin1, H
500mg po 12 hourly
Staphylococcus aureus
Flucloxacillin3
500mg po 8 hourly
1
Avoid doxycycline and ciprofloxacin in both pregnancy and children.
Avoid cotrimoxazole in pregnancy.
3
For treatment of patients with penicillin allergy - see Empiric treatment.
2
Treatment Duration:
At least 14 days.
Note:
Consider referral to the ENT Service as structural abnormalities may be present.
26
Pharyngitis
•
•
•
Most cases of pharyngitis are caused by viral infection and therefore do not require
antibiotic therapy.
A bacterial cause of acute sore throat is more common in children aged 3 to 13
years (30-40%), than in children aged less then 3 years (5-10%) or adults (5-15%).
The four diagnostic features suggestive of Streptococcus pyogenes infection are:
- fever >38 C
- tender cervical lymphadenopathy
- tonsillar exudate
- no cough
Sore throats, though mostly viral, need to be taken seriously in New Zealand, where a
high rate of endemic rheumatic fever persists. As the sequelae of rheumatic fever are
so serious (including permanent cardiac impairment or death), the small chance of a
sore throat being caused by GAS, and potentially leading to rheumatic fever, cannot be
overlooked in clinical decision-making. Those at greatest risk are Maori or Pacific
peoples between the age of 3-45 living in lower socioeconomic areas of North Island.
See: http://www.nzma.org.nz/journal/122-1301/3746/algorithms.pdf
Pathogens:
Common:
Viral, Streptococcus pyogenes.
Other:
Corynebacterium diphtheriae, Chlamydia pneumoniae, Neisseria gonorrhoea,
Mycoplasma pneumoniae.
Drug Treatment:
DRUG
DOSE
Empiric
Phenoxymethylpenicillin
500mg po 12 hourly
Patients with penicillin allergy
Roxithromycin
300mg po daily
Pathogens Known
Streptococcus pyogenes
Phenoxymethylpenicillin
500mg po 12 hourly
Other organisms, or penicillin allergy
Roxithromycin
300mg po daily
Treatment Duration:
10 days
Note:
Diphtheria infections require urgent referral to a Specialist.
27
RESPIRATORY TRACT INFECTIONS
Exacerbations of COPD And Chronic Bronchitis
Pathogens:
Common:
Viruses, Streptococcus pneumoniae, Haemophilus influenzae.
Other:
Moraxella catarrhalis.
Antibiotics have only been shown to be effective when all 3 cardinal symptoms of acute
bacterial exacerbations are present: increased dyspnoea, increased sputum volume
and sputum purulence.
Drug Treatment:
DRUG
DOSE
Empiric1
Smokers
Amoxycillin/clavulanate
500/125mg po 8 hourly
Non Smokers
Amoxycillin
500mg po 8 hourly
Patients with penicillin allergy
Doxycycline2
100mg po 24 hourly
Pathogens Known
Streptococcus pneumoniae
Amoxycillin
500mg po 8 hourly
Penicillinase- producing Haemophilus influenzae or Moraxella catarrhalis
Amoxycillin/clavulanate
500/125mg po 8 hourly
1
2
Empiric treatment is often used in moderate to severe exacerbations.
Avoid doxycycline in pregnancy and children.
Treatment Duration:
Variable depending on clinical response.
Notes:
•
•
There is no indication for IV therapy in the treatment of chronic bronchitis.
If pneumonia is diagnosed, refer to pneumonia protocol.
28
Pneumonia
Pathogens:
Common:
Streptococcus pneumoniae.
Other:
Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila,
Staphylococcus aureus, Moraxella catarrhalis, Klebsiella pneumoniae, Chlamydia
pneumoniae.
The choice of antibiotic for CAP is usually empirical, because the clinical presentation
and CXR appearances are not sufficiently specific to direct therapy against any one of
the likely causative organisms, and stand microbiological tests have a relatively low
yield.
Community Acquired - Mild / Moderate Disease (CURB Score ≤2)
Drug Treatment:
DRUG
DOSE
Empiric
Amoxycillin
1g po 8 hourly
1 g iv 8 hourly1
Patients with COPD or smokers
Amoxycillin/Clavulanate
1g/200mg iv 8 hourly1
500/125mg po 8 hourly
Patients with penicillin allergy
Roxithromycin
1
300mg po daily
IV therapy is usually only necessary when concerns are held regarding
absorption of oral antibiotics. Treatment with “atypical agents” is not usually
recommended in mild/moderate pneumonia
Treatment Duration:
Usually 5 - 7 days depending on severity.
Aspiration pneumonia
10 days
Atypical pneumonia
14 days
29
Community Acquired - Severe Disease (CURB Score ≥3)
Definition:
Community acquired pneumonia with at least two of the following CURB-65 risk
factors:
- Confusion
- Urea >7mmol/l
- Respiratory rate > 30/min
- Diastolic BP < 60mmHg
- Age >65years
Drug Treatment:
DRUG
Erythromycin
and
Amoxycillin/clavulanate
DOSE
1g iv inf q6 hourly
1g/200mg iv q8 hourly
Treatment Duration:
7-10 days, although most patients will change to oral therapy within 24 hours.
Notes:
• Most patients admitted to hospital will not have severe disease by the above
definition.
• Most patients will be able to change to oral therapy within 24 hours.
If no pathogen is identified and the patient is improving, change iv amoxycillin/
clavulanate to oral amoxycillin 1g 8hrly and change IV erythromycin to oral
macrolide e.g. roxithromycin 300 mg daily.
• CXR changes will persist despite appropriate therapy for up to eight weeks
(dependent on age of patient and underlying lung condition).
• The new fluoroquinolone agents are not recommended for empiric management of
pneumonia at Waikato Hospital. They are not on the HML for the management of
pneumonia unless highly resistant pneumococci are proven.
• Erythromycin iv produces a high rate of phlebitis and may require central line
administration if prolonged administration is planned.
30
Hospital Acquired pneumonia
Nosocomial or hospital-acquired pneumonia is defined as pneumonia that is not
incubating at the time of admission to hospital and develops in a patient hospitalised for
longer than 48 hours. Most bacterial HAP occurs by microaspiration of bacteria
colonising the oropharynx or upper gastrointestinal tract of the patient. The spectrum
of potential pathogens associated with HAP may differ from that of community-acquired
pneumonia (CAP) as hospitalised patients more frequently develop colonisation of the
oropharynx with aerobic Gram-negative bacilli, and may also be at greater risk of
multiresistant hospital pathogens such as MRSA, ESBL etc.
Hospital Acquired – Mild or Moderate
Despite the change in spectrum of organisms, the use of amoxicillin/clavulanate
monotherapy remains appropriate
Hospital Acquired – Severe Infection only
Drug Treatment:
DRUG
DOSE
Gentamicin
See gentamicin dosing guideline
and
Amoxycillin/Clavulanate
1g/200mg iv 8 hourly
and
Erythromycin
1g iv inf 6 hourly1
1
The need for erythromycin is confined to empirical treatment of legionella. If this has
been excluded erythromycin can be discontinued.
Treatment Duration: 10 days
31
Aspiration Pneumonia
Drug Treatment:
DRUG
DOSE
Amoxycillin/Clavulanate
1g/200mg iv 8 hourly
or
ClindamycinH
600mg iv inf 8 hourly
Treatment Duration:
10 days.
Community / Hospital Acquired Infection-Pathogens Known
Drug Treatment:
DRUG
DOSE
Streptococcus pneumoniae
Amoxycillin
1g po 8 hourly
1 g iv 8 hourly
Staphylococcus aureus
Flucloxacillin
or
Vancomycin 1, H
1g iv 6 hourly
1g iv inf 12 hourly2
Klebsiella pneumoniae
Cefuroxime
750mg iv 8 hourly
Legionella pneumophila,
Mycoplasma pneumoniae
Erythromycin
500mg – 1g iv inf 6 hourly
1
2.
If methicillin-resistant, or patient has severe penicillin allergy
Adjust vancomycin dosing for renal function.
Treatment Duration:
Variable dependent on patient characteristics.
Notes:
•
•
•
Streptococcus pneumoniae still remains the most common cause of pneumonia
and must be adequately covered by any regime chosen.
If Legionella pneumophila is suspected, use high dose macrolide therapy. Please
seek Infectious Diseases advice. Legionella PCR can be undertaken on serum,
sputum or BAL at Waikato Hospital.
Although pneumococcal resistance is increasing, clinical trials suggest that
amoxycillin still remains adequate treatment for pneumonia, as drug levels still
exceed the MIC levels of the resistant organism (less than 5% of pneumococci
show high level resistance – May 2012).
32
Tuberculosis
•
•
•
•
Tuberculosis is a notifiable disease- notify to Medical Officer of Health ext 2065
Treatment of tuberculosis is a specialised area and should involve respiratory
physician and public health input to ensure adequate treatment and contact tracing
occurs.
Liver function, serum creatinine, electrolytes, are essential blood tests that should
be checked before treatment.
Liver function should be monitored routinely.
Pathogen:
Mycobacterium tuberculosis.
Drug Treatment:
•
•
•
•
Multiple antitubercular drug therapy is initiated primarily to guard against the
existence and/or emergence of resistant organisms.
The current recommendations are for a short course, i.e. Six months of therapy in
pulmonary tuberculosis. Extra-pulmonary Tb often requires longer courses.
This consists of an initial two months of therapy using 3 or 4 drugs, the aim of which
is to obtain a rapid decrease in the number of viable organisms, followed by a
further four months of therapy with 2 drugs, rifampicin and isoniazid, to eradicate
any remaining organisms.
The initial regimen must contain pyrazinamide for the short course to be effective.
DRUG
Rifampicin1
and
Isoniazid 1,2,3
and
Pyrazinamide1
±
Ethambutol 1,4,5,6
DOSE
Wt <50kg, 450mg po mane for 6 months
Wt ≥50kg, 600mg po mane for 6 months
300mg po mane for 6 months
Wt <50kg, 1.5g po mane for 2 months
Wt ≥50kg, 2g po mane for 2 months
15mg/kg po mane for 2 months, or until
sensitivity results return
1
Four drugs are given daily in those with previous TB therapy, those from high
incidence countries and those with extensive disease. i.e. Rifampicin, Isoniazid,
Pyrazinamide and Ethambutol.
2
Combination tablets of Isoniazid and Rifampicin exist in NZ – Rifinah 150 (Rifampicin
150mg/Isoniazid 100mg) and Rifinah 300 (Rifampicin 300mg/Isoniazid 150mg)
3
Pyridoxine 25mg po is usually given daily while on isoniazid to prevent neurotoxicity.
4
Ethambutol (the 4th drug) can be omitted from NZ born patients without prior
treatment.
5
Ethambutol is not recommended for children under 6 years.
6
Visual acuity with a Snellen chart and red-green vision should be checked prior to
commencement of ethambutol and regularly throughout treatment
Treatment Duration:
At least 6 months
Notes:
• Intermittent supervised therapy is often given in twice or three times week regimens
and is preferred for infectious pulmonary tuberculosis.
• Always check dosages (Refer to Guidelines for Tuberculosis Control in NZ 2010)
http://www.immune.org.nz/sites/default/files/factsheets/guidelines-tuberculosiscontrol-new-zealand%202010.pdf
33
Influenza
•
•
•
•
•
•
•
•
•
The typical clinical syndrome caused by Influenza virus infection is an abrupt onset
of fever, myalgia and cough.
Many cases are less typical, however. Most cases of “Influenza – like illness” are
caused by other agents.
Influenza may mimic meningococcal disease – be wary when making a clinical
diagnosis
Influenza usually circulates as a distinct epidemic for 4 to 6 weeks each winter.
Superinfection with bacteria such as Haemophilus influenzae and Staphylococcus
aureus can cause severe pneumonia and these should be covered in empiric
treatment.
Neuraminidase inhibitors such as oseltamivir, if administered early, reduce severity
and duration of illness and reduce viral shedding and may be considered in
specific circumstances. They are not Pharmac funded.
Outbreaks can occur on hospital wards and in long-term care facilities.
Nasopharyngeal swab for direct immunoflourescence is available within Waikato
Hospital. This is available 6 days a week during influenza season. Sensitivity is
60-80%.
Acute and convalescent serology is also available to make a retrospective
diagnosis of influenza.
34
GASTROINTESTINAL TRACT AND
INTRA-ABDOMINAL INFECTIONS
Dental and Gingival Infections
For tooth abscess, inflamed wisdom tooth area or root canal infection, local
treatment includes removal of the dental pulp from the related tooth or extraction of
the tooth, as well as drainage of the abscess when fluctuant.
With mild disease, antibiotics are often not required.
•
•
Pathogens:
Common:
Mixed aerobic and anaerobic oral flora.
Drug Treatment:
DRUG
DOSE
Empiric
Amoxycillin/Clavulanate
500/125mg orally tds
or
Clindamycin1, H
1
300mg orally tds
For patients with penicillin allergy.
Treatment Duration:
3 - 5 days
35
Acute Peritonitis
Pathogens:
Common:
Enterobacteriaceae, Enterococcus, Anaerobes.
Other:
Streptococcus milleri (especially in abscesses).
Drug Treatment:
DRUG
DOSE
Cefuroxime1,2
750mg IV q8 hourly
and
Metronidazole
500mg IV q8 hourly
and if pelvic inflammatory disease
suspected
Doxycycline
100mg PO q12 hourly
Treatment Duration:
5 - 10 days
Notes:
• Consult Specialist to discuss management of patients with severe penicillin allergy.
• Various treatment strategies are suggested in the literature using single, dual and
triple combinations.
• All strategies appear equally effective with the proviso that the drug regimen used
has activity against Enterobacteriaceae and Bacteroides fragilis.
• Cefuroxime covers the majority of Enterobacteriaceae involved in acute peritonitis.
• Abscesses may require longer therapy and/or drainage.
• If a patient has improved clinically on cefuroxime/metronidazole and has had the
underlying cause of peritonitis adequately treated, oral co-amoxyclavulanate can
usually be given to complete a course of antibiotics provided there is no
microbiologic evidence to the contrary.
36
Cholecystitis / Cholangitis
Pathogens:
Common:
Enterobacteriaceae, Enterococcus.
Drug Treatment:
DRUG
DOSE
Gentamicin
See gentamicin dosing guideline
and
Augmentin
1.2g IV q8 hourly2
Patients with mild penicillin allergy or significant renal dysfunction
Ceftriaxone
1g iv 24 hourly
and
Metronidazole
1
500mg iv inf 12 hourly
If IV therapy is still indicated after three days consider augmentin or
piperacillin/tazobactamH 4.5g IV 8 hourly as monotherapy depending on clinical
response.
Treatment Duration:
5 - 10 days
Note:
Consult Specialist to discuss management of patients with severe penicillin allergy.
37
Acute Pancreatitis/Severe Necrotising Pancreatitis
•
•
Antibiotics are not indicated in the initial management of acute pancreatitis.
Antibiotics can be considered on a case by case basis for patients with severe
necrotising pancreatitis (defined by CT) or suspected pancreatic abscess
Pathogens:
Common:
Enterobacteriaceae, Enterococcus, Anaerobes.
38
Infectious Diarrhoea
•
•
•
The first priority in management is to ensure adequate fluid and electrolyte
replacement.
Routine administration of antibiotics is not indicated and may be harmful in
certain situations.
Discuss antibiotic administration with an infectious disease specialist or clinical
microbiologist.
Pathogens:
Common:
Campylobacter jejuni (73%). Salmonella sp (non typhi) (7%), Shigella sp (1%).
Other: (<1%)
Yersinia enterocolitica, Vibrio parahaemolyticus, Plesiomonas shigelloides.
Drug Treatment:
DRUG
Pathogens Known
DOSE
Campylobacter jejuni
Usually self-limiting, routine use of
antibiotics not recommended1
Usually self-limiting, routine use of
antibiotics not recommended2
Metronidazole 2g po daily for 3 days
Usually self-limiting in immunocompetent
host. No role for antimicrobial therapy
Salmonella species (non-typhi)2,3
Giardia
Cryptosporidiosis3
1
Consider therapy if high fever or bloody diarrhoea with Norfloxacin 400mg 12hrly
Treatment may lead to an increased risk of clinical relapse. If treatment required
Ciprofloxacin 500mg 12hrly is usually the treatment
3
Infectious disease consultation in immuno-compromised host, very severe illness or
bacteraemia.
2
Treatment Duration:
Variable.
39
Clostridium difficile disease
•
•
•
Send stool for antigen testing in patients with a diarrhoeal illness occurring
more than 48 hours after hospital admission or with a history of antibiotic use.
5% of Clostridium difficile infection occurs in patients without a history of
antibiotic use and this proportion may rise during hospital-based epidemics.
Do not underestimate the potential for Clostridium difficile to cause severe
disease. In all cases but especially the elderly, provide careful supportive care
with attention to hydration and nutrition.
SEVERE DISEASE
• Use PO or NG vancomycin as a first-line agent in any patient with a clinically
severe illness.
• Severe disease is defined as two or more of: age>60, T>38.3, serum albumin
<25g/L, TWC>15 cells/mL.
DRUG
DOSE
Empiric
Metronidazole
400mg po 12 hourly
or
VancomycinH
125mg po 6 hourly
Treatment Duration:
14 days.
40
Typhoid / Paratyphoid Fever
Pathogens:
Salmonella typhi, Salmonella paratyphi.
Drug Treatment:
DRUG
DOSE
Empiric
AzithromycinH
1g po daily 10 days
or
Ceftriaxone
2g IV daily
Treatment Duration:
5 - 10 days.
Notes:
Salmonella typhi resistance to ciprofloxacin has increased to the point that it is no
longer first line therapy. If patient is still febrile at 5 days suspect resistance.
41
Helicobacter Pylori Infection
Pathogen:
Helicobacter pylori.
•
All patients with positive tests for H.pylori infection should undergo eradication
therapy.
•
For eradication regimes refer to the New Zealand Formulary.
•
Most regimes consist of an acid suppressant such as Omeprazole 20mg bd
along with two antibiotics eg amoxicillin 1g bd and clarithromycin 500mg bd or
amoxicillin 1g bd and metronidazole 400mg tds or clarithromycin 500mg bd and
metronidazole 400mg bd.
•
Test for cure: treatment failure is increasingly recognised and predicts relapse
of ulcer disease. Request H.pylori faecal antigen test one month following triple
therapy – inform patient of the following recommendations and include them in
the discharge summary to GP; i) perform test one month following completion
of eradication therapy, ii) patient must not be taking antibiotics, antacids, or
acid-suppressants in the two weeks preceding the test, iii) re-treat according to
the New Zealand Formulary for patients with positive stool antigen tests.
42
URINARY TRACT INFECTIONS
Urinary tract infection as a clinical entity is a source of considerable confusion, resulting
in significant over-use of antibiotics. The following rules of thumb are used by infectious
disease physicians to aid decision-making:
1. Only pregnant women and patients undergoing genitourinary tract
instrumentation are treated for asymptomatic bacteriuria. In the
absence of symptoms we do not treat bacteriuria in elderly patients,
diabetics, patients undergoing joint arthroplasty, patients with indwelling
urinary catheters or patients with positive assays for leucocytes/nitrites on
dipstick testing.
2. Urinary tract infection is an unlikely cause of delirium in elderly
patients without genito-urinary symptoms or systemic evidence of
sepsis.
3. A “complicated” urinary tract infection is defined by the presence of
underlying conditions that increase the risk of treatment failure (see below).
This does not include acute first episodes of pyelonephritis in healthy young
women with only mild to moderate symptoms.
Cystitis
•
•
•
•
Cystitis is the syndrome of frequency and dysuria in women1.
It is due to bacterial infection in 70-80% of cases.
Patients with bacterial cystitis usually have pyuria.
Men with cystitis should be evaluated thoroughly for sexually transmitted infection
(STI) and structural abnormalities of the male genito-urinary tract.1 Refer to STI
guidelines or treat as “complicated” urinary tract infection if STI ruled out.
Pathogens:
Cystitis in women:
Escherichia coli, Staphylococcus saprophyticus.
Drug Treatment:
DRUG
DOSE
Empiric
Trimethoprim2
600mg po stat, or 300mg po daily for
three days
If resistant to trimethoprim3
Nitrofurantoin
200mg po stat, or 100mg po 12 hourly for
three days
Amoxycillin/clavulanate
500/125mg po 12 hourly
Pathogens Known
Alternatives used according to sensitivities.
1
Urinary tract infections in men are often associated with infection of the posterior
urethra, prostate or epididymis.
2
Avoid trimethoprim and norfloxacin during pregnancy. Amoxycillin/clavulanate
43
3
500/125mg 12 hourly or cephalexin 500mg 12 hourly are suitable alternatives.
Trimethoprim resistance is present in 20% of E.coli but 50% of women with resistant
isolates responding to treatment. Treat women with resistant isolates who have not
already responded to trimethoprim.
Treatment Duration:
3 days
Uncomplicated pyelonephritis
A proportion of non-pregnant young women with clinical evidence of pyelonephritis can
be managed in the community. In this situation, ciprofloxacin 500mg bd is an
appropriate agent even in severe cases (Lancet 2012; 380: 484-90) and is approved
without ID or microbiology approval as follows;
1. The patient has been reviewed or discussed with an Emergency Department
SMO to confirm the diagnosis of pyelonephritis vs cystitis1. The name of the
SMO must be written on the prescription.
2. The patient is female, non-pregnant and has received an intravenous dose of
antibiotic (gentamicin or ceftriaxone)
3. The patient has been able to absorb food and fluids over a period of
observation in the emergency department
4. The patient is accompanied by a competent carer for the first 24 hours of
treatment.
5. The patient and carer have been counselled regarding the need to continue
antibiotics and to re-present to hospital if fever persists beyond 48 hours,
symptoms worsen or vomiting prevents absorption of antibiotics.
1
Patients with cystits (ie frequency and dysuria without documented fever, back pain or
sepsis) should receive treatment according to cystitis guidelines.
44
Complicated UTI
•
Complicated urinary tract is defined by the presence of factors that increase the risk
of treatment failure. This includes;
• Diabetes; pregnancy; renal failure; known obstruction or structural lesions of
the urinary tract; recent instrumentation; indwelling catheter or nephrostomy;
immunosuppression; renal transplant patients; male patients
•
Organ imaging (usually ultrasound or non-contrast CT urogram) should be
considered in the following cases:
• Men with recurrent bacterial cystitis or pyelonephritis
• Patients with bacteraemia or if acute pyelonephritis follows an atypical course
(ie persistent severe toxicity/septic shock despite antibiotics)
• UTIs become closely spaced
• UTIs occur prior to commencement of sexual activity
• Persistent haematuria following resolution of infective symptoms
Pathogens:
Escherichia coli, other coliforms, enterococcus spp, Pseudomonas aeruginosa.
Drug Treatment:
Scenario 1: the patient has a complicated urinary tract infection requiring
admission and no contraindications to gentamicin.
Rx: Gentamicin 5mg/kg; follow gentamicin dosing guidelines.
Scenario 2: the patient has a complicated urinary tract infection with absolute or
relative contraindications to gentamicin (including pregnancy)
Rx: Ceftriaxone 2g daily; check culture and sensitivity results daily
Scenario 3: gentamicin or ceftriaxone have been given for 48 hours and culture
results are available
Rx: Switch to an appropriate oral agent once the patient is clinically improving
Scenario 4: gentamicin or ceftriaxone have been given for 48 hours and there are
no culture results available
Switch to one of the following regimes if the patient is clinically improving and continue
to follow culture results:
•
•
Augmentin 625mg PO 8 hourly
Cotrimoxazole 480mg PO 12 hourly (avoid in pregnancy)
Treatment Duration:
Use IV therapy until satisfactory clinical response, followed by oral therapy when
tolerated for a total of 7 days. Longer courses may be required in the presence of an
abscess, prostatitis or an obstructed urinary tract system. Consult urology or infectious
diseases.
45
Ciprofloxacin prescribing policy
1. Ciprofloxacin is a restricted pharmaceutical
2. Ciprofloxacin will be dispensed in accordance with the “restricted
pharmaceutical policy” and without ID/Microbiology approval in the following
situations
a. Uncomplicated pyelonephritis in women presenting to the emergency
department (see above)
b. Men with suspected prostatitis and cultures proving a ciprofloxacin
susceptible organism
c. Prophylaxis for TRUS biopsy (TRUS to be written on prescription)
d. Treatment of ciprofloxacin susceptible Pseudomonas aeruginosa in a
patient with a clinical diagnosis of complicated urinary tract infection or
respiratory tract infection
e. Other rare scenarios as outlined within this document
46
GENITAL TRACT INFECTION
Genital tract infections usually require more than antibiotic therapy; e.g. full sexual
history, partner tracing, appropriate specimen taking and examination, specialist
knowledge, support, education and counselling. For these reasons, discussion with or
referral to the Sexual Health Service, Health Waikato is recommended.
For discussion or urgent referral, phone ext. 98732 or 98753, or fax referrals to ext.
98892.
Note that the clinic runs on an appointment basis, rather than a walk-in
service. Patients can book their own appointments, on 07 839 8732. The service aims
to see all patients within 48 hours.
47
Pelvic Inflammatory Disease
Pathogens:
Common:
Neisseria gonorrhoea, Chlamydia trachomatis, Enterobacteriaceae, Streptococci sp,
Anaerobes.
Other:
Clostridium perfringens, Group A Streptococci.
Drug Treatment:
DRUG
Inpatient Regimens
A. Cefoxitin
and
Doxycycline3
followed by
Doxycycline3
and
Metronidazole4
B. ClindamycinH
and
Gentamicin
followed by
ClindamycinH, or
Doxycycline3
and
Metronidazole4
DOSE
1,2
2g iv tds
100mg po bd
100mg po bd
400mg po bd
900mg iv tds
2mg/kg loading dose iv followed by
1.5 mg/kg 8 hourly
or 7mg/kg iv daily5
450mg po qds
100 mg po bd
400mg po bd
Outpatient Regimen
Ceftriaxone, or
500 mg im stat
Ciprofloxacin6, H
500 mg po stat
followed by
Doxycycline3
100 mg po bd
and
Metronidazole4
400mg po bd
1
All antibiotic regimens are evidence-based and are of similar efficacy.
2
Patients known to be allergic to one of the suggested regimens should be treated with
an alternative.
3
Avoid doxycycline in pregnancy and children.
4
Metronidazole is included to improve coverage for anaerobic bacteria. Anaerobes are
of relatively greater importance in patients with severe PID and metronidazole may be
discontinued in those patients with mild or moderate PID who are unable to tolerate it.
5
Adjust dosing interval of gentamicin for renal function.
6
Avoid ciprofloxacin in pregnancy and children.
Treatment Duration: 14 days total therapy. In-patient intravenous therapy
should be continued for 24 hours after clinical improvement and then switched to
oral.
48
Bacterial Vaginosis
Pathogen:
Gardnerella vaginalis.
Other:
Mixed anaerobes, e.g. Mobiluncus, Bacteroides,
Mixed aerobes, e.g. Staphylococcus and Streptococci.
Drug Treatment:
DRUG
DOSE
Empiric
Metronidazole
2g po stat or
400mg po 12 hourly for 7 days1
1
If stat treatment is unsuccessful.
Treatment Duration:
See dosage above.
Notes:
•
•
•
G.vaginalis isolation per se should not be treated. Treatment is indicated only with
Gram-stain confirmation of bacterial vaginosis ± symptoms e.g. malodorous vaginal
discharge.
Screen for all other sexually transmitted diseases.
Empirical partner treatment for Gardnerella has no effect on reducing recurrence
rate in women, but it may be advisable to exclude other infections e.g. non-specific
urethritis in sexual partners.
49
Candidosis / Vulvo-Vaginitis
Pathogen:
Candida albicans.
Drug Treatment:
DRUG
DOSE
Empiric
Clotrimazole
500mg pv stat, or
100mg pv nocte for 6 nights
Recurrent infections
Consider monthly therapy with:
ItraconazoleH
or
200mg po 12 hourly for one day
Fluconazole
150mg po stat
Treatment Duration:
See dosage above.
Notes:
• Make sure diagnosis is correct.
• Treating the male partner does not reduce the frequency of recurrences in women;
men should therefore only receive treatment if symptomatic.
• Exclude predisposing factors, e.g. urine dip stick for glycosuria.
• If frequent recurrences (>4 per year), refer to Sexual Health Clinic or combined
Gynae/Skin Clinic for review.
50
Chlamydial Cervicitis / Urethritis
Pathogen:
Chlamydia trachomatis.
Drug Treatment:
DRUG
DOSE
Empiric
AzithromycinH
or
1gm po stat1
Doxycycline2
100mg po bd for 7 days
1
2
Stat treatment is possible due to the long half-life of azithromycinH.
Avoid doxycycline in pregnancy and children.
Treatment Duration:
See dosage above.
Note:
Sexual partners (i.e. within the last 3 months) need to be screened for STDs and
treated for Chlamydia without delay i.e. without waiting for their test results, to avoid
further transmission of infection.
51
Genital Herpes Simplex
Pathogen:
Herpes simplex.
Drug Treatment:
DRUG
DOSE
Empiric
Acyclovir
200mg po 5 times daily
Treatment of superinfection
Cotrimoxazole1
960mg po 12 hourly
1
Avoid cotrimoxazole in pregnancy.
Treatment Duration:
5 days.
Notes:
•
•
•
•
Simple recurrences (secondary attacks) do not always require acyclovir tablets.
Severe HSV infection (e.g. in immunocompromised patients, insulin-dependent
diabetics) may require IV acyclovir.
Suppressive therapy is indicated when confirmed recurrences are frequent (>6-8
per year), severe or associated with significant psychological morbidity – usual
dosage is 400mg po bd.
Consider referral for specialist advice or counselling.
52
Gonorrhoea
Pathogen:
Neisseria gonorrhoea.
Drug Treatment:
DRUG
DOSE
Empiric
Ceftriaxone
500mg im stat
and either:
Doxycycline 1,2
or
100mg po 12 hourly for 7 days
AzithromycinH 2,3
1 g po as a single dose
1
2
Avoid doxycycline in pregnancy and children.
The doxycycline or azithromycinH is given to cover Chlamydia, which co-exists with
gonorrhoea in 40-50% cases. This should be given, even if the Chlamydia test is
negative, as false-negative Chlamydia tests have been reported in this situation.
Treatment Duration:
See dosage above.
Notes:
•
•
•
The incidence of penicillin- resistant Neisseria gonorrhoea means that penicillin or
amoxycillin should be reserved for known penicillin-sensitive strains. Ceftriaxone
(500mg stat IM) is now used due to high rates of ciprofloxacin resistance. If
sensitivity results are known at time of treatment Ciprofloxacin 500mg stat is an
oral alternative.
Pharyngeal and uncomplicated rectal gonorrhoea can be treated successfully with
a single stat dose of ceftriaxone or ciprofloxacin (if the organism is sensitive).
Sexual partners (i.e. within the last 3 months) need to be screened for STDs and
treated for gonorrhoea without delay, i.e. without waiting for their test results, to
avoid further transmission of infection.
53
Non-Gonococcal Urethritis
(Non-Specific Urethritis, NSU)
Pathogens:
Common:
Chlamydia trachomatis, Ureaplasma urealyticum.
Other:
Trichomonas vaginalis, Herpes simplex (less than 5% of cases of NSU)
Various skin bacteria.
Drug Treatment:
DRUG
DOSE
Empiric
Doxycycline1
100mg po 12 hourly for 7 days
or
AzithromycinH
1 g po stat dose
Pathogens Known
Trichomonas vaginalis
Metronidazole
2g po stat
Herpes simplex
Acyclovir
1
200mg po 5 times daily for 7 days
Avoid doxycycline in pregnancy and children.
Treatment Duration:
See dosage above.
Note:
Screen and treat partners as for Chlamydia infection.
54
Trichomoniasis
•
Trichomonas vaginalis causes vaginitis and occasionally urethritis in males.
Pathogen:
Trichomonas vaginalis.
Drug Treatment:
DRUG
DOSE
Empiric
Metronidazole
2g po stat for females or
400mg po bd for 7 days for male contacts
Treatment Duration:
See dosage above.
Syphilis
Pathogen:
Treponema pallidum.
Drug Treatment:
See note below.
Treatment Duration:
Depending on stage of disease.
Note:
The management of syphilis usually requires specialist knowledge.
Therefore
regimens have not been included. Referral to Sexual Health Service, Health Waikato
(07) 8398732 is recommended for people with reactive syphilis serology.
55
SKIN, MUSCLE AND BONE INFECTIONS
•
•
•
•
There is no role for the combined usage of flucloxacillin and penicillin. The
belief that flucloxacillin is able to cover Staphylococcus aureus and not
Streptococcus pyogenes is incorrect.
The MIC90 of flucloxacillin for Streptococcus pyogenes is 0.4µg/ml. This
concentration is extremely easy to achieve. No randomised studies show the
need for both agents http://emj.bmj.com/content/22/5/342.full
If anaerobic cover is required, the use of metronidazole is preferred.
Metronidazole will cover Clostridium tetani if this is being considered.
For suspected bone infections, all efforts should be made to obtain material for
culture before any antibiotics are given to the patient. In the absence of severe
systemic upset it is unlikely that delays for microbial sampling will lead to clinical
deterioration – a definitive microbiologic diagnosis is of the greatest value to
the patient.
Osteomyelitis - Acute
Pathogens:
Common:
Staphylococcus aureus (> 80%), Streptococci species.
Other:
Enterobacteriaceae, Pseudomonas aeruginosa.
Drug Treatment:
DRUG
DOSE
Empiric
Flucloxacillin
Patients with mild penicillin allergy
Cephazolin
2g iv 6 hourly, then 1g po 6 hourly
1g iv 6 hourly
Patients with severe penicillin allergy
ClindamycinH
450mg iv inf 8 hourly, then
450mg po 8 hourly
Treatment Duration:
• Minimum duration is 6 weeks in adults.
• IV therapy should be given for 14 days in adults and then changed to oral
therapy. Children with acute osteomyelitis can be treated with very brief IV
courses (suggested by some authorities as a minimum of 3 days).
Notes:
•
•
Chronic osteomyelitis diagnosis and treatment - refer Specialist.
MRSA osteomyelitis - seek Infectious Diseases advice.
56
Septic Arthritis - Non Prosthetic Joint
Pathogens:
Common:
Staphylococcus aureus, Group A streptococcus.
Other:
Neisseria gonorrhoea.
Drug Treatment:
DRUG
DOSE
Empiric
See empiric therapy for Osteomyelitis
Treatment Duration:
Duration of total treatment is 4 weeks, including at least 7 days IV therapy.
Notes:
•
•
Joint washout usually required - refer Specialist.
Prosthetic joint infections - refer Specialist.
Septic Arthritis - Prosthetic Joint
The proportion of prosthetic hips that become infected is 0.5-1%, knees 1-2% and
elbows 4-9%. Treatment always involves a combination of surgery and antibiotics;
antibiotics are seldom successful when used alone. If possible all antibiotic therapy
should be withheld until appropriate diagnostic samples have been collected.
Eradication of infection is most likely to be achieved if the prosthesis and all
associated foreign material are removed, together with devitalised tissue and
infected bone. Debridement and retention is only recommended as a possibility
in early infection (<3 months after primary implantation).
57
Bites and Clenched Fist Injuries
Bites and clenched fist injuries can often become infected.
In all cases a patient’s tetanus immunisation status must be assessed.
All bites should be cleaned and debrided and irrigated. Elevation and
immobilisation are recommended.
Not all bites require antibiotic therapy. Antibiotics are usually reserved for serious
bites, especially those more than 4 hours old; involving the hand; or associated
with deep puncture wounds or crush injury.
•
•
•
•
Pathogens:
Usually multiple, including anaerobes, Staphylococcus aureus, Streptococci species,
Pasteurella multocida (cats and dogs) and Eikenella corrodens (humans).
Drug Treatment:
DRUG
DOSE
Empiric
Amoxycillin/clavulanate
500/125mg po 8 hourly
Patients with severe infection
Amoxycillin/clavulanate
1g/200mg iv 8 hourly
Patients with penicillin allergy
Cotrimoxazole1
and
Metronidazole
960mg po 12 hourly
400mg po 12 hourly
or
ClindamycinH alone
1
450mg iv inf 8 hourly or
450mg po 8 hourly
Avoid cotrimoxazole in pregnancy and the elderly.
Treatment Duration:
At least 5 days.
Note:
•
Severe infection or poor response to above regimens may also require surgery.
58
Compound Fractures
The patient with a compound fracture should have their immune status to tetanus
assessed. Prophylaxis or early treatment should be given.
Pathogens:
Common:
Staphylococcus aureus
Drug Treatment:
DRUG
DOSE
1
Empiric
Flucloxacillin2
2g iv 6 hourly, then
500mg po 6 hourly
Patients with mild penicillin allergy
Cephazolin
1g iv 8 hourly
followed by
Cephalexin
500mg po 8 hourly
Patients with severe penicillin allergy
ClindamycinH
450mg iv inf 8 hourly, then
450mg po 8 hourly
The duration of antibiotic treatment in compound fractures should be for 1 to 3 days. If
presentation is delayed (>8 hours), presumptive early treatment should be given for 5
to 7 days, but continued for longer if bone infection is established.
2
If wound soiling or tissue damage is severe and/or devitalised tissue is present,
use amoxicillin/clavulanate 1.2 gm IV 8 hourly instead of flucloxacillin.
59
Cellulitis - Simple
Pathogens:
Common:
Streptococcus pyogenes.
Other:
Staphylococcus aureus, Enterobacteriaceae, anaerobes.
Drug Treatment:
DRUG
DOSE
1
Empiric
Flucloxacillin2
1g po 6 hourly
or
1g iv 6 hourly, then
1g po 6 hourly
Patients with mild penicillin allergy
Cephazolin
1g iv 8 hourly
followed by
Cephalexin
500mg po 8 hourly
Patients with severe penicillin allergy
ClindamycinH
450mg iv inf 8 hourly, then
450mg po 8 hourly
Pathogens Known
Streptococcus pyogenes
Benzylpenicillin
1.2g iv 4 hourly
followed by
Penicillin V
500mg po 6 hourly
Staphylococcus aureus
Flucloxacillin alone
As for empiric treatment
1
As the distinction between Streptococcal and Staphylococcal cellulitis is often difficult
on clinical grounds, empiric therapy is directed against both organisms.
Treatment Duration:
• Usual total duration of treatment at least 5 days, depending on response.
• 2IV therapy should only be used for those who are systemically ill or systemically
well but with a co-morbidity such as peripheral vascular disease, chronic venous
insufficiency or morbid obesity which may complicate or delay resolution of their
infection.
Note:
•
•
There is no role for the combined usage of flucloxacillin and penicillin in any
circumstance.
If anaerobic cover is required, the use of metronidazole is preferred.
Metronidazole will cover Clostridium tetani if this is being considered.
60
Cellulitis - Complicating Ulcer
•
•
Complicating ulcer caused by diabetes, vascular disease.
Usually involves multiple organisms.
Pathogens
Common:
Streptococcus pyogenes, Staphylococcus aureus, Enterobacteriaceae, Anaerobes.
Drug Treatment:
DRUG
DOSE
Empiric
Amoxycillin/clavulanate alone
1g/200mg iv 8 hourly, then
500mg po 8 hourly
Patients with mild penicillin allergy
Cefuroxime
750mg iv 8 hourly
and
Metronidazole
500mg iv inf 8 hourly
followed by
Cephalexin
500mg po 8 hourly
and
Metronidazole
400mg po 12 hourly
Patients with severe penicillin allergy
Gentamicin
See gentamicin dosing guideline
and
ClindamycinH
450mg iv inf 8 hourly
Treatment Duration:
Minimum duration of total treatment is 10 days (longer treatment is often required).
Use IV therapy initially for severe infections.
61
Necrotising Fasciitis or Synergistic Gangrene
•
•
•
•
•
•
Necrotizing soft-tissue infections are characterised by rapidly progressing
inflammation and necrosis of skin, subcutaneous fat and fascia, and sometimes
muscle.
Clinical clues to early recognition are: oedema beyond the area of erythema, skin
vesicles, crepitus, the absence of lymphangitis and lymphadenitis, severe systemic
toxicity and pain out of keeping with clinical findings.
These are severe, life threatening infections. If clinical suspicion or LRINEC
score 6 or more call urgently for surgical help.
Antibiotics do not substitute for adequate debridement and there is no proven role
for imaging – therefore do not delay surgical consultation.
Neither antibiotics nor hyperbaric oxygen substitute for surgical debridement.
Consult infectious disease and intensive care specialties early.
Pathogens:
Common:
Mixed aerobes and anaerobes, including Escherichia coli, Bacteroides fragilis,
Streptococcus pyogenes and Staphylococcus aureus.
Drug Treatment:
DRUG
DOSE
Empiric
Benzylpenicillin
2.4g iv q4h
and
CeftazidimeH
2g iv q8h
and
ClindamycinH
600mg IV q8h
Patients with mild penicillin allergy
MeropenemH
1g IV q8h
Patients with severe penicillin
allergy
CiprofloxacinH
400mg IV q12h
and
ClindamycinH
600mg IV q6h
62
Mastitis / Breast Abscess
Pathogens:
Common:
Staphylococcus aureus (if lactating), anaerobes (if not lactating).
Other:
Diphtheroids.
Drug Treatment:
DRUG
DOSE
Empiric
Lactating
Flucloxacillin
500mg po 8 hourly
Non-lactating
Amoxycillin/clavulanate
500/125mg po 8 hourly
Patients with penicillin allergy
ClindamycinH
450mg po 8 hourly
Treatment Duration:
5 days.
Note:
Failure of symptoms to improve after 2 to 3 days suggests other pathogens or an
abscess, requiring review, surgical drainage and bacteriological examination of the
pus.
63
Wound Infections
POST-OPERATIVE
Local measures such as surgical drainage and irrigation with sodium chloride 0.9% will
usually suffice. Topical antibiotics may cause skin hypersensitivity and the emergence
of resistant organisms, and are not recommended.
For mild to moderate infection with surrounding cellulitis, use:
Flucloxacillin 500mg orally, 6 hourly.
Alternatively, if Gram-negative organisms are suspected or known to be involved, use
Amoxycillin/Clavulanate 500/125mg 8 hourly.
For more severe infections particularly where systemic symptoms are
present, use:
Flucloxacillin 2g IV 6 hourly or
Cephazolin 1g IV 8 hourly.
If Gram-negative organisms are suspected or known to be involved, add Gentamicin
5mg/kg IV daily (adjust dose for renal function, see gentamicin dosing guideline).
Episiotomy Infections
Infection of the episiotomy site is an uncommon occurrence. Overall, only 0.1% of
episiotomies become infected, although this rate increases to 1% to 2% for
episiotomies complicated by third- or fourth- degree extensions.
Management is as per postoperative wound infections where gram-negative organisms
may be involved i.e. Amoxycillin + clavulanate 500/125mg 8 hourly.
Very rarely necrotising fasciitis may occur which requires surgery and management as
per the necrotising fasciitis protocol.
64
EYE INFECTIONS
Blepharitis
•
•
•
Blepharitis is an inflammation of the lid margins.
Lid hygiene is an important adjunct to antimicrobial therapy. Remove crusts with
warm compresses prior to administration of eye drops or eye ointment.
If in doubt about the need for antibiotics seek advice from Ophthalmology.
Pathogens:
Common:
Staphylococcus aureus.
Drug Treatment:
DRUG
DOSE
Empiric
Chloramphenicol
Eye drops 0.5%
1-2 drops in affected eyes(s)
2-3 hourly initially
or
Eye ointment 1%
Applied to the affected eye(s)
6 hourly
250mg po
6 hourly
Patients with lid abscesses
Add to empiric treatment:
Flucloxacillin
Treatment Duration:
At least 7 days
65
Conjunctivitis
Pathogens:
May be mixed, including Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus
influenzae, Group A Streptococci, Neisseria gonorrhoea, Chlamydia trachomatis, viruses.
Drug Treatment:
DRUG
DOSE
Empiric:
Chloramphenicol
Eye drops 0.5%
1-2 drops in both eyes
2-3 hourly initially
or
Eye ointment 1%
applied to both eyes
6 hourly
Pathogens Known
Neisseria gonorrhoea 1
Ceftriaxone
1 g iv stat or 125mg iv stat in neonate
Chlamydia trachomatis 1
Doxycycline 2
100mg po
12 hourly
1 gm po
stat dose
or
AzithromycinH
1
2
Treat sexual partners for N. gonorrhoea and C. trachomatis infections.
Avoid doxycycline in pregnancy and children.
Treatment Duration:
Non-Chlamydia infections 5 days
Chlamydia infections
3 weeks
66
TRAVELLERS’ INFECTIONS
Malaria
•
•
•
Malaria must be considered in any patient who has visited a malarious area and
presents with a febrile illness.
Malaria treatment can be complex in some circumstances (critical illness, pregnant
or splenectomised patients, issues of anti-malarial drug resistance etc.).
Involve an infectious disease specialist in the patient’s care and follow-up.
Pathogens:
Common:
Plasmodium falciparum, Plasmodium vivax
Other:
Plasmodium ovale, Plasmodium malariae, Plasmodium knowelsi
Diagnosis and Decision to Admit
• Thick and thin blood films together with a blood sample collected into an EDTA tube
should be sent to the laboratory for examination. A single negative blood film does
not exclude the diagnosis of malaria, particularly if antimalarials or antibiotics have
been taken recently. Patients with exposure and an intermittent fever should be
admitted and serial (usually up to three) EDTA samples taken during consecutive
febrile episodes for thick/thin film assessment.
• All patients with clinically complicated or laboratory diagnosed Plasmodium
falciparum malaria should be admitted for the first 24 hours of treatment due to the
potential for rapid deterioration.
• Patients with uncomplicated Plasmodium vivax do not need to be admitted but
close follow-up is necessary.
Assessment for complicated disease1
• Complicated malaria is defined clinically - both Plasmodium falciparum and
Plasmodium vivax can cause complicated disease. All patients with complicated
malaria should be admitted to hospital.
• Manifestations of complicated malaria relate to adherence of parasitized RBC to
small blood vessels, leading to microcirculatory obstruction, leakage and organ
dysfunction: >5% parasitized RBC, altered conscious level, respiratory distress,
jaundice, oliguria, vomiting, severe anemia, hemodynamic collapse, acidosis,
hepatic failure.
Drug Treatment:
DRUG
DOSE
Complicated – treat in HDU/ICU2
ArtesunateH
2.4mg/kg iv on admission and repeat at
12 hours and 24 hours, then once daily
until oral therapy is possible.
Follow iv therapy with artemether
+lumefantrine 20+120mg 4 tablets orally
with fatty food or full-fat milk at
0,8,24,36,48 and 60 hours, making a
total adult dose of 24 tablets in 6 doses.
67
Plasmodium falciparum – uncomplicated
Artemether+lumefantrine
or
Atovaquone+proquanil4
20+120mg 4 tablets orally with fatty food
or full-fat milk at 0, 8, 24, 36, 48 and 60
hours, making a total adult dose of 24
tablets in 6 doses
250+100mg tablets, 4 tablets orally with
fatty food or full-fat milk daily for 3 days
Plasmodium vivax
Chloroquine sulphateH, 6
then (once G6PD status available)
1g (4 x 250mg tabs) stat PO, followed by
500 mg PO 6 hours later, then 500mg
PO on days 2 and 3.
6
Primaquine
30mg po, daily with food for 2 weeks
1
http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf
2
IV artesunateH is the preferred treatment for severe plasmodium falciparum infection.
This drug is unregistered. It is now available on-site at Waikato Hospital. It is also
available within Auckland hospital pharmacy department and rapid access by courier
is possible.
4
Malarone [Atovaquone/proguanil (250mg/100mg)] should only be used if they did not
take this medication as prophylaxis.
6
Severe haemolysis may occur with G6PD-deficient patients – check G6PD status
before prescribing
Treatment Duration:
Dependent on Plasmodium species (see above).
68
TREATMENT GUIDELINES FOR
COMMON CONDITIONS IN
PAEDIATRIC PATIENTS
Doses in this section are given in mg/kg/dose. Please note that dosage for children
should never exceed the usual adult dosage.
Cellulitis
Pathogens:
Common:
Streptococcus pyogenes.
Other:
Staphylococcus aureus, Enterobacteriaceae, anaerobes.
Drug Treatment:
DRUG
DOSE
Empiric
Flucloxacillin
25 mg/kg/dose iv
6 hourly
30 mg/kg/dose iv
6 hourly
7. 5 - 15 mg/kg/dose po
4 times daily
Pathogens Known
Streptococcus pyogenes
Benzylpenicillin
followed by
Penicillin V
Treatment Duration:
At least 5 days, depending on clinical course.
Notes:
•
•
Doses in this section are given in mg/kg/dose.
Dosage for children should never exceed the usual adult dosage.
69
Conjunctivitis Neonatorum
Pathogens:
Common:
Neisseria gonorrhoea, Chlamydia trachomatis.
Other:
Staphylococcus aureus, Pseudomonas aeruginosa.
Drug Treatment:
DRUG
DOSE
Empiric
Ceftriaxone
30 mg/kg/dose iv
24 hourly
20 mg/kg/dose po
4 times daily for
2 weeks
Pathogens Known
Chlamydia trachomatis
Erythromycin succinate
Treatment Duration:
7 - 14 days
Notes:
•
•
Doses in this section are given in mg/kg/dose.
Dosage for children should never exceed the usual adult dosage.
Epiglottitis
Pathogens:
Common:
Haemophilus influenzae type b.
Drug Treatment:
DRUG
DOSE
Empiric
Cefotaxime
or
Ceftriaxone
50 mg/kg/dose iv 8 hourly
(max 2g per dose)
100 mg/kg/dose iv stat, then 50 mg/kg daily
(max 2g daily)
Treatment Duration:
7 – 10 days.
Notes:
•
•
Doses in this section are given in mg/kg/dose.
Dosage for children should never exceed the usual adult dosage.
70
Meningitis
Consider dexamexethasone 0.15mg/kg/dose 6 hourly for 16 doses, commencing one
hour prior to antibiotics, if Streptococcus pneumoniae or Haemophilus influenzae
suspected.
Pathogens:
Common:
Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae.
Neonatal: Group B Streptococci, Escherichia coli, Listeria.
Other:
Staphylococcus aureus.
Neonatal: Streptococci, coagulase-negative and positive Staphylococci,
Klebsiella, Enterobacter, Pseudomonas.
Drug Treatment:
DRUG
DOSE
Empiric 0 - 3 Months
Amoxycillin
50-100 mg/kg/dose iv
Age 1 week
Age 2-4 weeks
Age >4 weeks
12 hourly
8 hourly
6 hourly
and
Cefotaxime
50 mg/kg/dose iv
Age 1 week
Age 2-4 weeks
Age >4 weeks
12 hourly
8 hourly
6 hourly
Empiric: >3 Months1
Ceftriaxone
Pathogens Known
Pseudomonas
CeftazidimeH
100 mg/kg/dose iv stat, then once daily
(max 4g/day, 2g/dose)
50 mg/kg/dose iv
Age 1 week
Age 2-4 weeks
12 hourly
8 hourly
Streptococcus pneumoniae 2
Ceftriaxone
100 mg/kg/dose iv stat, then once daily
(max 4g/day, 2g/dose)
and
VancomycinH
15mg/kg/dose iv
6 hourly
(max 3g/day)
Benzylpenicillin 3
60 mg/kg/dose iv
4 hourly
Neisseria meningitidis
Benzylpenicillin
60 mg/kg/dose iv
4 hourly
Haemophilus influenzae
Ceftriaxone
100 mg/kg/dose iv stat, then 50mg/kg/dose iv once
daily
71
1
If organisms are seen on the gram-stain, then therapy may be directed accordingly.
Due to increasing resistance, Health Waikato policy determines that a positive gramstain suggestive of Streptococcus pneumoniae now requires treatment with both
ceftriaxone and vancomycin, until sensitivity results become available.
Use both agents until sensitivity results available, then reduce to ceftriaxone or
benzylpenicillin alone.
3
For penicillin-sensitive organisms.
2
Treatment Duration:
Neonatal:
Group B Streptococci
Meningococcal
Pneumococcal
Haemophilus
21
days, or 14 days after CSF sterilisation,
whichever is longer
14 - 21 days
4 days
7 - 10 days
7 - 14 days
Notes:
•
•
Doses in this section are given in mg/kg/dose.
Dosage for children should never exceed the usual adult dosage.
72
Osteomyelitis - Acute
Pathogens:
Common:
0 -2 months:
2 months-2 years:
>2 years:
Group B Streptococci, Staphylococcus aureus, E. coli.
Staphylococcus aureus, Streptococcus pneumoniae,
Haemophilus influenzae B, Group B Streptococci.
Staphylococcus aureus, Streptococci, E coli.
Other:
Salmonella, anaerobes, fungi.
Drug Treatment:
DRUG
DOSE
Empiric: 0-2 months
Flucloxacillin
25-50 mg/kg/dose iv
Age 1 week
12 hourly
Age 2-4 weeks 8 hourly
Age >4 weeks 4-6 hourly
and
Cefotaxime
50 mg/kg/dose iv
8 hourly
25-50 mg/kg/dose iv
4-6 hourly
50 mg/kg/dose iv
8 hourly
Pathogens Known
Staphylococcus aureus
Flucloxacillin
25-50 mg/kg/dose iv
4-6 hourly
E. coli
Cefotaxime
50 mg/kg/dose iv
8 hourly
50 mg/kg/dose iv
8 hourly
100 mg/kg/dose iv
24 hourly
Empiric: >2 months
Flucloxacillin
and
Cefotaxime
H. influenzae
Cefotaxime
or
Ceftriaxone
Treatment Duration:
4-6 weeks
Oral antibiotics may be commenced after 3-7 days of iv treatment, depending on
clinical course.
Notes:
•
•
Doses in this section are given in mg/kg/dose.
Dosage for children should never exceed the usual adult dosage.
73
Otitis Media – Acute
Prior to commencing antibiotics consider whether antibiotic treatment is actually
needed – in uncomplicated Otitis Media watchful waiting has a high success rate
without the side effects of antibiotics.
Pathogens:
Common:
Streptococcus pneumoniae, Haemophilus influenzae.
Other:
Streptococcus pyogenes, Moraxella catarrhalis, Staphylococcus aureus.
Drug Treatment:
DRUG
DOSE
Empiric:
Amoxycillin
25 mg/kg/dose po/iv
8 hourly
or
Sulphamethoxazole/ trimethoprim
20/4 mg/kg/dose po
12 hourly
or
Amoxycillin/clavulanate
10/2.5-20/5 mg/kg/dose po/iv 8 hourly
Treatment Duration:
5 days
Notes:
•
•
•
With increasing pneumococcal resistance, cefaclor is no longer recommended, as it
is active only against fully sensitive strains.
Doses in this section are given in mg/kg/dose.
Dosage for children should never exceed the usual adult dosage.
74
Periorbital / Orbital Cellulitis
Pathogens:
Common:
Streptococcus pneumoniae, Group A Streptococci, Haemophilus influenzae B,
Staphylococcus aureus.
Drug Treatment:
DRUG
DOSE
Empiric
Flucloxacillin
25 mg/kg/dose iv
6 hourly
and
Cefuroxime
50 mg/kg/dose iv
8 hourly
followed by
Amoxycillin/clavulanate
10/2.5-20/5 mg/kg/dose po 8 hourly
Treatment Duration:
IV therapy for a minimum of 48 hrs, then continue with oral therapy.
Total duration of therapy at least 7 days.
Notes:
•
•
Doses in this section are given in mg/kg/dose.
Dosage for children should never exceed the usual adult dosage.
75
Pharyngitis
Most cases of pharyngitis in preschool children are due to viral infection and do not
require antibiotic treatment.
Before commencing antibiotics obtain a bacterial pharyngeal throat swab. Review
bacterial culture 3-4 days before deciding whether to continue antibiotics for a full
10-day course.
The four diagnostic features suggestive of Streptococcus pyogenes infection are:
•
Fever >38oC
•
Tender cervical lymphadenopathy
•
Tonsillar exudate
•
No cough
Pathogens:
Common:
Viruses, Streptococcus pyogenes.
Other:
Mycoplasma pneumoniae, Haemophilus influenza B, Corynebacterium
diphtheriae.
Drug Treatment:
DRUG
DOSE
Empiric
Penicillin V
15 mg/kg/dose po 3 times daily
or
Erythromycin
10 mg/kg/dose po 6-8 hourly
Treatment Duration:
10 days.
Notes:
•
•
Doses in this section are given in mg/kg/dose.
Dosage for children should never exceed the usual adult dosage.
76
Pneumonia
Most Lower Respiratory Tract infections in children are viral.
Pathogens:
Common:
0-3 months:
3 months:
Group B Streptococci, Staphylococcus aureus, Listeria,
Chlamydia, Gram-negative bacilli.
Viruses, Streptococcus pneumoniae.
Other:
Streptococci, Staphylococcus aureus, Haemophilus influenzae, Mycoplasma
pneumoniae, Klebsiella, Pseudomonas aeruginosa, Mycobacterium tuberculosis.
Drug Treatment:
DRUG
DOSE
Empiric: 0-3 months
Amoxycillin
50 mg/kg/dose iv
and
Gentamicin
2-2.5 mg/kg/dose iv
8 hourly
30 mg/kg/dose iv
4-6 hourly
Penicillin V
15 mg/kg/dose po
6 hourly
or
Erythromycin succinate
20 mg/kg/dose po
6-8 hourly
Age 1 week
12 hourly
Age 2-4 weeks 6 hourly
Age >4 weeks
3 hourly
Empiric: >3 months
Benzylpenicillin
or
Treatment Duration:
7 days.
Notes:
•
•
•
•
•
•
If suspicious of Staphylococcal infections, use flucloxacillin 25 mg/kg/dose iv
6 hourly.
Use erythromycin only if likely penicillin allergy, or mycoplasma pneumoniae
infection suspected.
If severely unwell, use broad-spectrum antibiotic cover e.g. cefuroxime 50mg/kg iv
8 hourly.
Legionella pneumophila is extremely rare in immunocompetent children.
Doses in this section are given in mg/kg/dose.
Dosage for children should never exceed the usual adult dosage.
77
Pyelonephritis
Pathogens:
Common:
E. coli, Proteus sp., Klebsiella.
Other:
Staphylococcus aureus, Pseudomonas, Serratia.
Drug Treatment:
DRUG
DOSE
Empiric:
Amoxycillin
and
Gentamicin
1
50 mg/kg/dose iv
6 hourly
7 mg/kg/dose iv
24 hourly, or
2 -2.5 mg/kg/dose iv 8 hourly1
Appropriate for children under one year of age.
(See section on Aminoglycoside dosing in children).
Treatment Duration:
10 days.
Notes:
•
•
Doses in this section are given in mg/kg/dose.
Dosage for children should never exceed the usual adult dosage.
78
Urinary Tract Infections
Pathogens:
Common:
E. coli , Proteus sp., Klebsiella.
Other:
Staphylococcus aureus, Pseudomonas, Serratia.
Drug Treatment:
DRUG
DOSE
Empiric:
Sulphamethoxazole/trimethoprim
12.5/2.5-25/5 mg/kg/dose po twice daily
or
Cefaclor
10-15 mg/kg/dose po
8 hourly
Pathogens Known
As per sensitivities
Treatment Duration:
7-10 days, followed by chemoprophylaxis (dependent on organism) while awaiting
renal investigations, or if otherwise indicated.
Notes:
•
•
Doses in this section are given in mg/kg/dose.
Dosage for children should never exceed the usual adult dosage.
79
Aminoglycoside Dosing In Children
The Paediatric Department has moved to use “extended interval dosing” of
aminoglycosides in children over one year of age. For children, extended interval
usually means once daily dosing. Neonates, children under one year and patients with
infective endocarditis have been excluded. Gentamicin is given at a dose of
5 mg/kg/day IV over 10-15 minutes.
Monitoring Of Aminoglycoside Levels
8 Hourly Dosing Regimens
When treating patients >3 months of age with normal renal function and who are on
concurrent antibiotics (for synergy), peak/trough levels need not be done routinely.
Peak concentrations are of no benefit if drug is infused over >1 hour.
•
Indications for Peak/Trough Levels:
-
•
Age <3 months
Critically ill
Patients receiving concurrent nephrotoxins
Pneumonia, cystic fibrosis
No clinical response after >24 hours of appropriate doses
Burns
Indications for Trough Levels:
- Patients receiving unusually high doses (>3 mg/kg/dose)
- Renal failure
- After 5th dose, if concerned about potential nephrotoxicity.
(Also obtain baseline serum creatinine and repeat on days 5-7 of therapy).
•
-
Indications for Additional Trough Concentrations:
Dose adjusted
Treatment duration >10 days
Additional nephrotoxic drugs being used
Renal insufficiency
High MIC isolate
24 Hourly Dosing Regimens
There is no need to measure peak concentrations.
Concentrations may be measured at 8 hours (or 10 hours) post dose.
If >3.5 µg/ml at 8 hours (or >2 µg/ml at 10 hours), then decrease dose.
80
Dosage Schedules Of Antimicrobial Drugs Used In Paediatric Patients
Note that amounts recommended are mg/kg per dose. Do not exceed recommended dose for adults.
Drug
Penicillins
Penicillin G, crystalline
Penicillin G, procaine
Penicillin V
Flucloxacillin
Amoxycillin
Amoxycillin
Amoxycillin/clavulanate
Route
Mild to Moderate Infections
Severe Infections
PiperacillinH
Piperacillin/tazobactamH
Ticarcillin/clavulanateH
IV/IM
IM
PO
PO/IV
PO
IV
PO
IV
IV
IV
IV
25 mg/kg 6 hourly
25-50 mg/kg 12-24 hourly (max 2.4g/day)
5-12.5 mg/kg 6-8 hourly
12.5-50 mg/kg 6 hourly
7.5-15 mg/kg 8 hourly
Inappropriate
7.5-15 mg/kg 8 hourly
7.5-15 mg/kg 8 hourly
Inappropriate
Inappropriate
Inappropriate
50 mg/kg 4-6 hourly (max 12g/day)
Inappropriate
Inappropriate
50 mg/kg 4-6 hourly
Inappropriate
50 mg/kg 4 hourly
Inappropriate
7.5-15 mg/kg 8 hourly
50 mg/kg 6 hourly or 100 mg/kg 8 hourly
Cephalosporins
Cephalothin
Cephazolin
Cephalexin
Cefoxitin
Cefaclor
Cefuroxime
Cefotaxime
Ceftriaxone
IV/IM
IV/IM
PO
IV/IM
PO
IV/IM
IV/IM
IV/IM
10-20 mg/kg 6 hourly
10-15 mg/kg 8 hourly
6-12.5 mg/kg 6 hourly
Inappropriate
10-15 mg/kg 8 hourly
Inappropriate
Inappropriate
Inappropriate
40 mg/kg 4 hourly
25 mg/kg 6 hourly
Inappropriate
25 mg/kg 4-6 hourly
Inappropriate
50 mg/kg 6-8 hourly
50 mg/kg 6 hourly
50-100 mg/kg 12-24 hourly,
(max 2g/dose or 4 g/day)
Dosage Schedules Of Antimicrobial Drugs Used In Paediatric Patients, cont.
Drug
Carbapenems
MeropenemH
Route
Mild to Moderate Infections
Severe Infections
IV
Inappropriate
20-40 mg/kg every 8 hours
IV
Inappropriate
5 mg/kg 6-8 hourly
PO
PO
PO
PO
7.5-12.5 mg/kg 6 hourly
7.5-12.5 mg/kg 6 hourly
7.5-12.5 mg/kg 6 hourly
7.5-12.5 mg/kg 6 hourly
Inappropriate
Inappropriate
Inappropriate
Inappropriate
IV/IM
PO
5-10 mg/kg 6 hourly
5-10 mg/kg 6 hourly
10-20 mg/kg 6 hourly
Inappropriate
Glycopeptides
VancomycinH
IV
Inappropriate
15 mg/kg 8 hourly (max 500 mg/dose)
Aminoglycosides
Gentamicin
TobramycinH
IV/IM
IV/IM
Inappropriate
Inappropriate
5-7 mg/kg 24 hourly
5-7 mg/kg 24 hourly
IV
PO
PR
PR
5-10 mg/kg 8 hourly
5-10 mg/kg 8 hourly
1-5 years: 250 mg/kg 8 hourly
6-12 years: 500 mg/kg 8 hourly
10 mg/kg 6 hourly
10 mg/kg 6 hourly
Macrolides
Erythromycin
lactobionate
Erythromycin base
Erythromycin ethyl succinate
Erythromycin stearate
Erythromycin estolate
Lincosamides
ClindamycinH
Nitroimidazoles
Metronidazole
82
GUIDELINES FOR
EFFECTIVE USE OF
ANTIMICROBIAL
DRUGS
INFORMATION ON SELECTED ANTIMICROB
DRUGS
Most conditions requiring antimicrobial treatment can be managed using esta
drugs. This is reflected in the recommendations made in the body of this bookle
comments (not intended to be comprehensive) are made on the various cla
antibacterial, antiviral and antifungal agents.
83
Antibacterial Drugs
Beta-Lactams
Penicillins, cephalosporins including cephamycins, monobactams and the
carbapenems, are structurally related and share bactericidal activity primarily directed
at the bacterial cell wall. Most beta-lactams are relatively safe, except in those patients
hypersensitive to them.
Penicillins
Narrow Spectrum Penicillins
These are mainly active against Gram-positive organisms and anaerobes but are
inactivated by beta-lactamases produced by staphylococci and some other organisms.
Benzylpenicillin (penicillin G) is administered parenterally. It still remains the treatment
of choice for a number of infections. Procaine penicillin is an intramuscular preparation
designed to extend the half-life of benzylpenicillin. It provides adequate levels for up to
24 hours but only against highly susceptible organisms. Benzathine penicillin is given
intramuscularly and provides low levels of benzylpenicillin for up to 4 weeks.
Phenoxymethylpenicillin (penicillin V) is acid-stable and thus may be given orally. It is
intrinsically less active than benzylpenicillin.
Antistaphylococcal Penicillins
Flucloxacillin is stable to beta-lactamase produced by staphylococci. Anaerobic activity
is minimal to none, while these agents do not cover enterococci. Flucloxacillin is
reliably absorbed by the oral route, although preferably taken on an empty stomach. It
is generally well tolerated but has recently been found to be associated with cholestatic
jaundice in some patients. This can manifest up to 6 weeks after treatment and may
last for months. It is more commonly seen in elderly patients. This propensity should
not prevent use of this excellent anti-staphylococcal drug in patients with serious
infections.
Methicillin-resistant Staphylococcus aureus (MRSA) should be regarded as clinically
resistant to all beta-lactams, irrespective of laboratory reports of susceptibility.
Conversely, the treatment of choice for methicillin-sensitive Staphylococcus aureus
(MSSA) is a beta-lactam antibiotic, not a glycopeptide. In New Zealand, many MRSA
are not multi-resistant and therapy with macrolides, cotrimoxazole or tetracyclines may
be efficacious (see separate section on MRSA management page 136).
The practice of combining flucloxacillin with penicillin frequently occurs. There is hardly
ever an instance when this is necessary. The belief that you are able to cover
Staphylococcus aureus with flucloxacillin and not Streptococcus pyogenes is incorrect.
Although it is true that the MIC90 of Streptococcus pyogenes to penicillin is 0.015µg/ml,
the MIC90 of Streptococcus pyogenes to flucloxacillin is still excellent at 0.4µg/ml. This
concentration is extremely easy to achieve. No randomised studies show the need for
both agents. If anaerobic cover is required, the use of metronidazole is preferred.
Metronidazole will cover Clostridium tetani if this is being considered.
84
Broad-Spectrum Aminopenicillins
Amoxycillin has greater activity than benzylpenicillin against some Gram-negative
organisms, e.g. Escherichia coli, Haemophilus influenzae but are destroyed by betalactamase producing strains. It is the agent of choice against enterococci.
Antipseudomonal Penicillins
Piperacillin and Ticarcillin (no longer marketed in NZ) are the only penicillins available
that have activity against Pseudomonas aeruginosa. They are more expensive than
most other penicillins.
Beta-Lactamase Inhibitors
Clavulanic acid, and tazobactam inhibit the β-lactamase enzymes produced by
Staphylococcus aureus and Bacteroides fragilis; and also the ubiquitous TEM enzyme,
found in Escherichia coli, Neisseria gonorrhoea and Haemophilus influenzae. They
possess little inherent antibacterial activity, but in combination with penicillins such as
amoxycillin, ticarcillin and piperacillin, they significantly extend their spectrum of
activity. These combinations should be reserved for the treatment of organisms in
which resistance to the beta-lactam antibiotic component is due to enzymes that these
agents can inhibit.
It should be noted that for Pseudomonas aeruginosa, the addition of a beta-lactamase
inhibitor offers no increased activity. The combinations are often more expensive than
the beta-lactam antibiotics alone. Amoxycillin/clavulanic acid can cause diarrhoea and
cholestasis, which occur more frequently than with amoxycillin alone.
Carbapenems
Imipenem/cilastatin, meropenem and ertapenem are available in New Zealand. Due to
inactivation by a renal dipeptidase, imipenem is formulated in combination with the
dipeptidase inhibitor, cilastatin. This preparation has wide activity against enteric
Gram-negative rods and Pseudomonas aeruginosa, comparable to that of
aminoglycosides, and, in addition, has excellent activity against anaerobes including
Bacteroides fragilis, and many Gram-positive organisms. However, it is not active
against MRSA or some strains of Pseudomonas species. These drugs are expensive
and should not be regarded as a first-line agent.
Meropenem is resistant to renal dipeptidase and can therefore be given alone. It also
attains better levels in CSF than imipenem and the risk of seizures is said to be less
than with imipenem. At Waikato Hospital, carbapenems are restricted to the
Haematology/Oncology ward and Intensive Care. Meropenem is currently the major
carbapenem used at Waikato Hospital.
Ertapenem has a narrower spectrum of activity; Pseudomonas and Acinetobacter spp.
are resistant. Its advantage is that it has a long half-life allowing for once a day
administration. Ertapenem is currently on the Waikato Hospital formulary for use with
ESBL infections.
Monobactams
AztreonamH is a member of this family of beta-lactams. This compound is inactive
against Gram-positive organisms and anaerobes but is highly active against the
majority of aerobic Gram-negative bacteria, including beta-lactamase producing
Haemophilus influenzae, enteric Gram-negative rods and Pseudomonas species,
including those resistant to aminoglycosides. It can be given to people with severe
penicillin hypersensitivity, as there is little cross sensitisation. It is expensive and has
so far found little place in treatment of infections within WDHB.
85
Cephalosporins and Related Drugs
For ease of understanding, the cephalosporins have been divided into four classes or
"generations" which reflect their spectrum of activity and price.
Widespread use of cephalosporins has been linked with the increasing prevalence of
infections due to methicillin-resistant Staphylococcus aureus (MRSA), vancomycinresistant enterococci (VRE), drug-resistant Streptococcus pneumoniae (DRSP) and
multiresistant Gram-negative organisms.
First Generation Cephalosporins
Cephalexin / cefaclor / cephradine and cephazolin are “first generation drugs” which
have a similar range of antimicrobial activity. They are active against penicillinaseproducing staphylococci and their Gram-negative spectrum includes Escherichia coli
and Klebsiella species among the enteric Gram-negative rods. They are not active
against Enterococcus faecalis or Listeria monocytogenes. Cefaclor has greater activity
against Haemophilus influenzae and some authorities class this agent as a secondgeneration drug. No first generation cephalosporin has useful activity against the
Gram-negative anaerobe, Bacteroides fragilis, nor against Gram-negative aerobes
such as Serratia, Enterobacter or Pseudomonas.
Second Generation Cephalosporins
Cefuroxime is a "second generation drugs" which is more stable to some Gramnegative beta-lactamases. Cefuroxime’s spectrum of activity encompasses methicillinsensitive staphylococcus and the common respiratory pathogens Streptococcus
pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In addition, it exhibits
activity against Klebsiella pneumoniae, Proteus mirabilis and Escherichia coli.
Enterobacter, Pseudomonas and Acinetobacter species are usually resistant.
Cefuroxime is active against fully sensitive Streptococcus pneumoniae and is not as
effective as amoxycillin against intermediate or high-level penicillin-resistant strains.
Cephamycins
Cefoxitin is cephalosporin-like, but in fact, make up a separate class known as
cephamycins. It is resistant to the extended spectrum beta-lactamases of gramnegative organisms.
Cefoxitin is less active against gram-positive organisms,
particularly against Staphylococcus aureus compared to the second-generation
cephalosporins. It has greater activity against Bacteroides fragilis (60% to 70% of
strains have been reported to be susceptible) than second generation cephalosporins.
These drugs have a limited role in therapy and have traditionally been used for
prophylaxis, although metronidazole provides superior cover for anaerobes than
cefoxitin.
Third and Fourth Generation Cephalosporins
Cefotaxime, ceftriaxone, ceftazidimeH, and cefepimeH are "third and fourth generation
drugs" which have an extended spectrum of activity covering the majority of the enteric
Gram-negative rods. Ceftriaxone has a considerably longer half-life than other
members of this group. The activity of these drugs against Bacteroides fragilis is
considerably less than the cephamycins. Third generation cephalosporins are less
active against Gram-positive organisms than are earlier generations. None has
clinically useful activity against enterococci or MRSA. However, unlike earlier
cephalosporins, which do not enter the cerebrospinal fluid (CSF) in therapeutically
useful concentrations, third generation drugs have been effective in meningitis because
of better penetration and higher intrinsic activity. Some organisms, e.g. Serratia,
Citrobacter and Enterobacter species, have inducible beta-lactamases and resistance
can develop during treatment. Combination therapy with an aminoglycoside has been
86
suggested for serious infections with these organisms.
CeftazidimeH and cefepimeH have valuable activity against Pseudomonas aeruginosa,
with cefepimeH having improved gram-positive activity compared with ceftazidimeH.
Both drugs are inactivated by the ESBL enzymes.
Penicillin Hypersensitivity and Cross-Reactivity
Between 1% and 10% of penicillin courses result in manifestations interpreted as due
to hypersensitivity. Anaphylaxis, angio-oedema and urticaria due to immunoglobulin E
(IgE) directed against penicillin-derived antigens occur within 72 hours, often within
minutes.
Later manifestations (non-IgE) include fever, haemolysis and serum
sickness-like reactions, but rashes are by far the most common.
Delayed
hypersensitivity may present up to 14 days after initiation of the antibiotic with erythema
multiforme, toxic erythema or toxic epidermal necrolysis. Unless rashes are urticarial
they may not represent acute hypersensitivity reactions and they may not recur. This is
particularly so with rashes associated with amoxycillin.
Immediate reactions may be serious or fatal, although fatal reactions are usually
associated with parenteral rather than oral routes. Thus, a detailed history of penicillin
reactions should always be sought before a course of penicillin is commenced. A
history of an immediate hypersensitivity reaction (urticaria, angioedema,
bronchospasm, or anaphylaxis within one hour of drug administration) contraindicates
further exposure to penicillin and other beta-lactam drugs apart from aztreonamH
unless desensitisation has been undertaken. Late manifestations are only a relative
contraindication, although rashes, especially if associated with amoxycillin, are much
less predictive of future problems.
Cross-reaction to cephalosporins occurs in 1-8% of penicillin-allergic individuals.
Carbapenem cross-reactivity can also occur at a similar rate to cephalosporins,
whereas aztreonamH cross-reactivity does not occur.
Skin Prick Testing
Skin prick testing for penicillin allergy is not undertaken at Waikato Hospital or in the
Hamilton region. Auckland Hospital Clinical Immunology service do provide testing,
when a good clinical indication is present. Testing is performed with penicillin
metabolites against which most specific IgE is directed: penicilloyl (major determinant);
and penicilloate and penilloate (minor determinants). Negative skin test results using
major and minor determinants reassure patients and carers that the risk of lifethreatening penicillin allergy is negligible.
There is a <0.1% risk of anaphylaxis after penicillin administration to a patient with a
history of penicillin allergy and a negative skin prick test. This is a similar risk to that of
patients who do not have a positive history.
Desensitisation
It is possible to desensitise individuals. Desensitisation is appropriate for patients who
require penicillin treatment who have a history of penicillin allergy with a positive skin
prick test or a history of penicillin allergy when skin prick testing is not available.
If there has been a history of a life-threatening drug hypersensitivity, desensitisation
should be carried out in a hospital setting, with an intravenous line in situ in the patient
and resuscitation equipment available, including oxygen and adrenaline. Heart rate
and blood pressure should be monitored every 15 minutes with continuous observation
of the patient. Intensive Care should be made aware prior to commencing the protocol.
87
Where non-life threatening features (e.g. rash) have occurred, desensitisation may
occur on an outpatient basis with regular observation and telephone contact available,
and with an action plan for hypersensitivity reactions in place.
Protocols are available from the Pharmacy Department who will be involved in making
up the solutions.
The process involves administration of incremental doses of
penicillin – oral followed by IV – given every 15 - 30 minutes. The whole process takes
5 to 6 hours. This process of acute desensitisation is effective and relatively safe. The
first therapeutic dose should be given within 4 hours of the end of the desensitisation
procedure. The state of desensitisation induced does not last longer than the penicillin
course that is administered immediately after the desensitisation process.
Aminoglycosides
Aminoglycosides usage has reduced over the last two decades as toxicity issues have
clarified and alternative antibiotics have become available. For a comprehensive
discussion on their role at Waikato Hospital please go to page 97.
Tetracyclines
Tetracyclines all have a broad spectrum of activity, which includes Gram-positive and
Gram-negative bacteria, Chlamydia, Rickettsia, Mycoplasma, Spirochaetes, some
Mycobacteria and some Protozoa. Their main use is in the treatment of pelvic
inflammatory disease, acne, periodontal disease, exacerbations of chronic obstructive
pulmonary disease, brucellosis, plague, cholera and Lyme disease.
Tetracyclines are contraindicated in pregnancy and lactation and in children <8-12
years of age. Minocycline and doxycycline each have a longer half-life and absorption
is not significantly affected by the presence of food.
Sulphonamides and Trimethoprim
Sulphonamides now have limited use. Sulphamethoxazole in cotrimoxazole, the
combined formulation with the dihydrofolate reductase inhibitor trimethoprim, has in the
past, found widespread use as a broad-spectrum agent, particularly in respiratory and
urinary tract infections. However, the combination is associated with significant serious
adverse effects due to the sulphonamide, especially in the elderly. Given that
trimethoprim alone is highly effective in the treatment of urinary tract infections, the
combination drug should be restricted to the few clinical situations where it is the drug
of choice. These include the treatment and prophylaxis of Pneumocystis carinii
infection, the treatment of Nocardia infection, the treatment of Listeria monocytogenes
infections in patients with penicillin hypersensitivity and treatment of MRSA infections.
Fluoroquinolones
This class of antibiotic has a broad spectrum of antimicrobial activity, good
bioavailability, excellent penetration into tissues, long serum half-lives, and are
generally well tolerated. Their major downfall is the alarming development of
resistance with the use of these agents. They should be reserved for treatment of
infections resistant to other agents or where an oral agent with this particular
antibacterial spectrum is required.
Resistance to these fluoroquinolones has
commonly occurred, especially where they have been widely used, principally in
infections caused by Staphylococcus aureus, Pseudomonas aeruginosa, enteric Gramnegative rods, Campylobacter species and Neisseria gonorrhoeae. Quinolones are
inappropriate for first line empiric therapy of common infections such as cellulitis,
pharyngitis, otitis media, sinusitis, respiratory tract infections, urinary tract infections or
acute osteomyelitis.
88
Norfloxacin is used in the treatment of urinary tract and gastrointestinal infection.
CiprofloxacinH has a wider range of therapeutic activity against Gram-negative bacilli
including Haemophilus influenzae, enteric Gram-negative rods, Pseudomonas
aeruginosa, some Gram-positive cocci, Gram-negative cocci, and various species of
Mycobacteria. They generally have poor activity against streptococci and in general
should not be considered as the preferred therapy of gram-positive infections.
Fluoroquinolone therapy is not advocated as first-line therapy for S. aureus
osteomyelitis.
Because of excellent bioavailability, oral use is the preferred route in most
circumstances and in fact 750mg orally has a preferred pharmacodynamic profile than
400mg iv. Concomitant administration of iron, aluminium, calcium or magnesiumcontaining medicines can significantly reduce the gastrointestinal absorption of orally
administered quinolones. Therefore, a gap of at least two hours should be allowed
between these agents. Dairy foods containing large amounts of calcium will also
reduce absorption.
Quinolones damage the joints of immature animals and therefore should be used with
caution in children under 14 years. Considerable experience in cystic fibrosis has
shown that they can be used safely in the appropriate clinical situation.
The extended spectrum fluoroquinolone moxifloxacin with increased activity against
Streptococcus pneumoniae (including drug-resistant strains) are available in New
Zealand, but are restricted in both the HML and in the community. This drug has
increased activity against Gram-positive bacteria (including streptococci) and wide
activity against Gram-negative aerobes (but inferior to ciprofloxacin against
pseudomonas). It has good activity against anaerobes and most pathogens causing
atypical pneumonia. Resistance is already beginning to be seen with these newer
agents, which may limit their future.
Currently, the role for these newer
fluoroquinolones is extremely limited.
Ciprofloxacin prescribing policy
Ciprofloxacin is a restricted pharmaceutical in New Zealand
Ciprofloxacin will be dispensed in accordance with the “restricted
pharmaceutical policy” and without ID/Microbiology approval in the following
situations only
a. Uncomplicated pyelonephritis in women presenting to the emergency
department (see above)
b. Men with suspected prostatitis and cultures proving a ciprofloxacin
susceptible organism
c. Prophylaxis for TRUS biopsy (TRUS to be written on prescription)
d. Treatment of ciprofloxacin susceptible Pseudomonas aeruginosa in a
patient with a clinical diagnosis of complicated urinary tract infection or
respiratory tract infection
e. Other rare scenarios as outlined within this document
Usage outside these indications requires ID/Microbiology approval.
Macrolides
The macrolides include erythromycin, roxithromycin, clarithromycinH and azithromycinH.
They have a wide spectrum of activity covering Gram-positive cocci, Legionella,
Bordetella, Corynebacteria, Gram-negative cocci, Mycoplasma, Chlamydia and both
Gram-positive and Gram-negative anaerobes. They are not active against Gram89
negative rods. The newer macrolides have more reliable absorption and longer halflives, allowing less frequent dosing. They attain high intracellular concentrations that
confer theoretical benefits in the treatment of intracellular pathogens. They also cause
adverse effects less frequently than erythromycin.
Erythromycin in all of its oral formulations has variable absorption and frequent GI side
effects. The only parenteral formulation, erythromycin lactobionate, frequently causes
pain and phlebitis. Intravenous doses should be administered slowly to minimise local
reactions and also to avoid arrhythmia.
Erythromycin should not be given
intramuscularly.
Several oral preparations are available, including erythromycin base, the stearate, and
the estolate forms. Although the blood levels achieved with these forms vary
somewhat, when the agents are used against very sensitive organisms, these minor
differences are not believed to be clinically significant. Erythromycin ethylsuccinate has
different absorption characteristics to other forms of erythromycin and therefore higher
oral doses are needed to achieve therapeutic effects. 400mg erythromycin as the
ethylsuccinate provides serum concentrations similar to those provided by 250mg
erythromycin as the base, stearate or estolate. Unfortunately no one formulation
seems to cause substantially less GI upset than others. Erythromycin may produce
interactions with other drugs by inhibiting hepatic metabolism via the cytochrome P450
enzyme system. It can also prolong the QT interval. Waikato District Health Board is
now only stocking Erythromycin ethylsuccinate so whenever oral erythromycin is
referred to in this document it is the succinate form.
Roxithromycin is an alternative to oral erythromycin. It has good oral bioavailability and
may cause less gastrointestinal upset than erythromycin, but is slightly more
expensive. It is fully funded on the Pharmaceutical Schedule.
Clarithromycin, unlike other macrolides, has a microbiologically active metabolite. It is
generally suitable for indications similar to those of erythromycin. It has activity against
Mycobacterium avium complex and is used in combination with other agents for the
treatment of this infection in patients with AIDS. It is not fully funded (except under
special authority for specific indications such as Helicobacter pylori).
AzithromycinH has good in vitro activity against a wider range of organisms than
erythromycin. It is more active against Haemophilus influenzae. It has good oral
bioavailability and in particular rapid and sustained uptake by tissues. Once daily
dosage of this drug is generally acceptable. AzithromycinH can be used for the usual
indications of erythromycin and also for Neisseria gonorrhoea and chlamydial genital
tract infections. It is also used for the treatment of cerebral toxoplasmosis in patients
with AIDS. AzithromycinH has recently been used for uncomplicated typhoid fever (Clin
Infect Dis 2004;38:951-957). It is currently fully funded for urethritis and cervicitis due
to Chlamydia trachomatis.
Glycopeptides
VancomycinH and teicoplaninH are effective only against gram-positive organisms.
They play an important role in the treatment of methicillin-resistant organisms and in
treating severe infection with susceptible organisms in patients who are hypersensitive
to penicillin. Glycopeptides are not as effective as Beta-lactam antibiotics in the
treatment of sensitive Staphylococcus aureus. Vancomycin is given by intravenous
infusion over at least 1 hour to avoid producing the "red man syndrome". TeicoplaninH
can be given by intramuscular injection or by slow intravenous injection or infusion.
TeicoplaninH is considerably more expensive (ten times the price), no more efficacious,
with a similar toxicity profile and should only be considered as a second-line agent or
for community IV therapy.
90
Oral Vancomycin should not be used as first line therapy in Clostridium difficile
diarrhoea. It should be reserved for severe cases unresponsive to metronidazole.
Lincosamides
Clindamycin is active against Gram-positive aerobes and most anaerobes. Although
clindamycin has received a great deal of attention as a cause of C. difficile diarrhoea,
this condition is now recognised to complicate almost all antibiotic therapy. It should
be used as a second choice in those who cannot tolerate conventional therapy. It also
has a role to play in the management of Toxoplasma gondii infection. Both oral and
intravenous formulations are available. The oral formulation has 90% bioavailability.
The intravenous formulation is expensive but is rarely required in someone with a
functioning GI tract.
Linezolid
Linezolid is an oxazolidinone. It is effective against Gram-positive organisms including
MRSA, coagulase-negative staphylococci, vancomycin-resistant enterococci, and
penicillin-resistant strains of Streptococcus pneumoniae. Dosing is twice daily.
Myelosuppression is common with prolonged administration and haematology should
be monitored weekly. Peripheral neuropathy has also been seen with prolonged
therapy. The drug is also known to have monoamine oxidase inhibitory activity. It is
available in both oral and IV formulations. It is extremely expensive and is not on the
WDHB formulary or PHARMAC funded. Its usage within WDHB will only be after
discussion with the Infectious Diseases Service. The major value of this new therapy
will probably be in the long-term management of chronic infections with multi-resistant
Gram-positive organisms. Currently, other options usually exist for this indication. A
monitoring programme to avoid adverse reactions has recently been published in
Antimicrob Agents Chemother 2006;50:1599-602.
Nitroimidazoles
Metronidazole has a spectrum of activity that encompass Gram-negative anaerobes
such as Bacteroides fragilis, Gram-positive anaerobes such as Clostridium species and
anaerobic protozoa including Trichomonas vaginalis, Giardia lamblia and Entamoeba
histolytica. Metronidazole is available as an intravenous preparation; however
excellent absorption means that tablets or suppositories can often be used instead.
Metronicazole may cause a disulfiram-like reaction with alcohol. Recommended
dosage for metronidazole is 400mg orally or 500mg IV with a 12-hourly dosing
schedule.
This is based on pharmacokinetic data and minimum inhibitory
concentrations of the pathogens involved, rather than formal clinical studies.
Rifampicin
Apart from its important role as an anti-tuberculous and anti-leprosy agent, rifampicin is
used to eradicate nasopharyngeal carriage of N. meningitidis, H. influenzae and S.
aureus, and as an adjunct to other antibiotics in serious staphylococcal infection.
Rifampicin causes red discoloration of body fluids and occasional influenza-like
symptoms and hepatotoxicity. It interferes with oral contraceptive metabolism.
Antiviral Drugs
Purine Nucleoside Analogues
Aciclovir is active against Herpes simplex virus and to a lesser extent Varicella-zoster
virus. It is the drug of choice for severe infections caused by these viruses.
Intravenous doses should be administered slowly. ValacyclovirH and famciclovir, which
have longer half-lives, are no longer funded in New Zealand.
91
Ganciclovir is used for the treatment of serious cytomegalovirus infections in immunocompromised patients.
Unfortunately, it has dose-dependent bone marrow
suppressive effects. The drug also has demonstrated mutagenicity in mammalian cells
and carcinogenic potential in animals. Solutions for iv infusion must therefore be
prepared in a biohazard cabinet (currently prepared at Waikato Hospital by Baxter).
Neuraminidase Inhibitors
Zanamivir and Oseltamivir can shorten the duration of influenza symptoms by about
one day if commenced within 48 hours of the onset of symptoms. Both drugs are
neuraminidase inhibitors. Zanamivir is produced in a diskhaler format (and should be
used with caution in severe asthmatics) while Oseltamivir is an oral medication. The
advantages of one over the other are still to be clarified by further trials. These agents
are not funded by Pharmac.
Antiretroviral Drugs
The last decade has seen an explosion in the number of anti-retroviral therapies
specific for HIV infection become available. There were seven nucleoside analogue
reverse transcriptase inhibitors (NRTIs), two non-nucleoside reverse transcriptase
inhibitors (NNRTIs), six protease inhibitors, one integrase inhibitor and an HIV fusion
inhibitor currently funded for use within New Zealand as at August 2012. Antiretroviral
prescribing can only be undertaken by named specialist. At the time of publication
only Dr Jane Morgan and Dr Graham Mills were approved to initiate antiretroviral
therapy.
Antifungal Agents
The number of systemic antifungal agents has grown considerably during the last
decade. The newer agents are usually confined to specific infections in the setting of
immunocompromised individuals.
Polyenes
Amphotericin BH is a polyene compound that remains the treatment of choice for most
serious fungal infections having the broadest spectrum of any antifungal compound
currently marketed. The major action of amphotericin BH is to damage the membrane
of fungal cells. It has significant and serious side effects, predominantly renal toxicity.
Consultation with an infectious diseases physician or clinical microbiologist is advised
concerning its use. Liposomal amphotericinH is less toxic but is extremely expensive
(up to $3000 per day dependent on dose used). Evidence of increased efficacy
against fungal infection compared with the standard preparation of amphotericin ΒH is
anecdotal only. It is likely to be used only in extremely exceptional circumstances after
prior use of standard amphotericin ΒH when significant toxicity has occurred and
alternative antifungal agents are not appropriate.
AmphotericinH has a long half-life (up to 15 days). It is initially given once daily,
although once control of fungal sepsis has been achieved, alternate day dosing can be
used. Dosage modifications of amphotericin BH are not required in patients with renal
insufficiency, in keeping with the low renal excretion of the drug.
Hypersensitivity to amphotericinH is common and consists of headache, fever, severe
rigors, chills, malaise, muscle and joint aches, and hypotension. Symptoms subside
within 4 hours after discontinuance. The occurrence of this side effect decreases with
continued therapy.
92
Intravenous hydrocortisone (50-100 mg) and promethazine can be given prior to
commencing the amphotericinH infusion, although the hypersensitivity reactions are, in
part, dose-related. The patients should be closely observed during the first dose, but
daily incrementation of the dose is not necessary. Regular monitoring of serum
electrolytes, renal function and full blood count is essential.
AmphotericinH is usually infused in 500 ml 5% dextrose, although for volume-restricted
patients, amphotericin BH can be given in a concentration of 0.5mg/ml of 5% dextrose.
It is typically infused via a central line as peripheral venous administration may
predispose patients to develop phlebitis because of the irritant effect of amphotericin
BH. IV administration of 0.5 to 1L sodium chloride 0.9% prior to the amphotericin
infusion is strongly recommended. When commencing amphotericinH, a slow infusion
is recommended over 6 hours. If the patient tolerates this for two successive doses
without any evidence of an allergic response occurring, then the infusion can be
shortened down to a 2 - hour infusion for subsequent doses.
AmphotericinH is nephrotoxic, although impaired renal function is generally reversible
after discontinuation of therapy. Irreversible renal damage is rare. One must be
cautious about using amphotericinH in combination with aminoglycosides, vancomycin,
cisplatin or cyclosporin.
Imidazoles
Clotrimazole, econazole, ketoconazole and miconazole are broad-spectrum antifungal
drugs, which are used in mucocutaneous candidiasis, dermatophytosis and tinea
versicolor. Clotrimazole has some activity against trichomonas, and ketoconazole
shampoo is used in the treatment of seborrhoeic dermatitis and dandruff.
Ketoconazole is active against a variety of fungal infections, particularly yeasts. It has
acid-dependent oral absorption (similar to itraconazole) and is not significantly excreted
in the urine. Hepatotoxicity may occur and liver function tests need to be monitored
monthly. It blocks steroid synthesis and may lead to hypoadrenalism and reduction in
testosterone levels. Ketoconazole has significant interactions with other drugs that are
metabolised in the liver by CYP3A4 isoforms of the cytochrome P450 enzymes.
Triazoles
Fluconazole has a narrow spectrum of antifungal activity, and clinical use is usually
limited to treatment of Candida species. It has good tissue penetration, including
penetration into the central nervous system. It is well absorbed following oral
administration.
Itraconazole absorption is increased with acidic drinks and food. Itraconazole has a
similar spectrum to fluconazole, except for increased activity against filamentous fungi
such as Aspergillus species.
Itraconazole has significant interactions with other drugs that are metabolised in the
liver by the cytochrome P450 enzymes. Fluconazole has a lesser effect on the same
pathway.
VoriconazoleH and PosaconazoleH are newer triazole antifungals structurally related to
fluconazole with a spectrum of action similar to itraconazole. They can be used for the
treatment of invasive aspergillosis, and serious infection with Candida species,
Scedosporium species and Fusarium species. VoriconazoleH is available both as oral
and intravenous preparations, with an oral bioavailability of 96%. As voriconazoleH is
eliminated via a cytochrome P450 pathway, the potential for drug interactions is high.
VoriconazoleH is expensive and should be restricted to patients with proven invasive
aspergillosis intolerant or unresponsive to amphotericin ΒH. VoriconazoleH is active
93
against Aspergillus species, Scedosporium apiospermum and Fusarium species.
PosaconazoleH (currently only available in an oral formulation) is active against
Candida and Aspergillus species. It also has activity against Coccidioides immitis,
Fusarium, Histoplasma, Zygomycetes and phaeohyphomycetes.
Caspofungin
CaspofunginH is the first in a new class of antifungal agents called the echinocandins,
which inhibit β-1,3-D-glucan synthesis in the cell wall in a novel way. It is used in the
treatment of invasive aspergillosis in patients who are refractory to or intolerant of other
therapies, such as amphotericinH or voriconazoleH. It is administered by slow IV
infusion. It is not available in oral formulation.
Flucytosine
Flucytosine is a fluorinated pyrimidine analogue, with antifungal properties. It is
available for oral or parenteral use although it is unregistered in New Zealand and
requires a Section 29 application. It is mainly used in a synergistic combination with
amphotericinH against Cryptococcus neoformans. High serum levels, which often
occur with renal impairment, are associated with bone marrow toxicity and monitoring
of serum concentrations is therefore advised.
Terbinafine
Terbinafine is fungicidal for many dermatophytes. It is well absorbed from the gut and
is of value in treating fungal infections of the skin and nail. It should be used with
caution in patients with hepatic diseases. It may be used topically.
94
DOSING, PHARMACOKINETICS AND
PHARMOCODYNAMICS
The pharmacology of antimicrobial therapy can be separated into distinct components.
The first of these is pharmacokinetics, which deals with the absorption, distribution,
metabolism and elimination of antimicrobials. It is these factors that determine the time
course of antimicrobial concentrations in serum and tissues for a given dosing regimen.
Pharmacodynamics, the second component, is concerned with the relationship
between concentration and the antimicrobial effect.
IMPORTANT PHARMACODYNAMIC PRINCIPLES
1.
The minimum inhibitory concentration is the minimum in vitro concentration of
antibiotic required to prevent inoculum growth. The MIC predicts bacteriologic
response to therapy.
2.
Post-antibiotic effect is the recognised in vitro and in vivo inhibition of growth
despite sub-MIC levels of antibiotics. It is recognised that increasing the peak
level of an antibiotic will also increase the post-antibiotic effect. The effect varies
depending on class of antimicrobial agent and pathogen. An example of postantibiotic effect is shown below.
Antibiotic
Beta-lactam
Vancomycin
Aminoglycoside
Quinolone
Staphylococci
3h
4h
3h
3h
Pseudomonas
0h
N/A
6h
6h
3.
The relationship between tissue levels and serum levels. As most infections occur
in tissues and the common bacterial pathogens are extracellular, interstitial fluid
concentrations at the site of infection are the prime determinants of efficacy. Most
tissue sites within the body can be described as having a large capillary surface
area across which antimicrobials diffuse into a relatively small volume of interstitial
fluid. Drug concentrations at these sites will show little lag and therefore antibiotic
levels will be very close to serum concentrations. Some tissue sites such as
blister, pleural, peritoneal and synovial fluids have a lower ratio of surface area to
volume than most other tissues. Concentrations at these sites will therefore lag
behind those in serum, resulting in lower peak concentrations but higher trough
levels.
4.
Two major patterns of bactericidal activity are now recognised. These are termed
"concentration-dependent killing" and "time-dependent killing". An understanding
of these concepts will have a major impact on how antibiotics are prescribed.
Concentration-dependent bactericidal activity is characterised by a greater extent
and rate of bactericidal activity with higher drug concentrations. Figure 1
demonstrates this characteristic. This pattern of killing is observed with the
aminoglycosides, fluoroquinolones, and metronidazole.
95
Concentration
K3
K2
K1
MIC
………………………………….………..………….…..……
Time
Fig 1: Concentration Dependent Bactericidal Activity
Rate of Kill K3 > K2 > K1
Concentration
Time-dependent bactericidal activity is characterised by a saturation of the rate of
killing at concentrations near the MIC. Thus, high concentrations will not kill the
organism faster or more extensively than low concentrations. The duration of exposure
rather than the concentration is the major determinant of the extent of killing. This
pattern of bactericidal activity is seen with beta-lactams, vancomycin, macrolides and
clindamycin. Figure 2 demonstrates this characteristic. Furthermore, animal studies
have revealed that maximal efficacy for an antibiotic with time-dependent bactericidal
activity can be achieved when serum levels are above the MIC for only 60% of the
dosing interval, and as low as 25% for some organisms.
K0
K0
K0
MIC
…………………………………………..……………………..
Time
Fig 2: Time-Dependent Bactericidal Activity
Rate of Kill K0 is constant
The pharmacodynamic characteristics described reveal that the time course of
antimicrobial activity varies markedly for different antimicrobials and can not be based
solely on half-life of the antibiotic or the MIC data for a particular organism.
It is with this in mind that the dosing guidelines for various antibiotics have been
defined. Much of this pharmacodynamic data is relatively new, differing from some of
the traditional dosing approaches used in the past.
96
Gentamicin: Principles of Usage and dosing
Aminoglycosides have previously played a very important role in the management of
infectious diseases. They continue to play a role in empiric therapy (due to their
potency and low levels of resistance), and a small number of other specific indications
where alternatives are not available. Their toxicity profile has lead to a major
reduction in usage in recent years and as a result, specialist advice should be
sought to weigh the risks and benefits of aminoglycoside courses that are longer
than 3 days.
Gentamicin, tobramycinH and amikacinH are active against aerobic Gram-negative
bacilli including Pseudomonas and are amongst the most rapidly bactericidal drugs
available for treatment of aerobic Gram-negative sepsis. Anaerobes are resistant.
Alone they are inactive against enterococci, but in combination with penicillin (or
amoxycillin) are synergistic. Gentamicin plus penicillin (or amoxycillin) is bactericidal
for most enterococci. Although aminoglycosides are active against most staphylococci
and may be life-saving in unsuspected staphylococcal sepsis, they should not be used
alone to treat staphylococcal infections, because resistance commonly develops.
Gentamicin are no longer the aminoglycoside of choice for hospital-acquired aerobic
Gram-negative sepsis, but are still used as the initial empiric therapy until the organism
and sensitivity profile of the organism has been identified. TobramycinH produces
greater in vitro activity than gentamicin against Pseudomonas aeruginosa, but not other
aerobic Gram-negative bacteria and is nine times more expensive.
All aminoglycosides are potentially ototoxic and nephrotoxic, with clinically significant
adverse effects more likely with advancing age or pre-existing renal impairment.
Pharmacodynamic Properties
The aminoglycosides demonstrate a property known as concentration-dependent
killing. Clinical studies have demonstrated that achievement of high peak serum
concentrations of the aminoglycoside relative to the minimum inhibitory concentration
of the micro-organism being treated, is the major determinant of the clinical response to
the aminoglycosides. This optimisation of the Peak : MIC ratio, can best be obtained
by the “extended interval" administration of aminoglycosides, which result in high peak
concentrations of the drug (peak target ~ 20 µg/ml).
In addition to this property of the aminoglycosides, these drugs also demonstrate a
property known as the post-antibiotic effect, which may be defined as a period of time
after complete removal of the antibiotic during which there is no growth of the target
organism. Although "extended interval" dosing of aminoglycosides may result in a
period of up to 12 hours during which there are no detectable serum concentrations of
the drug, this property of the aminoglycosides allows for “extended interval” dosing
without compromising therapeutic efficacy. This has now been confirmed by a large
number of studies.
Drug Toxicity
The major determinant of aminoglycoside-induced renal and ototoxicity is the
accumulation of these agents within both the renal cortex and the perilymph of the
inner ear, respectively. Uptake and accumulation of aminoglycosides into renal cortical
tissue demonstrates saturable kinetics. The saturable feature of these kinetics makes
peak aminoglycoside concentrations irrelevant when considering tissue accumulation
of the drug. Less frequent dosing of aminoglycosides allows for trough levels of the
drug to fall well below the threshold for binding to their tissue receptors. This also
97
allows for the back-diffusion of aminoglycosides from the renal cortex and inner ear
that may theoretically limit drug toxicity. Toxicity may still occur in some cases where
target levels have been adhered to, particularly after prolonged courses and in preexisting renal failure. We stress again that as a result of toxicity issues, specialist
advice should be sought to weigh the risks and benefits of aminoglycoside
courses that are longer than 3 days.
AMINOGLYCOSIDES: DOSING AND MONITORING
Contraindications
• Previous vestibular or auditory toxicity due to aminoglycoside
• Serious hypersensitivity reaction to aminoglycoside (rare)
Precautions, particularly if used beyond three days
• Pre-existing conductive hearing problem or vestibular problem
• Neuromuscular disorders
• Chronic liver disease or cholestasis (bilirubin > 90 micromole/L)
• Chronic renal failure or deteriorating renal function
Alternative agents
• 3rd and 4th generation cephalosporins eg ceftriaxone, ceftazidimeH or cefepimeH
(the latter two are active against Pseudomonas)
• Fluroquinolones eg ciprofloxacinH (not moxifloxacin)
• Carbapenems e.g. meropenemH or ertapenemH (use is restricted for ecological
and stewardship reasons).
Dual agent therapy
• With another active agent for severe Pseudomonal infection
• With penicillin or amoxicillin for endocarditis
Administration
IV infusion over 30 min.
• Neuromuscular blockade may occur with rapid administration.
The standard dose size is 5 mg/kg of “dosing weight”
• “Dosing weight” is “ideal body weight” or an adjusted “obese dosing weight”
(see below).
• Round the dose to the nearest 20 or 40 mg for adults.
• Adjustment within the range 3 – 7 mg/kg may be required for specific patients
(see below).
• An initial stat dose of 5 mg/kg may be given safely to most patients and
subsequent doses adjusted the next day.
The standard dose interval is 24 hr
• In most cases, adjusting the interval is the preferable way to manage dosing.
• Use the nomogram below to adjust the interval.
• Adjustment within the range 16-48 hr may be necessary, guided by monitoring
levels.
• Intervals in multiples of 12 hr are most convenient and foolproof.
• If intervals beyond 48 hr are indicated, change to another agent.
• Renal function is the main determinant of dosing interval.
• 8 hrly dosing may be used in specific situations such as endocarditis synergy
and for neonates, in pregnancy and >20% burns.
• Close monitoring and dose by dose adjustment is required in renal failure (CrCl
< 30mL/min) and alternative agents are preferred.
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Monitoring
Courses over 3 days: consult with infectious diseases specialist as to the
benefits versus risks. Consider monitoring renal function, vestibular and auditory
function. Toxicity (particularly ototoxicity) may occur with long term use even if serum
gentamicin levels are satisfactory.
It is not necessary to measure drug levels if renal function is normal and the course is
< 48 hr.
Frequency of monitoring
• Initial test: after 24-72 hr of treatment
• Long term monitoring: weekly with additional 3 x weekly serum creatinine
• Recheck aminoglycoside levels if renal function improves or declines
significantly.
• Dose adjustment: remeasurement is often useful at 24 – 48 hr intervals until a
stable satisfactory dose is established.
The ideal time to measure levels is 8 – 12 hr post dose but levels between 6 and up to
14 hours post-dose can be used.
• Suitable when renal function is mildly impaired ie CrCl > 30ml/min
• Usually gives a measurable non zero figure.
• Will pick up cases with slow clearance and those with large Vd.
• Minor errors in recording the administration and sampling times won’t severely
affect interpretation.
• Target level 2-7 mg/L, depends on time of sampling relative to last dose. See
nomogram.
Measure peak and trough levels if difficulty is encountered.
• eg unusual Vd or body composition, changing or unpredictable renal function, if
significant drug accumulation is suspected
• Peak sample: 30 min after end of 30 min infusion.
• Target: gent and tobraH 10-20 mg/L, amikacinH 40-60 mg/L
• Trough sample: within 2 hr of next dose.
• Target: gent & tobra < 1mg/L, amikacinH < 4 mg/L
• For 8 hrly dosing, gent & tobra targets are peak: 5-10, trough <2 (4x time this
for amikacinH).
How to adjust doses
• Try for simple, conventional dose sizes and intervals to minimise administration
errors.
• The Clinical Microbiologist or Infectious Diseases Physician is available to
discuss cases.
• First, try to adjust the interval, using the nomogram.
• Second, adjust the dose size if necessary.
• Third, take peak and trough levels if a satisfactory result is not achieved after a
couple of days (sooner if problems are anticipated).
• Fourth, change to an alternative agent if satisfactory levels can’t be readily
achieved.
99
Calculation of Dose Size
•
Use “Ideal Body Weight” (IBW) to calculate the dose, or the actual body weight
(if less than IBW).
IBW (male) = 50kg + 0.9kg for each cm >150cm in height
IBW (female) = 45.5kg + 0.9kg for each cm >150cm in height
•
If an individual is > 20% above IBW, dosing should be based on the obese
dosing weight (ODW) which is calculated: ODW = IBW + 0.4 (Actual BW IBW).
Ideal Body Weight Chart
Height
Males
(kg)
155 cm / 5’2”
55
160 cm / 5’4”
60
165 cm / 5’6”
64
170 cm / 5’8”
68
175 cm / 5’10”
73
180 cm / 6’0”
78
185 cm / 6’2”
82
190 cm / 6’4”
87
195 cm / 6’6”
91
Females
(kg)
50
55
60
64
69
73
78
82
87
Aminoglycoside Starting Doses for Special Cases
Special Cases
Starting Dose for Extended
Interval Dosing (24 – 48 hrly)
mg/kg/day for gent or tobra
For amikacinH, multiply by 4
Neonates incl premature
3
Infants and Children < 10 y
7
10 - 29 y
6
30 - 60
5
> 60 y
4
Endocarditis, Streptococcal
3 (gentamicin only)
and Enterococcal
Determination of Initial Dosing Interval
•
The initial dosing interval is determined from the eGFR.
•
The initial dose interval is then selected according to guidelines below:
Creatinine Clearance
(mL/min)
>60
45-60
30-45
<30
Initial Dosing Interval
5mg/kg for gentamicin and
tobramycinH. AmikacinH doses are 4x
those.
q24 h
q36 h
q48 h
Consider alternative antibiotic.
One stat dose then seek specialist advice.
100
Nomogram for Dose Interval Adjustment
• Start with the time the sample was taken after the most recent dose, read up to
the measured aminoglycoside level and adjust the dose interval to that shown.
• If the measured level is undetectable, next time measure the peak level;
increasing to 7mg/kg may be helpful.
Note: This nomogram may be used for either gentamicin or tobramycinH and is
calibrated for a dose of 5 mg/kg. For amikacinH, multiply plasma concentration and
dose given by 4. Source: Therapeutic Guidelines Antibiotic 13th ed 2006.
101
Vancomycin Dosing
It is now recognised that Vancomycin is a safe drug that has been underdosed over the
last fifty years since its introduction into clinical medicine. The way to assure optimum
dosing is to measure trough levels. Current recommendations are that the target for
trough levels should be 15±5 µg/ml.
The MIC values for most Staphylococcus aureus are 0.5-1 µg/ml and for Enterococci
and Coagulase Negative Staphyloccci may range up to 2 µg/ml. In cases of serious
infection, the MIC should be checked because at levels of 2 or 4 µg/ml vancomycin will
not be so effective.
With MRSA, small moderately resistant subpopulations
(heterogenous Vancomycin Intermediate S aureus, hVISA) may occur, which are
difficult to detect in the laboratory and may result in therapeutic failure. Prolonged,
subtherapeutic vancomycin dosing appears to allow such strains to emerge in an
individual patient during treatment. If the patient does not improve on vancomycin,
repeat cultures should be obtained and the case discussed with the laboratory so the
organism may be sent to a reference laboratory to check for occult resistance.
Fully Vancomycin Resistant Enterococci (VRE) and S. aureus (VRSA) due to VanA or
VanB have MIC ≥ 32 µg/ml. VRE has been recognised in recent outbreaks within
Auckland hospital (2007) and Waikato hospital (2008).
Vancomycin must be given intravenously for systemic infections. It is not absorbed
when given orally and IM injections cause tissue necrosis.
Ototoxic and nephrotoxic effects of this drug are now considered to be minimal and not
related to specific serum concentrations. However, vancomycin appears to potentiate
the ototoxicity and nephrotoxicity of aminoglycosides. Careful monitoring is required
when administering vancomycin together with an aminoglycoside or other drugs that
are known to be cause ototoxicity or nephrotoxicity.
Usual Dose
The usual adult starting dose is 1.5g for those with creatinine clearance >90 mL/min
and 1.0g for those with creatinine clearance <90mL/min. The dosing interval is usually
12 hourly, but less frequent administration is used in those with renal impairment.
Vancomycin should be infused slowly over at least one hour to avoid anaphylactoid
reactions and the ‘red man’ syndrome.
Dosing Interval
As vancomycin is cleared solely by the kidney, an assessment of the patient’s
renal function is required for determining the appropriate dosing interval. The
initial dosage interval will be determined from an estimate of creatinine
clearance.
Creatinine Clearance (ml/min)
Dosing Interval
> 60
20-60
< 20
q12 h
q24 h
Repeat dose when Vanc level is 1020µg/ml
102
Monitoring
•
•
•
•
•
The primary aim of vancomycin monitoring is to ensure that dosing is
adequate.
Peak levels are not performed, since they are not useful in predicting efficacy and
do not predict toxicity.
Trough levels should usually be performed in those who have been on vancomycin
therapy for greater than 72 hours, but earlier measurements may be required in:
- Patients with high (e.g. burn patients) or low (<50ml/min) creatinine clearance.
- Patients receiving concurrent treatment with other nephrotoxic drugs
(e.g. aminoglycosides, amphotericin BH).
- Patients with infections at sites where there is reduced penetration of
vancomycin (e.g. endocarditis, meningitis, pneumonia).
When trough levels are taken, the aim is to maintain a trough level of
15±5 µg/ml.
Trough levels should be drawn immediately before the next dose. If the first
vancomycin level is taken prior to achieving steady state (i.e. after three or four
doses), the trough level may be misleading.
Adjusting the Dose
Dose adjustments should be done in a simple linear way. For example, if the trough
concentration is 8µg/ml, the dose should be adjusted by a factor of 15/8 or 1.9 fold. In
some pateints dose adjustment may result in doses above those recommended for
starting doses. As a general rule, the maximum dose is likely to be less than 2gm 12
hourly. Beware - taking the first trough level too early (prior to achieving steady state)
or through a line diluted with saline may lead to inappropriate interpretation of the
trough level.
Monitoring Renal Function
Check renal function periodically during the therapy, if the duration of therapy exceeds
72 hours. If signs of renal impairment develop, or if drug accumulation occurs, or
trough levels fall too low, the dose must be reassessed.
Metronidazole Dosing
Metronidazole, a nitroimidazole derivative, is a well-established antimicrobial for the
prevention and treatment of anaerobic infections. Despite having a long serum
elimination half-life of about 8 hours (range 6-12 hours), metronidazole has traditionally
been administered every 6-8 hours. It has never been determined that such a
frequency is necessary. Furthermore, dosing metronidazole every 6-8 hours will lead
to drug accumulation after prolonged use, especially if there is liver impairment.
It has been shown that a dose of 500mg every 12 hours is sufficient to maintain serum
concentrations of the drug above the minimal inhibitory concentration (MIC) of most
anaerobic pathogens for the duration of the dosing interval. There is also some limited
data to suggest that metronidazole may have a post-antibiotic effect against certain
anaerobic bacteria. Metronidazole’s bactericidal activity is based on concentrationdependent killing. All dosing recommendations in this booklet are based upon daily or
twelve hourly dosing of metronidazole. Metronidazole has excellent oral bioavailability
(95-100%) and the iv route should only be used when oral or rectal administration is
not possible.
103
Beta-Lactam Dosing
Beta-lactam antibiotics are frequently given in inappropriately high dosages. The
treatments of meningitis and endocarditis are the only indications for "high" dosage, as
serum levels may not necessarily reflect levels in the infected tissue. For most other
infections, the magnitude of the peak level is no longer deemed relevant. Timedependent killing means that the time above the MIC is the determinant of success.
Examples of this would include ceftazidimeH for a sensitive Pseudomonas aeruginosa
where 1g 8 hourly is more than adequate and ceftriaxone for systemic gram-negative
infections where 1g 24 hourly is satisfactory.
104
IMPAIRED RENAL FUNCTION
Renal impairment may lead to the accumulation of toxic levels of antimicrobial drugs
and/or their metabolites. The following table contains dosage recommendations for
common antimicrobials.
To make best use of the recommendations in the following table, it is necessary to
calculate creatinine clearance (CrCl) as an estimate of glomerular filtration rate (GFR).
eGFR using the CKD-EPI formula since March 2013.
The CKD-EPI formula will not accurately predict clearance in patients with rapidly
changing renal function.
In the presence of diminished renal function, doses may be altered by reducing the
dose or by extending the interval between doses.
Legend For Dosage Guidelines
(See following tables)
1
Method of dosage adjustment:
D = Dose adjustment
I = Dosage interval adjustment.
2
Monitoring of levels recommended to determine precise dosage requirements.
3
Dosage for intraperitoneal administration.
4
Dosage in mg/L of filtrate removed.
5
nd = no data.
6
n/a = not applicable.
7
No supplement means that the dose given is the same as for GFR< 12 ml/min.
8
Dose after means that the dose given is the same as for GFR < 12 ml/min and it
should be withheld until after dialysis on days of dialysis.
*
+
Agents (often) used in combination, see also companion agent
Monitor for myelosuppression
HAEMO Intermittent Haemodialysis
CAPD
Continuous Ambulatory Peritoneal Dialysis
105
Antimicrobial Therapy In Patients With Impaired Renal Function (i)
Drug
Aciclovir
AmikacinH
Amoxycillin
Amoxycillin/
Clavulanate
AmphotericinH
AzithromycinH
AztreonamH
Benzylpenicillin
Cefaclor
CefepimeH
Cefotaxime
Cefoxitin
CeftazidimeH
Ceftriaxone
Cefuroxime
Cephalexin
Cephalothin
Cephamandole
Cephazolin
Chloramphenicol
ChloroquineH
Dose
Adjustment for Renal Failure by GFR (ml/min)
Adjustment > 50 ml/min 10 - 50 ml/min
< 10 ml/min
Method2
D&I
8 hourly
12-24 hourly
50% 24-hourly
D&I
50-100%
50% 24 hourly2 to
30% 48 hourly2
2
30% 48 hourly
I
6-8 hourly
8-12 hourly
24 hourly
D&I
normal
8-12 hourly
50% 12 hourly
D
D
D
D
I
I
D&I
I
I
I
I
I
D
normal
normal
normal
normal
normal
normal
6 hourly
8 hourly
8-12 hourly
normal
normal
6 hourly
6 hourly
6 hourly
8 hourly
normal
normal
normal
normal
50-75%
75%
normal
50% 12 hourly
12 hourly
8-12 hourly
12-24 hourly
normal
normal
6 hourly
6-8 hourly
6-8 hourly
12 hourly
normal
normal
normal
normal
25%
20-50%
normal
25% 24 hourly
24 hourly
24 hourly
50% 24 hourly
normal
50% 24 hourly
8-12 hourly
12 hourly
12 hourly
24 hourly
normal
50%
Doses for Dialysis
Supplement for
Supplement or Dose (D)
HAEMO
for CAPD
8
dose after
no supplement7
dose after8,2
15-20 mg/L of dialysate3 (D)2
dose after8
dose after8
dose for GFR 0.2-1
dose for GFR 0.2-1 nd5
no supplement7
no supplement7
dose after8
dose after8
dose after8
dose after8
dose after8
dose after8
dose after8
normal
dose after8
dose after8
dose after8
dose after8
dose after8
no supplement7
no supplement7
no supplement7
no supplement7
no supplement7
no supplement7
dose for GFR 0.2-1 (D)
no supplement7
no supplement7
no supplement7
no supplement7
normal
no supplement7
no supplement7
no supplement7
no supplement7
dose for GFR 0.2-1
no supplement7
no supplement7
Antimicrobial Therapy In Patients With Impaired Renal Function (ii)
Drug
CiprofloxacinH
ClarithromycinH
ClindamycinH
Co-trimoxazole2,+
Dose
Adjustment
Method2
I
D
D&I
Adjustment for Renal Failure by GFR (ml/sec)
> 50 ml/min 10 - 50 ml/min
< 10 ml/min
12 hourly
normal
normal
12 hourly
12-24 hourly
75%
normal
50% 12 hourly
Doxycycline
Erythromycin
Ethambutol
Flucloxacillin
Fluconazole
Flucytosine
Fusidic acid
Ganciclovir+
Gatifloxacin
D
I
D&I
D
I
I
D
normal
normal
24 hourly
6 hourly
normal
6-8 hourly2
normal
12 hourly
normal
normal
normal
24-48 hourly
8 hourly
50%
12-24 hourly2
normal
24-48 hourly
50%
24 hourly
50%
normal
Avoid
50% 24 hourly
(on dialysis)
normal
50-75%
48 hourly
50% 8 hourly
50%
24 hourly2
normal
48 hourly
50%
Gentamicin2
Imipenem/cilastatinH
Isoniazid
ItraconazoleH
Ketoconazole
Mebendazole
Mefloquine
Metronidazole
MeropenemH
Minocycline
MoxifloxacinH
D&I
D&I
D
D&I
-
normal
normal
normal
normal
normal
normal
normal
normal
8 hourly
normal
normal
100% 36-48 hourly
50% 8-12 hourly
normal
normal
normal
normal
normal
normal
50-100% 12 hourly
normal
normal
avoid
50% 12 hourly
normal
normal
normal
normal
normal
normal
50% 24 hourly
normal
normal
107
Doses for Dialysis
Supplement for
Supplement or Dose (D)
HAEMO
for CAPD
8
dose after
250 mg 8 hourly (D)
dose after8
no supplement7
no supplement7
no supplement7
dose after8
no supplement7
no supplement7
no supplement7
dose after8
no supplement7
dose after8
dose after8,2
no supplement7
dose after8
Dose after as per
0.2-1.0ml/sec
dose after8,2
dose after8
dose after8
no supplement7
no supplement7
no supplement7
no supplement7
dose after8
dose after8
no supplement7
no data
no supplement7
no supplement7
no supplement7
no supplement7
no supplement7
no supplement7
nd5
no supplement7
As for 0.2-1.0mL/sec
4-8 mg/L of dialysate3,2 (D)
nd5
no supplement7
no supplement7
no supplement7
nd5
no supplement7
no supplement7
nd5
no supplement7
no data
Antimicrobial Therapy In Patients With Impaired Renal Function (iii)
Drug
Nitrofurantoin
Norfloxacin
Phenoxymethylpenicillin
Piperacillin
TazobactamH
Praziquantel
Pyrazinamide
Pyrimethamine+
Quinine
Rifabutin
Rifampicin
Roxithromycin
Sulphadiazine+
Dose
Adjustment
Method2
I
D
normal
12 hourly
normal
avoid
12-24 hourly
normal
avoid
24 hourly
normal
Doses for Dialysis
Supplement for
Supplement or Dose (D)
HAEMO
for CAPD
avoid
avoid
no supplement7
no supplement7
dose after8
no supplement7
I
normal
8 hourly
12 hourly
dose after8
no supplement7
D
I
I
normal
normal
normal
8 hourly
normal
normal
normal
6 hourly
normal
50%
normal
24 hourly
normal
50-100%
normal
Avoid if possible
12 hourly
24 hourly
72 hourly
no supplement7
no data
no supplement7
dose after8
no supplement7
no supplement7
no supplement7
nd5
nd5
no data
no supplement7
no supplement7
no supplement7
no supplement7
no supplement7
nd5
12 hourly
24 hourly
normal
normal
normal
8-12 hourly
normal
normal
normal
Avoid if possible
8 hourly
18 hourly
48 hourly
dose after8
no supplement7
no supplement7
no supplement7
normal
8-12 hourly
normal
50-100%
24 hourly2
normal
12-24 hourly
48 hourly
avoid
normal
50% 24 hourly to
30% 48 hourly2
normal
24-48 hourly
48 hourly
avoid
normal
30% 48 hourly2
no supplement7
avoid
dose after8
dose after8,2
no supplement7
avoid
normal
3-4 mg/L of dialysate3 (D)2
Sulphamethoxazole*,+
I
H
Teicoplanin
After dose on
day 4 (I)
Terbinafine
I
Tetracycline
I
Tinidazole
TobramycinH, 2
D&I
Trimethoprim
Vancomycin2, H
I
Adjustment for Renal Failure by GFR (ml/sec)
> 50 ml/min 10 - 50 ml/min
< 10 ml/min
108
avoid
dose after8
every 4-10 days no supplement7
no supplement7
no supplement7
HEPATIC INSUFFICIENCY
Although many antibiotics are metabolised in the liver and a few are excrete
significant extent, in the bile, precise guidelines for dosing in hepatic insufficie
unavailable. There is no test of hepatic function, equivalent to creatinine cleara
renal insufficiency, on which to base dosage adjustments. It is prudent to avoi
with known hepatotoxicity when possible in those with hepatic failure.
For manufacturer’s recommendations consult www.medsafe.govt.nz
109
OBESE PATIENTS
Antibiotic dosing is routinely adjusted for weight, but does not often take account of the
variable proportions of tissues that comprise the body’s mass. The effect of obesity on
the pharmacokinetics of antimicrobials is not very well understood. The volume of
distribution of antibiotics in fat is only about 0.3 to 0.4 that of other tissues. The dosing
weight is therefore often calculated as the ideal body weight plus 0.3-0.4 the difference
between actual and ideal body weight. Since there is likely to be considerable
individual variation, in the case of potentially toxic drugs e.g. aminoglycosides, levels
should be measured and doses adjusted accordingly.
110
PREGNANCY AND LACTATION
Drugs in Pregnancy
During the first 2 weeks of development, the embryo is thought to be resistant to any
teratogenic effects of drugs. The critical period of embryonic development, when the
organ systems develop starts at about 17 days after conception and is complete by 60
to 70 days.
Exposure to certain drugs during this period can cause major birth
defects. However, some drugs can interfere with functional development of organ
systems and the central nervous system in the second and third trimesters and
produce serious consequences.
All drugs should be avoided if possible in the first 12 weeks of pregnancy. If drugs are
to be prescribed, the benefits to the mother and/or foetus must be considerable.
Discrepancies between recommendations on the safety of antimicrobials in pregnancy
are a reminder that all prescribing involves risks and benefits that are often difficult to
quantify. Manufacturers' recommendations tend to err on the side of caution and their
warnings frequently reflect theoretical concerns or insufficient data rather than proven
toxicity.
No antimicrobial is absolutely contraindicated in all circumstances in
pregnancy but the table below may allow choice of a safer alternative or raise the
possibility of deferring treatment.
Refer to the Description of Foetal Risk Categories (below) when prescribing any
antimicrobial medications for women who are pregnant or lactating.
Description Of Foetal Risk Categories
A
Controlled studies show no risk. Adequate, well-controlled studies in pregnant
women have failed to demonstrate risk to the foetus.
B
No evidence of risk in humans. As experience of effects of drugs in this category
in humans is limited, results of toxicological studies to date (including reproduction
studies in animals) are indicated by allocation to one of three sub-groups:
B1
Studies in animals have not shown evidence of an increased occurrence of foetal
damage.
B2 Studies in animals are inadequate or may be lacking, but available data show no
evidence of any increased occurrence of foetal damage.
B3 Studies in animals have shown evidence of an increased occurrence of foetal
damage, the significance of which is considered uncertain in humans.
C
Risk cannot be ruled out. Human studies are lacking, and animal studies are
either positive for foetal risk or lacking as well. However, potential benefits may
justify the potential risk.
D
Positive evidence of risk. Investigational or postmarketing data shows risk to the
foetus. Nevertheless, potential benefits may outweigh the potential risk.
X
Contraindicated in pregnancy. Studies in animals or humans, or investigational or
postmarketing reports have shown foetal risk that clearly outweighs any possible
benefit to the patient. Drugs that have such a high risk of causing permanent
damage to the foetus should not be used in pregnancy or when there is a
possibility of pregnancy (ie avoid in woman of childbearing potential unless
effective contraception is assured).
111
Drugs in Lactation
The benefits of breastfeeding are sufficiently important to recommend that
breastfeeding should be discontinued or discouraged only when there is substantial
evidence that the drug taken by the mother will be harmful to the infant and that no
therapeutic equivalent can be given. Most antimicrobial drugs are only excreted to a
minimal extent in breast milk, and in most cases the dosage to which the infant is
ultimately exposed is very low and is well below the therapeutic dose level for infants.
For this reason there are few antimicrobial drugs that are totally contraindicated whilst
breastfeeding.
112
Antimicrobial Drugs In Pregnancy And Lactation (i)
Drug Category
ANTIBACTERIALS
Penicillins
Use in Pregnancy
(Foetal Risk
Category)
A/B1
Use in Lactation
Safe
Caution high dose IV
Safe
Safe
Caution high dose IV
Safe
Cephalosporins
Beta-lactamase inhibitors
(e.g. clavulanate)
Erythromycin
(Do not use estolate during
pregnancy - increased risk of
maternal hepatoxicity)
ClindamycinH
A/B1
B
Nitrofurantoin
A
Roxithromycin
Aminoglycosides
(Potential for foetal 8th nerve
toxicity)
Chloramphenicol
(Avoid near term - risk of Grey
Baby syndrome)
ClarithromycinH
(Foetal toxicity in primates)
Fusidic acid
Metronidazole and other
nitroimidazoles
(Avoid during first trimester)
B1
D
Safe, monitor infant for
diarrhoea
Avoid in premature infants.
Caution with G6PD
deficiency infants
Safe
Safe
A
Not recommended
B3
Safe
C
B2
Rifampicin
(Neonatal bleeding, give
Vitamin K if used during last few
weeks of pregnancy)
Trimethoprim
(Avoid use in first trimesterteratogenic)
Nalidixic acid
C
Safe
Produces a bitter taste in
milk Withhold breast-feeding
for 24hrs after high dose or
IV
Safe
B3
Safe
A
VancomycinH
Tetracyclines
(Discoloration of teeth, inhibition
of bone growth, maternal
hepatotoxicity)
Sulphonamides
e.g. cotrimoxazole,
sulphamethoxazole
(Avoid near term - risk of
kernicterus)
Fluoroquinolones
e.g. ciprofloxacin, norfloxacin
(Damage to developing
cartilage in animal models)
B2
D
Caution especially in
neonatal period
Safe
Short course is safe
C
Safe
B3
Caution, monitor infant for
diarrhoea
A
A
113
Antimicrobial Drugs In Pregnancy And Lactation (ii)
Drug Category
ANTIFUNGALS
Amphotericin BH
Fluconazole
ItraconazoleH
Ketoconazole
ANTIVIRALS
Aciclovir
Ganciclovir
Antiretrovirals
(Therapy for HIV infection has
not been associated with foetal
risk and prevents transmission.
Expert advice recommended).
Use in Pregnancy
(Foetal Risk
Category)
Use in Lactation
B3
D
B3
B3
Uncertain
Safe
Uncertain
Uncertain
B3
D
Safe
Insufficient data
Contraindicated in HIV positive
women
114
ORAL ANTIMICROBIAL THERAPY
Switch Therapy
The excellent pharmacokinetics and spectra of activity of many oral antimicrobial
agents now enable the physician to choose an alternate approach to the treatment of
infection in selected patients without compromising clinical outcome.
Timely
conversion from intravenous to oral agents has been referred to as switch, step-down
or sequential therapy. This has been shown to be successful in the management of
infections including those of the respiratory tract, skin and soft tissue, and bone and
joint. In addition to reducing the costs of treatment, this approach to the management
of infectious disease can be an important component in the provision of optimal patient
care.
Oral agents are generally much less expensive than parenteral; in addition, hidden
costs such as plasma drug and toxicity monitoring, IV sets and specialised equipment,
nursing and pharmacy time and wastage are avoided. In some patients, the
antimicrobial may be given by mouth from the outset of treatment; this will depend
upon the disease state, its severity and patient characteristics.
Advantages
•
•
•
•
•
Eliminates the risk of adverse events associated with intravenous therapy, such as
phlebitis and increased fluid burden.
Increases patient comfort and acceptance of therapy and permits increased patient
mobility.
Increases the potential for completion of treatment as an outpatient, allowing earlier
discharge from hospital.
Decreases the risk and severity of allergic reactions.
Reduces treatment costs.
Guidelines
Patients eligible for conversion from parenteral to oral therapy should meet the
following criteria:
•
Patient is tolerating oral or NG nutrition or is receiving medication by mouth or NG
tube.
•
Patient has a functional gastrointestinal tract.
•
Signs and symptoms related to the infection have resolved or are improving.
•
Patient does not fall within the parameters of exclusion as described below.
•
Patients should be excluded from immediate consideration for Switch Therapy if
they meet any of the following criteria:
- Patient has an infection in which the continuation of parenteral therapy is
indicated, such as endocarditis, meningitis, line sepsis or Staphylococcus
aureus, or Enterococcus spp. bacteraemia.
- Patient has febrile neutropenia.
Response to oral medication may be unreliable e.g. in the presence of continuous NG
suction, malabsorption syndrome, ileus, protracted vomiting and severe diarrhoea.
Treatment should be reinstated with the original parenteral regimen if continued
improvement in the patient's clinical status is not apparent on oral therapy.
115
Selecting an Appropriate Oral Antimicrobial Drug
The choice of oral antimicrobial agent should reflect the sensitivities of the microorganism(s) involved. In the absence of a cultured pathogen, the oral agent should be
chosen with consideration of the most likely causative organism and its usual
sensitivities. It is not necessary to choose an oral agent from the same antimicrobial
class as the parenteral agent being replaced. The following examples of regimen
conversion are representative only and are not intended to be comprehensive. Doses
will vary according to the clinical circumstances and patient characteristics.
IV Drug and Representative Dose
Amoxycillin
1g q6h
Amoxycillin/
1.2g q8h
clavulanate
Cephazolin
1g q8h
Cefuroxime
750mg q8h
CiprofloxacinH
ClindamycinH
Erythromycin
Flucloxacillin
Gentamicin
Metronidazole
400mg q12h
300-600mg q8h
500-1000mg q6h
1-2g q6h
400mg q24h
500mg q12h
Oral Drug and Representative Dose
Amoxycillin
500mg q8h
Amoxycillin/
500mg q8h
clavulanate
Cephalexin
500mg q8h
Amoxycillin/
500mg q8h
clavulanate
CiprofloxacinH
500-750mg q12h
H
Clindamycin
300-450mg q6h
Erythromycin
800mg q6h
Flucloxacillin
500-1000mg q6h
H
Ciprofloxacin
500mg q12h
Metronidazole
400mg q12h
116
Bioavailability Of Oral Antimicrobials
Drug
Oral
Absorption
(%)
Dose
(mg)
Peak
(µg/ml)
Half-Life
(hr)
Protein
Binding
(%)
Taken
with
Meals
ANTIBACTERIALS
Penicillins
Amoxycillin
Amoxycillin/clavulanate
Flucloxacillin
Penicillin V
60-89
60
50
35-70
500
500
500
500
5.0
4.8
7-14
3-5
1
1
0.5
0.5
17
18
95
35
Yes
Yes
No
No
Cephalosporins
Cephalexin
Cephradine
Cefaclor
90
90
50
500
500
500
15-18
16
13
0.5-1.3
1.3
0.8
5-15
6-20
22-25
Yes
No
No
Fluoroquinolones
CiprofloxacinH
Gatifloxacin
MoxifloxacinH
69-85
96
89
750
400
400
4.0
4.2-4.6
4.5
3-5
7-8
10-14
20-40
20
50
Yes
No
No
Macrolides
Erythromycin base
Erythromycin stearate
18-45
18-45
250
500
0.3-1.0
0.4-1.9
1.4
70-74
Roxithromycin
80
150
6
12
90%
No
Yes
No
100
200
200
250
500
1.8-2.9
3.7-6.7
2-3
1.5-2.2
3.0-4.3
18
93
Yes
11-26
8.5
76
65
Yes
No
600
250
500
160/
800
5.3
5
10
2/40
2.4
6-14
85-94
20
Yes
Yes
11/9
44/
70
Yes
Tetracyclines
Doxycycline
90-100
Minocycline
Tetracycline
95-100
75-80
Miscellaneous
ClindamycinH
Metronidazole
85-90
90-100
Trimethoprim /
Sulphamethoxazole
85-90
ANTIVIRALS
Aciclovir
15-30
200
0.3-0.9
2.2-5.0
9-33
Yes
ANTIFUNGALS
Fluconazole
90
11-12
Yes
Variable
4.5-8
10
3-4.5
24
Ketoconazole
100
200
200
6.5-9.6
84-99
Yes
117
PROPHYLACTIC USE OF ANTIMICROBIAL
DRUGS
SURGICAL PROPHYLAXIS
Appropriate antimicrobial prophylaxis significantly decreases the incidence of postoperative infection following certain surgical procedures. The antibiotic regimen
chosen for these procedures should be directed against the most likely infecting
organism(s) (and not necessarily against every potential pathogen) and be designed so
that the total number of organisms is decreased but not necessarily eliminated. Most
post-surgical infections are due to the patient’s own organisms. In hospitalised
patients, this may include multiresistant organisms, so the following recommendations
may need to be individualised. Prophylaxis is the use of antibiotics to prevent
infections at the surgical site. This must be distinguished from their use in early
treatment, where infection is already established although not necessarily evident
preoperatively (e.g. removal of a perforated appendix).
Major Indications for use of Prophylactic Antibiotics
•
•
Operations in which the risk of post-operative wound infection are high e.g. cleancontaminated surgical procedures.
Operations in which the wound infection rate is relatively low but the consequences
of infection are significant e.g. prosthetic implants.
Principles for timing of Antibiotic Administration
For effective antimicrobial prophylaxis, the drug must be present in the tissues in
adequate concentration at the onset and throughout the operative procedure. To
achieve this goal, the initial dose must be administered parenterally in the immediate
pre-operative period (within 30 minutes) before the operation. Delaying initial dosing
until the post-operative period or giving the antibiotics too far in advance of the
procedure are both associated with an increased wound infection rate. Rectally
administered metronidazole should be given 2 to 4 hours before surgery. VancomycinH
requires a slower infusion that should be completed just prior to induction.
Route(s) of Administration
Intravenous administration is the optimal method to ensure adequate tissue levels
during the operative procedure. In certain instances rectal or oral administration is
appropriate.
Duration of Antibiotic Treatment
The critical period for successful prophylaxis is the 4 hours following implantation of
organisms into a wound. In general, a single dose of parenteral antibiotic is sufficient
118
for most surgical procedures lasting less than 4 hours.
A second dose may be necessary under the following circumstances:
• A delay in starting the operation.
• If the operation is prolonged so that it continues beyond four hours.
• In specific circumstances e.g. amputation of an ischaemic limb.
Giving more than 1 or 2 doses postoperatively is not advised, except where specifically
recommended. Established infection should of course be treated.
Note:
• Prophylactic antibiotics are only one factor that determines the risk of infection.
Other factors of equal or even greater importance are surgical technique, the
duration of surgery, the duration of pre-operative stay, shaving the operation site (if
this must be done, do so immediately pre-operatively), repeat surgical procedure,
obesity, immune compromise and a variety of other host factors (eg diabetes).
• Excessively long courses of 'prophylactic' antibiotic, whether before or after
surgery, select for resistant organisms and may increase the risk of infection. The
practice of continuing prophylactic antibiotics until surgical drains have
been removed is both illogical and of unproven benefit.
Choice of Antibiotic
There are several considerations when selecting an antimicrobial regimen for
prophylaxis:
• Antibiotics should have a spectrum of activity, which includes the pathogens most
frequently responsible for wound infection following a given operation.
• The antibiotics need not be active against every micro-organism present in the
initial bacterial inoculum, as some of the micro-organisms may not contribute to the
development of wound infection.
• Consideration should be given to the serum half-life of the antibiotic and local
hospital antimicrobial susceptibility patterns.
Routine use of vancomycinH prophylaxis is strongly discouraged to prevent selection
pressure for VRE and VRSA. However, vancomycin should replace the cephalosporin
or penicillin component of a regimen when preoperative patients are infected or
colonised with an MRSA strain either currently or in the recent past.
The following tables contain surgical prophylaxis regimens that have been approved for
use by the respective Clinical Directors at Waikato Hospital.
119
Antibiotic Prophylaxis for Surgical Procedures (i)
Type of Surgery
Likely Pathogens
Suggested Regime(s)
GENERAL SURGERY
Contaminated or potentially
contaminated wounds
Abdominal surgery, including upper
and lower GI tract, appendix and
biliary tract and laparoscopic surgery
Anaerobic bacteria, Streptococci,
Aerobic Gram-negative bacilli
Metronidazole (child:12.5mg/kg up to) 500mg IV,
ending the infusion at the time of induction plus
Cephazolin (child: 25mg/kg up to) 1g IV at the time of
induction (2g IV if >80kg). A second dose of cephazolin
is administered for prolonged procedures (greater than
4 hours), or if significant blood loss has occurred
Severe penicillin allergy
Gentamicin 3mg/kg IV (based on lean body mass) and
metronidazole 500mg IV at induction
Clean surgery
Hernia (with prosthetic material),
varicose veins
Staphylococcus aureus, Staphylococcus
epidermidis
Cephazolin 1g IV (2g IV if >80kg) at induction. A
second dose is administered for prolonged procedures
(greater than
4 hours) or if significant blood loss has occurred
Thyroid and Parathyroid surgery
Staphylococcus aureus, Staphylococcus
epidermidis
Flucloxacillin 1g IV at induction.
Breast surgery
Staphylococcus aureus, Staphylococcus
epidermidis
(occasional anaerobes)
Amoxycillin/clavulanate 1g/200mg IV at induction
Note: Not all GI surgery needs prophylaxis. There is no indication for prophylaxis in uncomplicated cholecystectomies in patients younger than 60 as
Antibiotic Prophylaxis For Surgical Procedures (ii)
Type of Surgery
Likely Pathogens
Suggested Regime(s)
VASCULAR SURGERY
Staphylococcus aureus,
Staphylococcus epidermidis
(occasional gram-negative bacilli)
Cephazolin 1g IV (2g IV if >80kg) at induction.
A second dose is administered for prolonged
procedures (greater than 4 hours) or if significant blood
loss has occurred.
LOWER LIMB AMPUTATION
This carries a small but important risk of
clostridial infection.
Use Cephazolin 1g IV (2g IV if >80kg) at induction plus
metronidazole 500mg (child: 12.5mg/kg up to 500mg)
IV ending at the time of induction and then 12 hourly for
24 hours.
CARDIOTHORACIC SURGERY
Staphylococcus epidermidis,
Staphylococcus aureus
Aerobic Gram-negative organisms
Cephazolin 1g IV (2g IV if >80kg) at induction.
A second dose is administered for prolonged
procedures (greater than 4 hours), or if significant blood
loss has occurred.
NEUROSURGERY
Staphylococcus epidermidis,
Staphylococcus aureus
Cephazolin 1g IV (2g IV if >80kg) at induction only.
ORTHOPAEDIC SURGERY
Staphylococcus epidermidis,
Staphylococcus aureus
Cephazolin 2g IV (3g IV if >120kg) at induction only.
Allow 5 minutes to elapse between administration of
antibiotic and application of a tourniquet. A second
dose is administered for prolonged procedures (greater
than 4 hours).
Severe penicillin allergy or patients known to be
colonised with MRSA
Vancomycin 500mg infused over at least one hour
Head And Neck
Mixed anaerobic and anaerobic upper
respiratory tract flora
Amoxycillin/clavulanate 1g/200mg IV at induction
Rhinoplasty +/- cartilage graft
Staphylococcus species
Flucloxacillin 1g IV at induction
Ear or sinus surgery with potential for
dural breach
Mixed aerobic and anaerobic upper
respiratory tract flora
Amoxycillin/clavulanate 1g/200mg IV at induction
Contaminated major ear or sinus
surgery
Mixed aerobes and anaerobic upper
respiratory tract flora
Amoxycillin/clavulanate 1g/200mg IV at induction
EAR, NOSE AND THROAT
SURGERY
121
Antibiotic Prophylaxis For Surgical Procedures (iii)
Type of Surgery
Likely Pathogens
Suggested Regime(s)
OBSTETRIC & GYNAECOLOGICAL
SURGERY
Hysterectomy
Anaerobes, Gram negative bacilli, Group
B Strep, and enterococci
Cephazolin 1g IV (2g IV if >80kg) at induction plus
metronidazole 500mg IV, ending the infusion at the time of
induction.
Severe penicillin allergy
Gentamicin 3mg/kg IV (based on lean body mass) and
Metronidazole 500mg IV at induction or 1g PR 1 hour
pre-operatively.
Caesarean section.
Gram negative bacilli, Group B Strep,
and enterococci
Cephazolin 1g IV (2g IV if >80kg) immediately after
clamping of the cord. The recommendation to delay the
timing of antibiotics, therefore avoiding exposure to the
neonate, may assist in the assessment of potential
sepsis in the neonate. There is no evidence that
Cephazolin given at induction causes either toxicity or
allergy in the neonate.
General
Aerobic Gram-negative bacilli,
Enterococcus faecalis, Staphylococci
Gentamicin 3mg/kg IV (based on lean body mass)
Cystectomy
Aerobic Gram-negative bacilli,
Enterococcus faecalis, Staphylococci
and anaerobes
Gentamicin 3mg/kg IV (based on lean body mass) and
Metronidazole 500mg IV at induction or 1g PR 1 hour
pre-operatively
OPTHALMOLOGY SURGERY
Staphylococcus epidermidis,
Staphylococcus aureus
Cephazolin 1g IV (2g IV if >80kg) at induction only.
There is now evidence that antibiotics
are beneficial for prophylaxis of
wound sepsis as well as endometritis
for all caesarean sections, elective or
nonelective.
UROLOGICAL SURGERY
Orbital Trauma and Orbital Implants
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ENDOCARDITIS PROPHYLAXIS
A revolution in the recommendations for endocarditis prophylaxis has occurred during the last
decade highlighted by the 2007 publication of the American Health Association “Prevention of
endocarditis” guidelines - Circulation 2007;116:1736-1754. These evidence based guidelines are
radically different from previous guidelines and have markedly reduced the indications for
endocarditis prophylaxis acknowledging that the frequency, magnitude and duration of bacteraemia
from dental and other procedures is in fact very similar to that which occurs from everyday activities.
As a result, the need for specific endocarditis prophylaxis around dental and other operative
procedures has been markedly reduced. The Waikato DHB has therefore created new endocarditis
prophylaxis guidelines, adapted from the recommendations made within the AHA guidelines and
2008 NICE guidelines (http://www.nice.org.uk/CG064). The NZ heart foundation guidelines are as
follows. http://www.ttophs.govt.nz/vdb/document/312
Cardiac Conditions associated with the highest risk of adverse outcome from
endocarditis for which prophylaxis is reasonable
• Prosthetic cardiac valve or prosthetic material used for cardiac valve repair.
• Prior episode(s) of infective endocarditis.
• Specific congenital heart disease only
- Unrepaired cyanotic CHD, including palliatie shunts and conduits
- Completely repaired congenital heart defect with prosthetic material or device during the first
6 months after the procedure
- Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or
prosthetic device
• Cardiac transplantation recipients who develop cardiac valvulopathy
• Rheumatic valvular heart disease
Prophylaxis is not reasonable or recommended in any of the following circumstances:
- Native valvular heart disease (except for those with previous infective endocarditis)
- Mitral valve prolapse or hypertrophic cardiomyopathy
- Previous coronary artery bypass graft surgery
- Presence of a cardiac pacemaker
- There is also no role for antibiotic prophylaxis in those with prosthetic joints.
Dental Procedures for which Prophylaxis is reasonable when the above highest risk
cardiac conditions are present
• All dental procedures that involve manipulation of gingival tissue or the periapical region
of teeth or perforation of the oral mucosa.
Endocarditis prophylaxis solely to prevent IE is no longer recommended for any Respiratory, GI or
GU procedures. It is important to state that antibiotic therapy remains important in treating active
infections.
Antibiotic Regimens
Antibiotics are aimed at Streptococcus viridans species.
Standard regimen:
Amoxycillin 2g (children 50mg/kg up to 2g) po 30 to 60 minutes before the procedure.
Patients with penicillin allergy:
Clindamycin 600mg (children 20mg/kg up to 600mg) po 30 to 60 minutes before the procedure.
“Until publication of the recent AHA (Wilson et al. 2007) guidelines, antibiotic prophylaxis was
universally prescribed to cover dental and other interventional procedures in patients at risk of
infective endocarditis (IE). There are, accordingly, a large number of patients with a long history of
taking antibiotic prophylaxis against IE for dental procedures for whom it is no longer considered
appropriate. The information and support needs for such patients are likely to be significant because
they will need to be fully informed about the risks and benefits of antibiotic prophylaxis in order to
make an informed decision not to continue to take it.” NICE guideline comment 2008
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SPLENECTOMY
After splenectomy, people are at risk of severe infection, particularly from a small range of
encapsulated bacteria. About 70% of these post splenectomy sepsis episodes occur in the first 5
years. Adults may be at less risk than children. The most common organisms are Streptococcus
pneumoniae and Haemophilus influenzae type B, with Neisseria meningitidis and S. aureus causing
a few cases only. Malaria is a recognised risk which travellers should be warned about.
Australasian guidelines have been published in Internal Medicine Journal 38 (2008) 349–356.
Prevention of Severe Infections
Measures to prevent severe infections post-splenectomy include:
• Use of spleen-sparing procedures in trauma.
• Vaccination
• Prophylactic antibiotics.
Vaccination(see website for advice)
http://www.immune.org.nz/sites/default/files/resources/ProgrammeFundedPrePostSplenectomy201302
27V03Final.pdf
This should ideally be done 2 weeks before an elective splenectomy.
Post splenectomy, response is believed to be better if given more than 2 weeks after the operation.
Recommended vaccinations include:
•
•
•
•
Pneumococcal 23-valent, 5 yearly. For children, a 13-valent conjugate vaccine is available
which is more efficacious than the 23 valent polysaccharide vaccine.
Haemophilus influenzae Type B. This should be given as per routine schedule for children, but is
unlikely to benefit adults who have a much lower incidence of disease, presumably due to preexisting immunity. This vaccine doesn’t protect against the non-typable H. influenzae, which
causes adult respiratory tract infections.
Meningococcal vaccine. Meningococcal ACYW-135 is recommended. The New Zealand
custom-made serogroup B vaccine is no longer available.
Influenza vaccine seems sensible and could be offered annually.
Prophylactic Antibiotics
Penicillin for “a few years” has been used, but there is no consensus that it is worthwhile, particularly
for adults. There are no guidelines for dose, but amoxycillin has theoretical advantages with better
coverage of Haemophilus and better pharmacokinetics from oral dosing. For the motivated,
informed patient who wishes to use prophylaxis, amoxycillin 250 mg daily (20mg/kg daily for children
<5 years) for 3 - 5 years would be reasonable, although there is no evidence-based literature to
support this. Patient education is vitally important and the following site provides a good resource
for patients. http://www.patient.co.uk/health/preventing-infection-after-splenectomy-or-if-you-do-nothave-a-working-spleen
Treatment Of Post-Splenectomy Sepsis
It would be reasonable for a patient to hold a supply of oral amoxycillin for prompt treatment of
sepsis, but immediate simultaneous presentation to hospital would also be necessary. Ceftriaxone
would be the drug of choice at hospital presentation. Treatment of fulminant sepsis may be
unsuccessful
even
when
initiated
promptly.
125
APPENDICES
OUTPATIENT INTRAVENOUS THERAPY
To ensure the safe and co-ordinated care of a patient who is discharging into the community on IV
therapy the Community Resource Nurse (CRN) must be contacted. (The ward Clinical Nurse Leader
will be able to do this). Nursing policies related to community IV therapy exist within the following
link
http://ourintranet/WDHB/Nursing+and+Midwifery/IV+Therapy+Medicine+Management/Discharge+Pl
anning.htm
Sections within this link include:
How to Discharge Home Your Patient on IV Therapy - Procedure to discharge into the community
on long term intravenous antibiotic therapy
Elastomeric Infusor Order Forms - Waikato infusor order form and Elastomeric infusor information
The CRN will facilitate discharge planning. There are 23 District Nurses based within WDHB, and
all are able to manage IV therapy.
Long Term IV Antibiotics
e.g. Joint infections, Endocarditis.
A District Nurse can administer once daily IV antibiotics e.g. ceftriaxone. If administration is more
frequent than this, the patient/parent is required to self-administer, or have a continuous infusion
pump (we use elastomeric pumps within the Waikato DHB). A central venous catheter line or PICC
line is usually required.
Only certain antibiotics are fully subsidised for patients in the community. Check with Pharmacy
Department to see whether it will be necessary to make an application for funding through Hospital
Exceptional Circumstances (HEC). Applications forms for HEC funding are available from
Pharmacy.
The WDHB IV Manual, Section A10, has a pre-discharge checklist and skills mastery list, essential
for all IV discharges.
Short Term IV Therapy
e.g. Completion of antibiotic course for meningitis (up to 7 days).
As above, but a peripheral line is adequate.
Chronic/Speciality Patients Requiring IV Therapy
e.g. Cystic Fibrosis, Haematology patients.
126
Contact the ward Clinical Nurse Leader or Clinical Nurse Educator – specialist areas will have
relevant protocols for chronic patients.
Community Cellulitis Protocol
This is for short-term antibiotics (three days) in the community via a peripheral line for simple
cellulitis. This protocol is used by Waikato and T Hospital Emergency Departments and is now
available to all GPs in the region.
127
LOCAL RESISTANCE PATTERNS TO ANTIMICROBIAL
DRUGS
Antimicrobial therapy is usually commenced before the causative organism is known with certainty.
The choice of agent for this “empiric therapy” depends on knowing the likely organisms and their
likely susceptibility. The Treatment Guidelines for Common Conditions section of this handbook
includes notes on the anticipated etiologic organisms. Frequently, the organism is identified in the
laboratory before susceptibility test results are available.
Most organisms are reasonably
predictable in their antimicrobial susceptibility and frequently the antibiotic spectrum used can be
narrowed once their identity is known. Susceptibility results for the individual patient’s organism
often allow it to be narrowed further.
Definitions:
•
“Susceptible” means that recommended doses of the antibiotic should be effective in commonly
encountered conditions. Many other factors can influence therapeutic success, e.g. site of
infection, presence of prosthetic material or immunosuppression.
•
“Resistant” means that an alternative agent should be considered.
•
“Intermediate” or “reduced susceptibility” means that in favourable circumstances, the antibiotic
may be effective. Increased doses may be required.
Common Organisms in Sepsis
The following data is presented as a guide to the most common organisms expected in severe
sepsis. These organisms are grouped according to their predictable susceptibility patterns.
128
Gram-Positive Bacteria
Staphylococcus aureus
Flucloxacillin remains the drug of choice. About 10% are MRSA. Check the hospital alerts system
and previous lab results because many cases of MRSA infection in previously recognised carriers.
Coagulase-Negative Staphylococci
These are frequently contaminants and don’t require treatment.
Streptococcus pneumoniae
These respond well to high dose penicillin or cephalosporins. Invasive isolates are almost always
susceptible but low level resistance is not uncommon in respiratory tract isolates
Beta Haemolytic Streptococci (Group A B C G and S. anginosus)
These are uniformly susceptible to penicillin.
Viridans Streptococci
These are also uniformly susceptible to penicillin. If MIC >0.1 µg/ml in endocarditis, gentamicin may
be required in addition. Most blood culture isolates occur in the context of mucosal barrier injury or
polymicrobial abscesses.
Enterococci
129
These are intrinsically more resistant than streptococci. A penicillin is the agent of choice. They are
intrinsically resistant to cephalosporins, cotrimoxazole and erythromycin. There has not been any
evidence of vancomycin resistance in the Waikato for nearly a decade. Vancomycin is often the
only alternative. For urinary tract infections, nitrofurantoin is often satisfactory.
Gram-Negative Bacteria
Coliforms (E. coli, Klebsiella, Proteus, Enterobacter, Serratia)
These are mostly reasonably susceptible to antibiotics, with two exceptions:
1. ESBL producing (cephalosporin resistant) E. coli and Klebsiella pneumoniae, which are
typically also multi resistant to gentamicin, cotrimoxazole and ciprofloxacin. Use of any of
these agents allows ESBL strains to spread to new patients. Oral options are few
(Fosfomycin may be of use for urinary tract infections due to ESBLs and is available with
Infectious Diseases input), but amikacin, ertapenem and meropenem are usually active.
2. Potential AmpC producing species (Enterobacter, Serratia, Citrobacter, Providencia,
Morgaella). Although initially testing susceptible in the lab, these can develop resistance to
cephalosporins after 3 or 4 days treatment so an early change to another agent is
recommended once the species is known.
Pseudomonas species
Severe sepsis may be treated with dual antibiotics, including an aminoglycoside, antipseudomonal
penicillin or cephalosporin or a fluoroquinolone.
Acinetobacters
A rare cause of sepsis.
antibiotics.
Isolates from the Waikato are usually susceptible to several standard
Stenotrophomonas maltophilia
Low pathogenicity, sometimes associated with central line infection, highly multiresistant. They are
usually susceptible to cotrimoxazole.
Neisseria meningitidis
Uniformly susceptible to ceftriaxone and all penicillins.
Haemophilus influenzae
H. influenza serotype B invasive disease has virtually been eradicated by vaccination. All our
isolates are “non typeable” and susceptible to amox-clav and cephalosporins but a few show low
level resistance of uncertain clinical significance.
Anaerobic Bacteria (Bacteroides, Clostridia, Propionibacteria and many others)
Usually present as part of a polymicrobial infection. Full identification to species level and
susceptibility testing are technically difficult and taken 1-2 weeks, so not usually performed. Most
clinical isolates of all species in NZ are susceptible to amox-clav and to meropenem. Gram negative
anaerobes (Bacteroides, fusobacterium) are almost all covered by metronidazole and gram positives
(Clostridia) by clindamycin. It is not usually necessary to cover all anaerobes; treatment of coliforms
and streptococci is the priority. A few life threatening pure anaerobic infections (eg Lemierres
disease, tetanus) require infectious disease consultation.
Yeast
Candida albicans and Candida parapsilosis
Predictably susceptible to fluconazole.
130
Other Candida species are often resistant to fluconazole e.g. C. glabrata and C. krusei.
131
Antimicrobial Susceptibility of Common Blood Culture Isolates
Waikato Hospital 2013
Recommended antibiotics for E. coli bacteraemia in order of preference:
Ceftriaxone
Gentamicin
Ciprofloxacin (If above drugs contraindicated or resistant)
Ertapenem (If multidrug resistant eg ESBL)
Recommended antibiotics for E. coli infection at other sites:
Cotrimoxazole
Amoxycillin or amox-clav
Nitrofurantoin (urine only)
Ciprofloxacin (If above drugs contraindicated or resistant)
132
Recommended antibiotics for S. aureus in order of preference:
Flucloxacillin
Cotrimoxazole (if oral therapy is appropriate)
Vancomycin (if MRSA and resistant to cotrimoxazole)
Erythromycin or clindamycin (for non life threatening conditions)
Amox-clav (if broader spectrum cover is required)
Cephalosporins (If past adverse reaction to penicillins but cephalosporins have been tolerated)
Note: mupirocin is only used for clearing nasal carriage.
Note: Coagulase negative staphylococci are normal skin flora and of low pathogenicity. Most isolates
from blood culture are contaminants. A diagnosis of true infection (eg CVL or prosthetic joint)
requires two or three positive specimens from a sterile site.
Note: Only 30 isolates of P. aeruginosa were found in blood cultures over 12 months. Isolates from
urine, sputum and wounds tend to be more resistant but are often colonisers or contaminants.
133
Resistance to any antibiotic can develop after prolonged treatment.
Report prepared by:
Dr Chris Mansell
Microbiology department
134
Infection incidence summary report 2013
(MRSA, ESBL, Clostridium difficile, VRE & MDRO)
Methicillin Resistant Staphylococcus Aureus (MRSA)
(For MRSA Incidence Graph see Appendix 1)
There were 755 cases of MRSA reported to Infection Control during 2013. This is an increase of 61
cases from 2012, and an on-going upward trend for a number of years. Cases include Hospital
acquired (HA) , community acquired (CA) MRSA and those reported to us by the community
laboratories. Pathlab results accounted for 54% of notifications (409 cases), approximately the same
percentage as 2012.
56 cases (7%) were identified as nosocomial to Waikato DHB services and 36 cases (5%) were
categorised as ‘possible’. Nosocomial cases were identified in practically all wards including the
rural hospitals. The majority of identified cases were community acquired at 651 (86%), while those
which were unable to be determined as either HA or CA, were grouped in the unknown category
with 12 cases (2%). These are the same approximate percentages as 2012.
Positive specimens came from a range of sources including screening swabs, wounds, urine, blood
cultures, sputum, tissue and aspirates. The reason specimens were collected was unknown in 53%
of isolates, this is due to the notification from Pathlab and the limited information provided. Clinical
signs and symptoms (37%) were the next most common reason for collection, with screening only
accounting for 8% of isolates identified.
The AK3 strain was the commonly identified this year at 20% of all isolates, with WSPP1 and
EMRSA-15 being the next most common at 7% each. This is an increase from last year for AK3 by
2% and a decrease for both WSPP1 & EMRSA-15 from 13% and 8% respectively.
Currently Waikato DHB chooses to send all their multi resistant isolates to ESR for typing whereas
Pathlab and other DHB’s do not, therefore 54% of our strains were classified as ‘not sent’ or
‘unknown’.
There was an almost even split in results for male (49%) and female (51%), and patients ranged in
age from less than 1 to 98 years old.
Extend Spectrum Beta Lactamase (ESBL)
(For ESBL Incidence Graph see Appendix 2)
There were 286 new patients identified with ESBL isolates in 2013. Organisms identified included E.
coli, E. cloacae, Klebsiella pneumonia, Klebsiella oxytoca and Proteus mirabilis.
Isolate specimens included blood cultures, urine, faeces, sputum, wound swabs, rectal swabs, and
tissue samples. Urine was the most common specimen (73%) that ESBL was identified from, with
rectal screening swabs accounting for 18% of ESBL’s identified.
These isolates were identified to us are from within Waikato DHB facilities (including rural hospitals),
from the community (Pathlab) and from other District Health Boards. Just over half of the isolates
were identified at Pathlab (53%).
81% of isolates were defined as community acquired, 12% as hospital acquired, and 6% possibly
hospital acquired. The remaining 1% was not able to be identified in any of the above classifications,
so were grouped into the unknown category. Hospital acquired increased 3% from 2012; this may
be attributable to the start of the ESBL outbreak at Rhoda Read Continuing Care facility in
December 2013.
18% of specimens were collected for screening purposes, which tie in with 18% of ESBL’s being
identified from rectal screening swabs. 41% of specimens were taken for clinical signs and
135
symptoms, and 41% were unknown, these are commonly the Pathlab results where no clinical
information is available. These are very similar to last year’s specimens. Patients ranged in age from
less than 1 to 95 years old, with 72% (142) being female, an increase of 3% from 2012. All isolates
in 2013 were multi-resistant.
Clostridium difficile associated diarrhoea (CDAD)
(For Clostridium difficile Incidence Graph see Appendix 3)
From 1st January 2013 to 31st December 2013, data was collected on 84 patients with faeces
positive for C. difficile. These figures include patient samples and tests undertaken for outside
agencies.
The definition used to define nosocomial infection is;
1. Hospital-Acquired (HA): patient with CDAD symptom onset more than 24 hours after
admission to Health Care Facility (HCF).
2. Community onset-HCF associated (CO-HCFA): patient with CDAD symptom onset in the
community or 48 hours or less after admission to a HCF, provided that symptom onset was
less than 4 weeks after the last discharge from a HCF.
3. Community-acquired (CA): patient with symptom onset in the community or 48 hours or less
after admission to any HCF providing symptom onset was more than 12 weeks after the last
discharge form a HCF.
4. Indeterminate disease: patient who does not fit any of the above criteria for an exposure
setting e.g. patient who has symptom onset in the community buy: patient who does not fit
any of the above criteria for an exposure setting e.g. patient who has symptom onset in the
community but who has discharged from the same or other HCF 4-12 weeks before
symptom onset.
The 84 cases is a decrease from 131 cases in 2012. Of the 84 cases with CDAD, 41 (49%) were
defined as hospital-acquired, 17 (20%) CO-HCFA, 6 (7%) were of indeterminate disease, and 20
(23%) community-acquired. The incidence of hospital-acquired and community acquired cases
decreased from 2012, while the number of CO-HFCA and indeterminate cases increased.
The highest numbers of cases were identified in the fourth quarter with increase being in community
acquired cases.
The age of patients with CDAD ranged from 20 to 98 years of age, with a mean age was 67 years
for all CDAD. Infants under the age of 2 years were excluded from the surveillance.
Patients with CDAD were identified in 25 clinical areas across Waikato DHB. Ward M5 had the
highest number of patients identified with CDAD in their area, with the majority being CO-HCFA,
while Ward M3 had the highest incidence of hospital-acquired infections.
The two major risk factors for development of CDAD are exposure to the organism and exposure to
antibiotics, particularly third generation cephalosporins. Other risk factors include altered bowel
function e.g. following bowel surgery and/or altered nutrition. 78% of CDAD cases received
antibiotics which is a slight increase from 2012, while only 7% of cases had exposure to C.difficle, a
significant decrease from 24% in 2012.
25% of CDAD cases experienced bowel surgery / bowel infection or impaired nutrition, the same as
last year, and no cases required bowel surgery as a result of C.difficle infection complications.
Vancomycin Resistant Enterococci (VRE)
There were two cases of VRE identified in 2013, both were E.faecium species, and identified from a
faecal sample and rectal screening swab.
Both cases had been overseas prior to admission. The first case was a 27 year old female who
presented with diarrhoea & vomiting two days after surgery at Braemar Hospital, having returned
from holidaying in Bali 10 days prior.
The second case was an 88 year old male who was transferred to Waikato Hospital directly from an
Australian hospital, following an admission and surgery for a fractured neck of femur.
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Multi Drug Resistant Organism (MDRO)
There was one case of a multi-drug resistant organism reported in 2013, the organism a
Pseudomonas aeruginosa was identified from aortic graft tissue following the patient suffering from
recurrent pseudomonas bacteraemia’s throughout 2012.
Compiled by Lisa Maxwell (CNS) on behalf of Infection Prevention & Control Team
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Appendix 1: MRSA Incidence Graph
Waikato DHB MRSA Incidence
Colonised and clinical infections
800
Unknown
700
NOT STATED
DISTINCT
BORSA
600
Not sent
Untypeable
500
Other Strains
AKH3
TANS 2
400
WSPP 2
WSPP 1
USA 300
300
AK3
WR/AK1
200
AkH4
EMRSA 1 5
100
0
1989 1990 1991 1992 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Appendix 2: Extended Spectrum Beta Lactamase Incidence Graph
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Appendix 3: Clostridium difficile Incidence Graph
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MRSA Management
The control of MRSA is important because the alternatives to beta-lactams are more toxic,
more expensive and less effective. New Zealand is in the fortunate position where beta
lactams can be confidently used as initial treatment in conditions where S. aureus infection is
suspected. In 2013 about 10% of S. aureus from blood cultures at Waikato Hospital were
MRSA, although this figure fluctuates depending on local outbreaks. In many parts of the
world, over 30% of S. aureus is MRSA. Patients found to be positive are isolated or
cohorted and receive appropriate treatment and follow up.
MRSA Strain Types in the Waikato 2011 to 2013
Chris Mansell and Lynne McLeod have recently undertaken a major work looking at MRSA
strains at Waikato Hospital. They have undertaken the following three analyses using 1107
MRSA cases over the last three years.
Analysis
What strains of MRSA are present in the Waikato?
What are the antibiotic sensitivity profiles of each strain?
Can the strain be deduced from the antibiotic sensitivity pattern?
As can be seen from the following tables, the predominant strains at Waikato Hospital are
AK3, EMRS15 and WSPP strains. Most of the MRSA strains encountered in the Waikato
can be treated with cotrimoxazole if oral therapy is required.
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An alternative way of looking at the antibiogram is whether the resistance profile can determine the strain type. It appears from the following figures that EMRSA-­‐15 is relatively distinct based on Ciprofloxacin resistance and erythromycin susceptibility. However AkH4 is not as predictable based on the antibiogram. 144
AK3 can be recognised reasonably well when resistance to fusidic acid and
susceptibility to mupirocin is present.
The management of MRSA outbreaks is directed by the Infection Control Team and
may vary for each particular outbreak. The location, type of clinical service, staffing
and strain of MRSA will influence strategies for isolation, screening and decolonisation.
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BLOOD AND BODY FLUID EXPOSURES
Needlestick injuries and mucous membrane splashes are the most common
recognised incidents where healthcare workers may be exposed to infectious diseases.
Pathogens of major concern include Hepatitis B, Hepatitis C and HIV.
In some circumstances, prophylaxis or monitoring may be indicated after exposure to
Neisseria meningitidis, Hepatitis A virus, bites, sexual assault, Tuberculosis, Varicella
(non-immune pregnant or immunosuppressed people), Haemophilus influenzae type B,
Influenza, Rabies, biological weapons. These cases should be discussed with an
appropriate specialist.
Procedures for dealing with Needlestick and Mucous Membrane
Exposures
Similar procedures should be used for dealing with needlestick injuries and mucous
membrane exposures, although risk of infection following mucous membrane exposure
is much lower. Blood contact with intact skin is not a risk exposure. A “Body Fluid
Exposure Pack” is available to guide management. Packs are available at Health and
Safety, Emergency Department, Delivery Suite and Theatre
First Aid Measures
•
•
•
•
•
•
Wash and gently encourage bleeding. Attend to injuries.
Document identity of source and exposed people.
Arrange for a doctor, Health and Safety advisor or other trained person (e.g.
Clinical Nurse Leader) to manage the incident, arranging collection of specimens,
checking results and ensuring follow-up. In general, people should not manage
their own exposure incident. The incident form included within the “Exposure
Pack” needs to be completed and sent to health and safety to ensure
process is complete and appropriate follow-up put in place.
Routinely obtain blood (request form included in “Exposure Pack”) from both
source and exposed people and test both for:
- HBsAg
- Anti-HBs
- Anti-HBc
- Anti-HCV
- HIV antigen and antibody
Assess risk status of source person. Are they likely to be early in acute infection
with one of the 3 viruses or is blood not available for testing?
Clarify Hepatitis B immunisation status of the exposed person. Health and Safety
will help with this on receipt of the incident form.
Management of Documented Exposures
HBV
•
•
•
Risk of infection for a non-immune exposed person is 5-30%, depending on the
HBeAg status of the source.
HBV immunoglobulin is given within 72 hrs if exposed person is non-immune.
HBV vaccination is commenced.
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HCV
•
•
•
Risk of infection is approximately 3%.
Exposed person is monitored for development of Hepatitis C, particularly
asymptomatic infection.
If infection occurs, treatment of acute Hepatitis C may be initiated.
HIV
•
•
•
•
•
•
Risk of infection is approximately 0.3%, but considerably less if the source is
having effective antiretroviral treatment and has an undetectable HIV viral load.
HIV infection is now a manageable chronic condition with excellent life expectancy
and quality of life for those diagnosed and under care.
Prophylaxis should generally not be given unless a definite exposure has occurred.
Antiretroviral prophylaxis have side effects and the risk/benefit analysis needs to
be undertaken
The ideal time frame for administration is thought to be within 2 hours, but
sometimes longer delays are unavoidable.
Only a “specialist experienced in the treatment of patients with HIV as approved
and named by the Ministry of Health” may prescribe antiretroviral prophylaxis.
The people to contact (through Waikato Hospital telephonist) are, in order:
- Dr Graham Mills or Dr Paul Huggan, Infectious Disease Physicians.
- Dr Jane Morgan, Sexual Health Physician.
- Auckland Hospital Infectious Disease Service (available 24hr).
Please persist in making contact with one person on this list if source blood
is HIV positive to assess need for urgent commencement of antiretroviral
therapy. A starter pack is available within the Waikato Hospital emergency
department.
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NOTIFIABLE DISEASES IN NEW ZEALAND
Notifiable Infectious Diseases Under The Health Act 1956
And Tuberculosis Act 1948
Infectious Diseases Notifiable to a Medical Officer of Health and Local
Authority (Public Health staff will notify the Local Authority where
required).
Acute gastroenteritis*
Campylobacteriosis
Cholera
Cryptosporidiosis
Giardiasis
Hepatitis A
Legionellosis
Listeriosis
Meningoencephalitis = primary amoebic
Salmonellosis
Shigellosis
Typhoid and paratyphoid fever
Yersiniosis
* Not every case of acute gastroenteritis is necessarily notifiable - only those where
there is a suspected common source or from a person in a high risk category, (e.g.
food handler, child care worker, etc.) or single cases of chemical, bacterial, or toxic
food poisoning such as botulism, toxic shellfish poisoning (any type) and disease
caused by verocytotoxic E. coli.
Infectious Diseases Notifiable to Medical Officer of Health
Acquired Immunodeficiency Syndrome
Arboviral diseases
Creutzfeldt Jakob Disease and other
Spongiform encephalopathies
Haemophilus Influenzae B
Hepatitis C
Hydatid disease
Leptospirosis
Measles
Neisseria meningitidis invasive disease
Plague
Rabies
Rickettsial diseases
Severe Acute Respiratory Syndrome (SARS)
Tetanus
Anthrax
Brucellosis
Diphtheria
Hepatitis B
Hepatitis (viral) - not otherwise specified
Leprosy
Malaria
Mumps
Pertussis
Poliomyelitis
Rheumatic fever
Rubella
Tuberculosis (all forms)
Viral haemorrhagic fevers
Yellow fever
Diseases Notifiable to Medical Officer of Health
(Other than Notifiable Infectious Diseases)
Cysticercosis
Lead absorption equal to or in excess of
Taeniasis
15µg/dL (0.72µmol/L) **
Trichinosis
Poisoning arising from chemical
Decompression sickness
contamination of the environment
**Blood lead levels to be reported to the Medical Officer of Health (15µg/dL or
0.72µmol/L) are for environmental exposure. Where occupational exposure is
suspected, please notify OSH through the NODS network.
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How To Notify A Notifiable Disease
(Include Suspected Cases)
During times of increased incidence practitioners may be requested to report with
informed consent, to their local Medical Officer of Health cases of communicable
diseases not on this list.
Notification by phone is preferred, since the Ministry of Health notification forms have
too little information.
Contact Phone Numbers:
Normal Office Hours (0800 - 1700)
Waikato Hospital
ext 22065 or 22020
Hamilton region
(07) 8581065
Outside Hamilton region
0800 800 977
For specific advice, ring phone numbers above or contact
On Call Medical Officer of Health
021 359 650
Dr Antia Bell
021 473 854
Dr Felicity Dumble
021 359 646
Dr Richard Wall
021 831 137
Facsimile for Public Health
07 838 2382
After Hours and Weekends
Phone Waikato Hospital operators and ask for the Medical Officer of Health on-call or
phone 021 359650.
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