In the Clinic: Evidence Based Management of Infections Daniel Deck, Pharm.D. San Francisco General Hospital Overview  Community-acquired pneumonia  Upper respiratory tract infections  Urinary tract infections  Skin and Soft-tissue infections Community-acquired pneumonia Community Acquired Pneumonia (CAP): definition    At least 2 new symptoms Fever or hypothermia Cough Rigors and/or diaphoresis Chest pain Sputum production or color change Dyspnea New infiltrate on chest x-ray and/or abnormal chest exam No hospitalization or other nursing facility prior to symptom onset Diagnosis  Chest radiograph – needed in all cases?  Avoid over-treatment with antibiotics  Differentiate from other conditions  Specific etiology, e.g. tuberculosis  Co-existing conditions, such as lung mass or pleural effusion  Evaluate severity, e.g. multilobar  Unfortunately, chest physical exam not sensitive or specific and significant variation between observers Arch Intern Med 1999;159:1082-7 Microbiological Investigation  Sputum Gram stain and culture  Remains somewhat controversial  30-40% patients cannot produce adequate sample  Most helpful if single organism in large numbers  Usually unnecessary in outpatients  Culture (if adequate specimen < 10 squamous cells/LPF; > 25 PMNs/LPF): antibiotic sensitivities  Limited utility after antibiotics for most common organisms Etiology  Clinical syndrome and CXR not reliably predictive  Streptococcus pneumoniae 20-60%  Haemophilus influenzae 3-10%  Mycoplasma pneumoniae up to 10%  Chlamydophila pneumoniae up to 10%  Legionella up to 10%  Enteric Gram negative rods up to 10%  Staphylococcus aureus up to 10%  Viruses up to 10%  No etiologic agent 20-70% “Atypicals” S. pneumoniae  2/3 of CAP cases where etiology known  2/3 lethal pneumonia  2/3 bacteremic pneumonia  Apx. 20% of cases with pneumococcal pneumonia are bacteremic (variable)  Risk factors include Extremes of age Alcoholism COPD and/or smoking Nursing home residence Influenza Injection drug use Airway obstruction *HIV infection S. pneumoniae – drug resistance    ~ 25-35% penicillin non-susceptible by old standard nationwide, but most < 2 mg/mL Using the new breakpoints for patients without meningitis, 93% would be considered susceptible to IV penicillin Other beta-lactams are more active than pencillin, especially Ceftriaxone, cefotaxime, cefepime, amoxicillin, amoxicillin-clavulanate S. pneumoniae – drug resistance  Other drug resistance more common with increasing penicillin minimum inhibitory concentration (MIC)  Macrolides and doxycycline more reliable for PCN susceptible pneumococcus, less for penicillin nonsusceptible   Trimethoprim-sulfamethoxazole not reliable Fluoroquinolones – most S. pneumoniae are susceptible  Clinical failures have been reported  No resistance with vancomycin, linezolid Risk Factors for Drug-Resistant Pneumococcal Pneumonia  Age < 2 year or > 65 years  -lactam antibiotics within 3 months  Alcoholism  Immunocompromised patients  Multiple comorbidities  Exposure to children in day care centers Conditions that Increase the Morbidity/Mortality of CAP  COPD  CHF  Alcoholism  CAD  Leukopenia  Malignancy  Bacteremia  Neurologic disease  Diabetes mellitus  Chronic liver disease  Renal insufficiency  Immunosuppression IDSA Outpatient Empiric Therapy Recommendations Previously Healthy & NO DRSP Risk Factors DRSP Risk Factors or High Level Macrolide Resistance > 25% Macrolide (e.g azithromycin) or Doxycycline 1) Fluoroquinolone* or 2) a β-Lactam# plus a Macrolide or Doxycycline *moxifloxacin, gemifloxacin, or levofloxacin (750mg) 1 gm PO tid or Augmentin® XR 2 gm PO bid are preferred. Ceftriaxone, cefpodoxime proxetil, and cefuroxime axetil 500 mg PO bid are alternatives #Amoxicillin We love doxycycline   Adult inpatients June 2005 – December 2010 Compared those who received ceftriaxone + doxycycline to those who received ceftriaxone alone  2734 hospitalizations: 1668 no doxy, 1066 with doxy  Outcome: CDI within 30 days of doxycycline receipt  CDI incidence 8.11 / 10,000 patient days in those receiving ceftriaxone alone; 1.67 / 10,000 patient days in those who received ceftriaxone and doxycycline Doernberg et al, Clin Infect Dis 2012;55:615-20 Duration of Therapy    5 days should be the minimum duration of therapy Patients should be afebrile for 48-72 hours No more than 1 CAP-associate sign of clinical instability (T > 37.8ºC, HR >100, RR > 24, SBP < 90, O2 sat < 90%, pO2 < 60) Short-Course Therapy     Defined as less than 7 days of therapy Short course therapy may reduce side effects, cost, and resistance Azithromycin has been used for 3-5 days Ceftriaxone, amoxicillin, and fluoroquinolones have been used for 5 days Reasons for Inadequate Response to Empiric Therapy  Inadequate Antibiotic Selection  Unusual Pathogens  Complications of Pneumonia  Incorrect Diagnosis  Drug-resistant organisms Upper Respiratory Tract Infections Upper respiratory tract infections  Rhinosinusitis ~13 million outpatient visits per year Viral causes >>>> bacterial Minimal to NO benefit from antibiotics given for short duration of disease Xray/CT not helpful in distinguishing cause Rhinosinusitis diagnosis Major Criteria Minor Criteria  Purulent anterior nasal discharge  Headache  Purulent posterior nasal discharge  Ear pain, pressure, or fullness  Nasal congestion or obstruction  Halitosis  Facial congestion or fullness  Dental pain  Facial pain or pressure  Cough  Hyposomia or anosmia  Fever (chronic disease)  Fever (acute disease)  Fatigue Need at least 2 major or 1 major and ≥ 2 minor criteria IDSA guidelines: rhinosinusitis  Antibiotics may be helpful if…. 1. Persistent signs/symptoms > 10 days 2. Severe symptoms  Fever > 39C  Purulent nasal drainage for 3 consecutive days  Facial pain 3. Biphasic illness IDSA guidelines: rhinosinusitis Recommened st line therapy =  1 Amoxicillin/clavulante (standard dose)  Consider high dose (XR formulation) with severe disease, elderly, recent antibiotic use or hospitalization   Alternatives: doxycycline, levofloxacin Treatment duration: 5-7 days Not Recommended • Macrolides • TMP/SMX • Oral cephalosporins • Routine MRSA coverage IDSA guidelines: rhinosinusitis DO  Antibiotic duration 5-7 days DO NOT  Decongestants  Nasal saline irrigation  Antihistamines  Intranasal corticosteroids  NP swab  Consider changing abx if  Clinically worse at 48-72 hours  No improvement at 3-5 days GAS pharyngitis  Accounts for 15% of adult sore throat visits  Dx: culture or rapid antigen test  Tx : 1st line = PCN or amoxicillin x 10 days Mild PCN allergy = cephalexin x 10 days Alternatives = clindamycin or clarithromycin x 10 days OR azithromycin x 5 days Antibiotic allergies: History is key! Past reaction  Source Current reaction  Timeline: symptoms & meds  Timeline: symptoms & meds  Labs, histology  Detailed description  Concurrent illness  Treatment  Concurrent illness  Workup  Other exposure Algorithm for the use of cephalosporins in patients with reported penicillin allergy Practical management of antibiotic allergy in adults. McLean-Tooke et al, J Clin Pathol 2011;64:192-199 Acute bronchitis  10 million healthcare visits annually  80% of patient prescribed antibiotics  95% of case have a viral etiology  Antibiotics = No clinical benefit plus increased cost, adverse reactions, increased antibiotics resistance Skin and Soft Tissue Infections Skin Infection Anatomy Epidermis Impetigo Erysipelas Dermis Subcut. Fat Fascia Muscle Cellulitis Abscess, furuncle, carbuncle Fasciitis Pyomyositis S. pyogenes Resistance in the U.S. 2002-2003 Antimicrobial Agent Percent Resistant* Penicillin 0.0% Cefdinir 0.0% Clindamycin 0.5% Erythromycin 6.8% Azithromycin 6.9% Clarithromycin 6.6% Levofloxacin *Richter SS. Clinical Infectious Diseases 2005; 41:599–608 0.05% S. aureus Susceptibilities from Outpatient Wound Isolates Antimicrobial Agent Percent Susceptible* Oxacillin 52.0% Trimethoprim-Sulfamethoxazole 99.6% Clindamycin 86.7% Erythromycin 41.5% Tetracycline 93.8% Vancomycin 100% *http://ww2.cdph.ca.gov/PROGRAMS/MDL/Pages/CaliforniaAntibiogramProject.aspx Risk Factors for CA-MRSA  Prior history of MRSA infection  Close contact with person with similar infection  Recent antibiotic use  Reported “spider bite”  Outbreaks in IVDU, prisoners, athletes, children, Native Americans Cellulitis vs Abscess Cellulitis Abscess Pathogen Beta-hemolytic streptococci Staph aureus (CA-MRSA) Treatment Antibiotics Incision and Drainage +/- ABX Antibiotics Duration • • • • Penicillin (amoxicillin) Cephalosporins (cephalexin) Clindamycin (PCN allergic) TMP/SMX??? 5-10 days; monitor clinical response • • • • TMP/SMX Doxycycline Clindamycin Linezolid $$$ Abscess: when to prescribe abx?  Antibiotics may be warranted if  Abscess is large (> 5 cm) or incompletely drained  Significant surrounding cellulitis  Systemic signs and symptoms of infection are present  Patient is immunocompromised  Difficult to drain area (face, hand, genitalia)  Extremes of age Animal & Human Bite Wounds  One half of all Americans bitten in their lifetime  80% of wounds are minor, 20% require medical care   Human and cat bites frequently become infected so always require treatment even if not grossly infected Only 5% of dog bites get infected so treatment indicated if bite is severe, grossly infected, or significant comorbidity (e.g. diabetes) Bite Wound Treatment   Wound cleaning, irrigation and debridement! Antibiotics directed against skin flora of patient and oral flora of biting animal/human  Humans (viridans strep, Eikenella, mixed anaerobes)  Dogs (Pasteurella, Capnocytophaga, anaerobes)  Cats (Pasteurella, anaerobes)  Antibiotic Regimens  Oral Urinary Tract Infections Increasing resistance in urinary pathogens     E.coli accounts for ~95% of all cases TMP/SMX resistance in E.coli > 20% in many parts of the United States Resultant shift to use of quinolones as first-line empirical therapy over the past 10-20 years Quinolones have been associated with “collateral damage”  Increased rates of MRSA  Selection for resistant GNRs including ESBL- producers  Clostridium difficile-associated diarrhea When to get a culture?  Suspect multidrug-resistant organism  Recent abx  Prior infection or colonization  Recent travel   Suspect pyelonephritis Follow up cultures unnecessary in patients whose symptoms resolve 2010 IDSA recommended treatment regimens for uncomplicated cystitis First Line Regimens    Nitrofurantoin macrocrystals (Macrobid®) 100 mg BID X 5 days (avoid if early pyelo suspected) Trimethoprim-sulfamethoxazole 1DS tablet BID X3 days (avoid if resistance prevalence exceeds 20% or if used for a UTI in previous 3 months) Fosfomycin trometamol 3 grams x 1 dose (lower efficacy than some other agents, avoid if early pyelo suspected) Gupta K et al. Clin Infect Dis. 2011;52(5):103-20. Second Line Regimens   Ciprofloxacin 500 mg BID x 3 days (resistance prevalence high in some areas) Oral β-lactams (including amoxicillin/clavulante, cefdinir, cefaclor, cefpodoxime, cephalexin (less data); avoid ampicillin or amoxicillin alone; lower efficacy than other available agents, treat for 3 to 7 days) What is fosfomycin?    Phosphonic acid derivative that inhibits cell wall synthesis Activity against many gram positive and gram negative organisms In U.S., only oral salt available as a powder sachet dissolved in water  High concentration in the urine  Usual dose 3g x 1 (single dose)  Can also consider 3g every other day x 3 doses or 3g q 72 hrs. x 14 days  3g packet costs about $50 Treatment of cystitis: Back to the future Nitrofurantoin (Macrobid®) PROS Fosfomycin trometamol PROS  As effective as TMP/SMX  Clinical efficacy similar to TMP/SMX  Minimal drug resistance  Low propensity for collateral damage  Low propensity for collateral damage  Single dose therapy CONS     Blood levels not sufficient to treat early pyelonephritis Avoid in pts with CrCl < 50 ml/min Nausea, headache (similar adverse effect rate as TMP/SMX) Rare pulmonary hypersensitivity CONS     Microbiologic efficacy lower than TMP/SMX and nitrofurantoin Not sufficient to treat early pyelo Susceptibility testing not routinely performed Diarrhea, nausea, headache (similar adverse effect rate as nitrofurantoin) Other oral options for cystitis due to resistant organisms   Amoxicillin-clavulanate (susceptible ESBL-producing E. coli) Nitrofurantoin Fosfomycin references:  Falagas et al, Lancet Infect Dis 2010;10:43-50  Neuner et al, Antmicro Agents Chemother 2012;56:5744-48 Asymptomatic Bacteriuria  Do not screen if no symptoms are present  Except in pregnancy  Other special situations  Do not prescribe antibiotics!  Relative Risk ~3x for recurrence of symptomatic bacteriuria when asymptomatic patients receive antibiotics Final Questions?  Contact Info  Extension: 415-206-5574  Email: [email protected] SFGH “As real as it gets”