GUIDE TO ANTIMICROBIAL THERAPY FOR ADULTS
GUIDE TO ANTIMICROBIAL THERAPY FOR ADULTS FLETCHER ALLEN HEALTH CARE 10th Edition 2006-2007 PREPARED BY: THE INFECTIOUS DISEASE PRACTICE COMMITTEE Christopher Grace, MD, Co-Chairman (Infectious Disease) John Ahern, PharmD, BCPS Co-Chairman & Editor (Pharmacotherapy) Kemper Alston, MD (Infectious Disease) Elizabeth Bonney (Obstetrics & Gynecology) David Clauss, MD (Emergency) Thomas Connolly, DMD (Surgery) Maj Eisinger, MD (Emergency) Steve Grant (Internal Medicine) Beth Kirkpatrick, MD (Infectious Disease) Karen McBride (Pharmacotherapy) Christine Northrup, MD (Internal Medicine) Tom Peterson, MD (Family Practice) Mary Ramundo, MD (Infectious Disease) Michael Young, MD (Intensive Care) Washington Winn, MD (Microbiology) Approved by : The Executive Committee The Pharmacy and Therapeutics Committee Copyright Fletcher Allen Health Care, Inc. 1996 1 TABLE OF CONTENTS Introduction ............................................................................................................. 4 Balance the Risk ..................................................................................................... 5-6 Common Sense Guidelines to Infectious Disease Management............................ 7 Description of the Antimicrobial Management Program at FAHC ........................... 8 Antimicrobial Drugs on the FAHC Formulary .......................................................... 9 FAHC Microbiology Susceptibility Chart ................................................................. 10 Aminoglycoside Antibiotics ..................................................................................... 11-15 • General Principles .................................................................................. 11 • Once Daily Dosing .................................................................................. 12-13 • Traditional Dosing................................................................................... 14-15 Vancomycin ............................................................................................................ 16-17 • Criteria for Use........................................................................................ 16 • Dosing and Monitoring............................................................................ 17 Guidelines for Criteria-Based Antibiotics ................................................................ 18-22 • • • • • • Ampicillin / sulbactam ............................................................................. 19 Azithromycin ........................................................................................... 20 Cefotetan ................................................................................................ 20 Ceftriaxone ............................................................................................. 21 Levofloxacin............................................................................................ 22 Norfloxacin.............................................................................................. 22 Guidelines for Selected Controlled Antibiotics ........................................................ 23-27 • • • • Ceftazidime............................................................................................. 24 Ciprofloxacin ........................................................................................... 25 Piperacillin / tazobactam......................................................................... 26 Meropenem............................................................................................. 27 Guidelines for Specific Infections............................................................................ 28-61 • • • • • • • • • • • Community and Nosocomial / Nursing Home Acquired Pneumonia....... 29-32 Intra-abdominal Infections ...................................................................... 33-37 Urinary Tract Infections........................................................................... 38-39 Diabetic Foot Infections .......................................................................... 40-41 Fever and Neutropenia ........................................................................... 42-43 Female Upper Genital Tract Infections ................................................... 44-45 Bite Wound Infections............................................................................. 46-47 Infectious Diarrhea & C. difficile.............................................................. 48-52 Principles of Surgical Prophylaxis........................................................... 53-55 Prevention of Bacterial Endocarditis....................................................... 56-58 Therapy for Selected Sexually Transmitted Diseases ............................ 59-60 2 • Post-Exposure Prophylaxis..................................................................... 61 3 Oral Antimicrobial Therapy.......................................................................... 62-69 • • • • • • • • • • Introduction ............................................................................................. 63 Selected Oral Agents.............................................................................. 64-66 -Amoxicillin/clavulanate .................................................................. 64 -Azithromycin .................................................................................. 64 -Cefpodoxime ................................................................................. 65 -Ciprofloxacin.................................................................................. 65 -Levofloxacin................................................................................... 66 -TMP/SMX ...................................................................................... 66 IV to PO Switch Table............................................................................. 67 Costs to Patients..................................................................................... 68-69 Antibiotic Prescribing .............................................................................................. 70-75 • Renal Dosing Table ................................................................................ 71 • Important Antimicrobial Drug Interactions............................................... 72-73 • Antimicrobials in pregnancy.................................................................... 74-75 DISCLAIMER This handbook is provided solely as a general guide. The information contained in this handbook is presented in summary form and does not constitute medical advice. As medical advice must be tailored to the specific circumstances of each individual patient, and because medical knowledge changes rapidly, nothing provided in this handbook should be used as a substitute for medical advice or the judgement of the responsible clinician. Readers are encouraged to consult numerous sources in determining the appropriate patient treatment. The authors have used sources believed to be reliable in compiling the information contained in this handbook. However, neither the authors, Fletcher Allen Health Care, Inc. nor the University of Vermont make any claims, promises or guarantees about the accuracy, completeness or adequacy of this information. They are also not responsible for any errors or omissions or for the results obtained from the use of this information. 4 INTRODUCTION The purpose of this handbook is to provide guidance to the clinician in the management of infectious diseases in adult patients. Since all patient care needs to be individualized, this handbook is not all inclusive nor is the content meant to represent a rigid approach to care. It has been written by the Infectious Disease Practice Committee, a subcommittee of the Pharmacy and Therapeutics Committee. It has been tailored specifically for Fletcher Allen Health Care. This is the fourth edition of the booklet and future editions will be expanded and updated. Please feel free to contact any member of the committee with feedback and suggestions for future editions. Through the use of this guide, it is hoped that antimicrobial agents will be used judiciously. The modern era of antibiotic therapy has seen great advances in the management of infectious diseases. However, these advances have brought two major detrimental trends: 1. INCREASING RESISTANCE TO ANTIBIOTICS: Since the development of resistance by Staphylococci to penicillin early after its introduction in the 1940’s, the overuse of antimicrobial agents has been associated with the development of resistant pathogens. The emergence of multiply resistant gram-negative and gram-positive bacteria has become a medical emergency that threatens our ability to treat and cure our patients. The overuse of any antibiotic will lead to resistance to that agent. This is especially true for the newer broad spectrum agents such as the second and third generation cephalosporins (cefotetan, ceftriaxone, ceftazidime) carbapenems (imipenem and meropenem), beta-lactamase inhibitor combinations (amoxicillin-clavulanate, ampicillinsulbactam, piperacillin-tazobactam), fluoroquinolones (ciprofloxacin, norfloxacin, levofloxacin and trovafloxacin), and glycopeptide (vancomycin) antibiotics. Multiply resistant E.coli, Klebsiella, Pseudomonas, Acinetobacter, Staphylococci and Enterococci (to name but a few) are increasing at FAHC due in large part to the overusage of antibiotics. The use of any antibiotic must be looked upon as a double edged sword. In addition to killing the bacteria infecting your patient the drug you prescribe will select for resistant bacteria. These resistant bacteria may not only infect your patient but may also be spread to other patients in the hospital, clinics, and community (esp. nursing homes). 2. INCREASING COSTS: There will continue to be intense pressure on us to control the costs of health care while maintaining the quality of care for our patients. In this age of managed care and capitated costs we must be cognizant of the expense of the antibiotics we prescribe. There are many therapeutic options available to us when treating our patients (that is, there are many ways to skin a bacterium). Efforts to use less costly though equally effective agents must be made. The newer more expensive heavily marketed agents are not necessarily better. 5 BALANCE THE RISK We are please to provide you the latest edition of the FAHC “Green Book”. This pocket book is meant to help you prescribe antibiotics judiciously and safely. With delivery of this book comes a concern and a plea. There has been an alarming increase in infections with methicillin resistant Staphylococcus aureus, (MRSA) and Clostridium difficile colitis. Both of these infections are related to the overuse of antibiotics. The relationship between increasing drug use and increasing infection is clear. These nosocomial infections result in significant patient morbidity, mortality, length of stay and costs. Our current bed availability problems are exacerbated by these infections. Antibiotic use has been shown to increase nosocomial colonization with MRSA (relative risk as high as 11.3) and C. difficile (relative risk as high as 28.6) [Safdar N and Maki DG, Ann Int Med 2002;136:834-844] It is important to BALANCE THE RISK (toxicities, superinfections, and costs) of using antibiotics against the benefit you hope to achieve. Traditionally we have leaned in the direction of more antibiotics, not less, in treating our patients. Often though, the antibiotics we depend on to cure infections are causing infections themselves. With each antibiotic prescription you write, a balance must be struck between the desired benefits of the antibiotic and the risks those antibiotics may cause. 6 In order to reduce the incidence of these infections we need to decrease our antibiotic use, especially broad-spectrum agents. The following questions should be reviewed before prescribing antibiotics: Does the patient really need the antibiotic? Does the risk of using the antibiotic out-weight the risk to your patient of contracting MRSA or C.difficile colitis? Can you narrow the spectrum of the antibiotic from the initial empiricism or once culture data is available? Can you switch to oral agents once your patient has stabilized? We encourage the use of Infectious Diseases consultation to assist you with making these important decisions. Remember to Balance the Risk 7 COMMON SENSE GUIDELINES TO INFECTIOUS DISEASE MANAGEMENT 1) Before judging the importance of a culture, consider the clinical diagnosis. Not all positivecultures need treatment and a negative culture does not exclude infection. 2) A good history and physical is far more important than “pan-culturing”. 3) Not all fevers are due to infection. Not all patients with infection have fevers. 4) Always get appropriate cultures prior to starting therapy. Culturing the patient while on antibiotics has a low yield. 5) Review the gram stain of a specimen such as sputum when attempting to determine the need to treat a positive culture. Many positive cultures represent contamination or colonization and may not need to be treated. 6) Use the most narrow spectrum agent available in treating your patient’s infection. 7) Whenever you select an antibiotic know how much it will cost. Attempt to select the less expensive though equally effective antibiotic. 8) When your patient stabilizes, consider switching to oral therapy if appropriate. 9) If the patient is failing empirical antibiotic therapy, a re-evaluation of the cause of the failure is more important than broadening or changing the empirical antibiotic regimen. 10) The antibiotic you give to your patient goes not only to the site of infection but to all the tissues of your patient. It will alter the normal (protective) skin, bowel, and oral flora of your patient. Resistant pathogens can replace the normal flora and may then cause infections. 8 ANTIMICROBIAL MANAGEMENT PROGRAM 1. Formulary System: The formulary is the group of antimicrobials available for use by FAHC staff. The formulary antimicrobials are divided into three main classes which determines how they may be prescribed: a. Open Antibiotics that are intended for routine use and have no restrictions. b. Criteria based Antibiotics that may be utilized only for the criteria as outlined on pages 19-22. Use of these agents will be monitored. Utilization of these antibiotics for situations not listed in the criteria requires approval by Infectious Disease. c. Controlled Antibiotics that require approval by Infectious Disease before they can be prescribed. These agents will not be released by the Pharmacy until they are notified by Infectious Disease to do so. Exceptions to this rule are noted on the formulary list on page 9. Please note that controlled antibiotics can be prescribed between the hours of 10 PM and 8 AM without infectious disease approval. However, infectious disease must be called in the morning for approval to continue the antibiotic. 2. Monitoring and Evaluation: Pharmacy and Infectious Disease will review use of all criteria-based and controlled antibiotics within 48-72 hours after the initial dose. Housestaff will be contacted with suggestions for change by the infectious disease pharmacist. The results of current antibiotic reviews suggest the need for improvement in the following two areas: a. Narrowing the spectrum of antibiotic therapy once culture and sensitivity results are available. b. Utilizing the oral route of administration for antibiotics that have reliable oral absorption. See page 63. 3. Emergency Department , intensive care units, and cystic fibrosis patients Controlled antibiotics may be prescribed without infectious disease approval for use in the Emergency Department, for use in the Medical and Surgical Intensive Care Units, and for the treatment of cystic fibrosis patients. 9 ANTIMICROBIAL AGENTS ON THE FAHC FORMULARY FOR ADULTS OPEN CRITERIA-BASED CONTROLLED Parenteral Ampicllin Cefazolin Cefuroxime Clindamycin Co-trimoxazole Doxycycline Erythromycin Gentamicin Metronidazole Nafcillin Penicillin G Piperacillin Parenteral Ampicillin / sulbactam Azithromycin Cefotetan Ceftriaxone Levofloxacin Tobramcyin Vancomycin Parenteral Acyclovir *4 Amikacin Amphotericin B deoxycholate Amphotericin B liposome Aztreonam Caspofungin Ceftazidime *1 Cefepime *1 Ciprofloxacin*5 Fluconazole *4 Ganciclovir *3 Itraconazole Linezolid Meropenem *1 Pentamidine Piperacillin / tazobactam Quinupristin / dalfopristin Voriconazole Oral Acyclovir Amoxicillin Amoxicillin / clavulanate Cephalexin Cefpodoxime proxetil Clindamycin Co-trimoxazole Dicloxacillin Doxycycline Erythromycin Isoniazid Ketoconazole Metronidazole Neomycin Nitrofurantoin Nystatin Penicillin VK Rifampin Oral Azithromycin Clarithromycin Famciclovir Levofloxacin Norfloxacin Vancomycin Valacyclovir Oral Ciprofloxacin *5 Dapsone Fluconazole *2, *4 Fosfomycin Ganciclovir *3 Itraconazole Linezolid Ofloxacin Voriconazole Topical Mupirocin * These drugs can be used without ID approval for the specific indications listed below: 1 2 3 4 5 Febrile neutropenic patients (ANC <500) One dose (150 mg) treatment of vaginal candidiasis Renal transplant patients with suspected or documented CMV infection Stem cell patients For prevention of bacterial infections in cirrhotic patients with GI bleeding 10 ANTIMICROBIAL SUSCEPTIBILITY RESULTS FLETCHER ALLEN HEALTH CARE July 1, 2004 through June 30, 2005 Max strains tested Escherichia Enterobacter Klebsiella Proteus Proteus Serratia Acinetobacter Citrobacter Pseudomonas Staphylococcus Coag Coag pos neg Enterococcus*** species species species Mirabilis species species species Freundii Aeruginosa 3088 269 721 218 60 97 34 73 1095 1928 516 805 Streptococcus Pneumoniae % Susceptibile Ampicillin 72 5 1 93 8 14 18* 10 2 ** ** 95 -- Ampicillin/Sulbactam 70 20 78 100 58* 10 -- -- 2 -- -- -- -- Amikacin 99 97 100 -- -- -- -- -- 71 -- -- -- -- Aztreonam 99 83 99 99 95 99 13* 76 81 -- -- -- -- Ceftazidime 99 85 99 100 86 99 73* 73 85 -- -- -- -- Ceftriaxone 99 85 100 100 100 94 38* 74 31 -- -- -- -- Clindamycin -- -- -- -- -- -- -- -- -- # # -- -- Ciprofloxacin 95 97 98 91 92 94 97* 92 71 66 54 70 -- Cefotetan 86 79 97* -- -- -- -- -- 7 -- -- -- -- Cefazolin 97 9 97 98 14 1 0* 6 1 65 35 -- -- Cefepime 99 99 100 97 100 100 -- 100 83 -- -- -- Cephalothin***** 86 -- -- -- -- -- -- -- -- -- -- -- -- Co-trimoxazole 86 94 95 87 88 94 88* 88 15 -- -- -- -- Erythromycin -- -- -- -- -- -- -- -- -- 49 40 -- -- Gentamicin 97 100 100 96 98 100 79* 96 75 -- -- -- -- Imipenem 99 99 100 99 100 99 100* 100 84 -- -- -- -- Meropenem 99 100 100 -- -- -- -- -- 89 -- -- -- -- Oxacillin/Nafcillin -- -- -- -- -- -- -- -- -- 65 -- -- -- Oxacillin/Nafcillin -- -- -- -- -- -- -- -- -- -- 35 -- -- Piperacillin 57 82 100 -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- 91 -- -- -- -- 84 98 99 100 94 94* 83 -- -- -- -- -- Piperacillin Piperacillin/Tazobact 99 Piperacillin/Tazobact -- -- -- -- -- -- -- -- 93 -- -- -- -- Tobramycin 98 100 99 96 100 91 82* 99 88 -- -- -- -- Vancomycin -- -- -- -- -- -- -- -- -- 100 100 99 -- Penicillin 69 (15% Int) Ceftriaxone (CSF) 67 Ceftriaxone (serum) *===<50 strains tested **== At FAHC >90% of Staphylococcus sp. are resistant to penicillin and ampicillin ***== For serious enterococcal infections combination therapy with a beta lactam and an aminoglycoside antibiotic should be used. ****== 66 pneumococcal strains tested against ceftriaxone; only strains NOT susceptible to penicillin in a screening procedure tested against ceftriaxone *****== Cephalothin should be used as the class drug for determining susceptibility to oral first generation cephalos1porins # == Staphylococci and streptococci not tested against erythromycin resistant strains routinely 91 11 AMINOGLYCOSIDE ANTIBIOTICS 1. General principles: a. All aminoglycosides are equally effective against susceptible gram-negative bacteria and cause a similar incidence of toxicity. Gentamicin is the least expensive and is therefore the aminoglycoside of choice for most gram-negative infections. b. For maximum bactericidal effect, doses to achieve high peak serum levels but very low trough levels are employed. This is commonly referred to as once daily aminoglycoside therapy. c. With traditional or high dose aminoglycoside therapy, the incidence of renal or ototoxicity is very low (<5%). In patients who are at high risk for toxicity (see section 4 below), alternative antimicrobials should be considered. d. For serious gram-negative infections the use of aminoglycosides with beta-lactam antibiotics for synergistic effect is encouraged and often necessary to ensure clinical cure. e. Aminoglycoside dosing is based on actual body weight unless the patient is obese then a dosing weight needs to be calculated (see section 3 on page 12). 2. Aminoglycosides on formulary: a. Gentamicin - aminoglycoside of choice for susceptible organisms b. Tobramycin - for gentamicin resistant infections only c. Amikacin - requires ID approval 3. Indications and recommendations for appropriate use: a. Infections due to susceptible gram-negative bacteria b. Use with beta-lactam antibiotic for synergistic effect is recommended for the treatment of the following serious infections: 1. Serious gram-negative infections (Pseudomonas, Enterobacter, Serratia, etc) 2. Serious enterococcal infections 3. Febrile neutropenic patient 4. Patients at increased risk for development of nephrotoxicity and ototoxicity: a. b. c. d. e. f. g. Elderly (decreased renal tubule cell regenerative capacity) Duration of therapy > 1 week (accumulation effect) Prior aminoglycoside therapy within one month Concurrent nephrotoxic drugs (amphotericin B, cyclosporine, etc) Prolonged elevated trough concentrations (accumulation effect) Episodes of excessive diuresis, hypovolemia, or shock (poor renal perfusion) Pre-existing renal or liver disease 5. Relative contraindications to use: a. History of hypersensitivity reactions to aminoglycosides b. History of hearing loss or vestibular dysfunction, particularly in patients with impaired vision and peripheral neuropathy c. Diabetes d. Pre-existing renal or liver disease 12 ONCE-DAILY AMINOGLYCOSIDE THERAPY FOR GENTAMICIN AND TOBRAMYCIN 1. Preferred method for most adult patients (see exclusion criteria under #5 below) 2. Initial dose (see section 2 on page 14 for information on how to calculate creatinine clearance) Creatinine Clearance Dose and Interval >60 ml/minute 7 mg/kg every 24 hours 40 to 60 ml/minute 7 mg/kg every 36 hours 3. Dose based on actual body weight (ABW) unless patient obese (20% over ideal body weight [IBW]). IBW (males) = 50kg + 2.3kg/inch over 5 ft IBW (females) = 45.5kg + 2.3 kg/inch over 5 ft Obese dosing weight = IBW + 0.4(ABW - IBW) 4. Monitoring and dose adjustment: a. Pharmacy will order a single random serum level after the first dose between 6 and 14 hours after the start of the infusion. b. Using nomogram (on following page), serum level will be evaluated by Pharmacy and, if necessary, dose adjustment recommended. c. If treatment continues for more than 5 days, a second random level will be ordered by Pharmacy. d. For patients receiving prolonged therapy or in the intensive care units, serial serum levels will be ordered and evaluated by Pharmacy in order to more accurately individualize the dose. 5. Patients excluded from 7 mg/kg once-daily dosing: a. b. c. d. e. f. Pediatric patients Pregnant patients Patients with estimated CrCl < 40 ml/min Patients with ascites, endocarditis, or severe burn injury Cystic fibrosis patients Patients with dosing intervals > 48 hours per nomogram 13 14 TRADITIONAL AMINOGLYCOSIDE DOSING METHOD For adult patients excluded from once-daily dosing (see section 5 on page 12) 1. Loading dose: Gentamicin 2 mg/kg Tobramycin 2 mg/kg Amikacin 7.5 mg/kg The loading dose should be based on actual body weight (ABW). 2. Maintenance dose: a. Calculate creatinine clearance (standardized to 72 kg): Males = 140 - age Scr Females = 0.85 x Males For patients with a reported serum creatinine of < 1 mg/dl, consider rounding the serum creatinine to 1 mg/dl. This issue may be clinically important in patients > 60 years of age, or in patients with reduced muscle mass resulting from cachexia, malnutrition, or spinal cord injuries b. Find the estimated creatinine clearance on the left hand column of the nomogram which is located on the next page. c. Move to the right along the nomogram to find the desired dosing interval (q8, q12, q24). The maintenance dose will be a percentage of the loading dose. Example: 55 kg 80 year old female with a Scr of 1.3 mg/dl. The loading dose should be 110 mg. The creatinine clearance is 39 ml/min. The maintenance dose should be 100 mg q24. 3. Monitoring and dose adjustment: a. Pharmacy will order peak and trough serum levels within 48 hours of initial dose unless therapy is less than 3 days. b. Based on a pharmacokinetic evaluation of serum levels, pharmacy will recommend a dosing adjustment if necessary. c. Subsequent peak and trough serum levels will be ordered and evaluated by pharmacy at 5 to 7 day intervals. d. It is suggested that a serum creatinine be obtained at least qod while the patient is receiving aminoglycoside therapy. 15 NOMOGRAM FOR CALCULATING AMINOGLYCOSIDE MAINTENANCE DOSE USING TRADITIONAL METHOD PERCENTAGE OF LOADING DOSE REQUIRED FOR DOSE INTERVAL SELECTED CRCl (ml/min.) Half life (hours) 8 hours 12 hours 24 hours > 100 2.5 100% --90 3.1 84 --80 3.4 80 91% -70 3.9 88 -60 4.5 84 -50 5.3 79 -40 6.5 92% 30 8.4 86 25 9.9 81 20 11.9 75 17 13.6 70 < 15 15.1 CONSULT WITH PHARMACIST IF AGE > 60, DO NOT USE 8 HOUR INTERVAL 16 VANCOMYCIN Vancomycin is a glycopeptide antibiotic with activity against gram-positive pathogens (except vancomycin resistant enterococcus). The oral formulation is not appreciably absorbed and should only be used to treat C. difficile colitis if metronidazole cannot be utilized. The parenteral formulation is not excreted into the bowel and therefore cannot be used to treat C. difficile colitis. A. Criteria for vancomycin use: 1. For treatment of serious infections due to beta-lactam resistant gram-positive microorganisms. Clinicians should be aware that vancomycin may be less rapidly bactericidal than beta-lactam agents for beta-lactam susceptible staphylococci. 2. For treatment of infections due to gram-positive microorganisms in patients with serious allergy (ie. anaphylaxis) to beta-lactam antimicrobials. 3. When antibiotic-associated colitis (AAC) fails to respond to metronidazole therapy or if AAC is severe and potentially life-threatening, the use of oral vancomycin is acceptable. The standard dose is 125 mg QID. 4. Prophylaxis, as recommended by the American Heart Association, for endocarditis following certain procedures in patients at high risk for endocarditis. 5. Empiric treatment of presumed nosocomial infection due to gram-positive cocci (such as patients with indwelling catheters) until results of cultures are known. B. Situations in which the use of vancomycin is discouraged: 1. Routine prophylaxis for surgical patients, very low birth-weight infants, and patients on continuous ambulatory peritoneal dialysis. Patients with a history of nonlifethreatening allergic reactions to penicillins can be safely prescribed cephalosporin antibiotics as an alternative. 2. Empiric antimicrobial therapy for a febrile neutropenic patient, unless there is strong evidence at the outset that the patient has an infection due to gram-positive microorganisms (e.g., inflamed exit site of Hickman catheter). 3. Treatment in response to a single blood culture positive for coagulase-negative staphylococcus, if other blood cultures drawn in the same time frame are negative, i.e., if contamination of the blood culture is likely. 4. Continued empiric use for presumed infections in patients whose cultures are negative for beta-lactam-resistant gram-positive microorganisms. 5. Eradication of methicillin-resistant Staphylococcus aureus (MRSA) colonization. 6. Primary treatment of AAC. 17 VANCOMYCIN DOSING AND MONITORING GUIDELINES 1. Dosing for adults The recommended dose of vancomycin is 15 mg/kg (based on actual body weight). The dose should be rounded to the nearest 250 mg increment The dosing interval is dependent upon the estimated creatinine clearance (Clcr)-see below. See section 2 on page 14 for information on how to calculate creatinine clearance. Clcr (ml/min) > 90 70-89 46-69 30-45 20-29 < 20 Hemodialysis Dose 15 mg/kg q12 hrs 15 mg/kg q18 hrs 15 mg/kg q24 hrs 15 mg/kg q36 hrs 15 mg/kg q48 hrs q 3-7 days depending on levels See section 2B 2. Monitoring A. Vancomycin peak and trough levels have not been correlated with either efficacy or toxicity. Therefore, peak and trough levels are generally not indicated. However, consideration may be given to obtaining a vancomycin trough level if the following conditions are present: 1. 2. 3. 4. Patients receiving vancomycin plus an aminoglycoside Patients with rapidly changing renal function Patients with central nervous system infections (meningitis) Patients with endocarditis Vancomycin trough levels can be obtained before the 4th dose in patients with normal renal function. A serum creatinine should be obtained at least twice weekly for patients on vancomycin therapy. B. Hemodialysis Consultation with nephrology or pharmacy is recommended. 1. High Flux Dialyzers Administer 20 mg/kg as a single loading dose followed by 8 mg/kg after each hemodialysis session 2. Conventional Dialyzers Administer 20 mg/kg as a single loading dose. Further doses of vancomycin will depend upon serum levels. C. Peritoneal Dialysis 1. Vancomycin may be administered intraperitoneally (IP). Consultation with nephrology is recommended. 18 GUIDELINES FOR CRITERIA BASED ANTIBIOTICS • • • • • • Ampicillin / sulbactam Azithromycin Cefotetan Ceftriaxone Levofloxacin Norfloxacin 19 19 20 20 21 22 22 AMPICILLIN / SULBACTAM Ampicillin / sulbactam is ampicillin combined with sulbactam which is an inhibitor of microbial beta-lactamase. This spectrum of activity includes beta-lactamase producing strains of E. coli, Klebsiella species, and Bacteroides species. Ampicillin-sulbactam is not active against P. aeruginosa. The standard dose is 3 grams q6h. A. Criteria for ampicillin / sulbactam use: 1. Empiric therapy of community-acquired intra-abdominal infection of moderate severity 2. Type II diabetic foot infections 3. Inpatient treatment of pelvic inflammatory disease with doxycycline 4. Postoperative pelvic cellulitis 5. Mild postpartum endometritis 6. Pre-operative prophylaxis for bowel, biliary, or gynecologic surgery (single dose) B. Situations in which ampicillin / sulbactam use is discouraged: 1. Nosocomial or severe community-acquired intra-abdominal infections 2. Infections not involving the gastrointestinal tract or pelvis such as pneumonia, cellulitis, and urinary tract infections 3. Preoperative prophylaxis for abdominal hysterectomy or cesarean section 4. Postoperative prophylaxis 20 AZITHROMYCIN Azithromycin is a macrolide (azalide) antibiotic with activity against Haemophilus influenzae, Moraxella catarrahlis, and atypical pathogens such as Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, and Legionella pneumophila. Azithromycin is active against erythromycin susceptible Streptococcus pneumoniae and Staphylococcus aureus but erythromycin is more active against these gram-positive cocci. A. Criteria for oral azithromycin: 1. For the management of pulmonary infections caused by atypical pathogens. The standard dose is 500 mg on day 1 followed by 250mg q24h on days 2-5. 2. For single dose therapy of Chlamydia trachomatis; one gram of azithromycin. B. Criteria for intravenous azithromycin : 1. For the management of pulmonary infections caused by atypical pathogens in patients who cannot take oral azithromycin. The standard dose is 500 mg q24h intravenously followed by 500 mg q24h orally to complete a 7-10 day treatment course. The timing of the switch to oral therapy should be done in accordance with clinical response (see section 3 on page 63). CEFOTETAN Cefotetan is a 2nd generation cephalosporin (cephamycin) available only in intravenous form. Concerns have arisen about hemolytic anemia and increasing resistance within anaerobic bacteria. Therefore, caution should be used when considering cefotetan to treat community acquired intraabdominal infections, diabetic foot infections, pelvic inflammatory disease, postoperative pelvic cellulitis, mild postpartum endometritis, and preoperative prophylaxis for bowel, biliary, or gynecologic surgery. The use of cefotetan is discouraged for nosocomial or severe community acquired intra-abdominal infections, infections not involving the gastrointestinal tract or pelvis, preoperative prophylaxis for abdominal hysterectomy or cesarean section, and postoperative prophylaxis. 21 CEFTRIAXONE Ceftriaxone is a 3rd generation cephalosporin available only in parenteral form (IV or IM). It is very active against most gram-negative bacilli excluding Pseudomonas aeruginosa. It is not active against enterococci or anaerobes. The standard dose is 1 gram q24h. A. Criteria for ceftriaxone use: 1. Documented infections due to susceptible: a. gram-negative bacteria resistant to cefazolin, cefotetan, co-trimoxazole, or ampicillin. b. penicillin-resistant pneumococcus (life-threatening) 2. Empiric therapy for the following suspected infections until culture results are available: a. community acquired pneumonia (1 gm every 24 hours) b. nosocomial pneumonia in patients who are non-hypotensive and not in intensive care setting (1gm every 24 hrs) c. serious community-acquired and nosocomial infections when aminoglycoside or co-trimoxazole therapy is inappropriate (1gm every 24hrs) d. community-acquired meningitis (2gm every 12 hrs) e. suspected sepsis in newly admitted pediatric patients > 3 months old and suspected occult bacteremia in outpatients 3 to 36 months old f. uncomplicated gonococcal infection or ambulatory management of PID (250 mg IM x 1) g. primary peritonitis (1gm every 24 hrs) B. Situations in which ceftriaxone use is discouraged 1. 2. . 4. Suspected or documented gram-positive infections Infections due to Enterobacter sp. Endocarditis Continued empiric use: a. when infectious etiology is not felt to be the cause of fever or b. when cultures are positive for organisms sensitive to more narrow spectrum antibiotics or c. when patient is able to take an oral antibiotic 5. Empiric use for patients in septic shock or located in intensive care units. 6. Empiric use for febrile neutropenic patients 22 LEVOFLOXACIN Levofloxacin is a quinolone antibiotic with enhanced activity against gram-positive microorganisms. It is more active than ciprofloxacin against S. pneumoniae. Levofloxacin is active against atypical pathogens such as M. pneumoniae, C. pneumoniae, and L. pneumophila. Levofloxacin is also active against gram-negative bacilli including P. aeruginosa. I. Potential indications for levofloxacin use A. Community acquired pneumonia B. Nosocomial pneumonia II. Dosing Guidelines A. Usual dosing for patients with a creatinine clearance > 50 ml/min. For patients with a lower calculated creatinine clearance please refer to page 71. Indication Dose 1. Community acquired pneumonia 2. Nosocomial pneumonia 500 mg IV / PO q24h 750 mg IV / PO q24h NORFLOXACIN A. Criteria for norfloxacin use: Norfloxacin is a quinolone antibiotic with activity against gram-negative pathogens which includes P. aeruginosa. Norfloxacin is indicated for the treatment of infections confined to the urinary tract. Norfloxacin does not produce blood levels high enough to treat bacteremic patients. 1. For treatment of complicated cystitis and prostatitis in patients unable to take co-trimoxazole. The dose is 400 mg po bid. 23 GUIDELINES FOR CONTROLLED ANTIBIOTICS • • • • Ceftazidime Ciprofloxacin Piperacillin / tazobactam Meropenem 24 24 25 26 27 CEFTAZIDIME Ceftazidime is a third generation cephalosporin. It is the most active cephalosporin against P. aeruginosa. The activity of ceftazidime against gram-positive cocci and anaerobes is poor. For the treatment of P. aeruginosa infections, it is generally recommended that ceftazidime be combined with an aminoglycoside. The decision to add an aminoglycoside for synergy should be based on a risk versus benefit decision. The potential advantage of the combination (synergistic killing coupled with the potential for decreased bacterial resistance) must be weighed against the potential nephrotoxicity and ototoxicity of the aminoglycoside. I. Potential indications for ceftazidime use A. Therapy for documented Pseudomonas aeruginosa infections B. Empiric therapy for hospital / nursing home acquired infections such as: • • • • Nosocomial bacteremia ICU acquired pneumonia or other infection Septic shock Cystic fibrosis C. Empiric therapy in febrile neutropenic patients who do not have a serious allergy (anaphylaxis) to penicillin. If the allergy to penicillin is a rash, ceftazidime may be safely used. II. Situations in which ceftazidime use is discouraged A. Treatment of non-pseudomonal gram-negative or gram-positive infections B. Empiric treatment of community acquired infections III. Dosing guidelines A. Usual dosing for patients with creatinine clearance > 50 ml/min. For patients with a lower calculated creatinine clearance please refer to page 71. Indication Dose 1. Life threatening infections such as pneumonia, ....................2 g q8h bacteremia, neutropenia 2. Urinary tract infections...........................................................500 mg 12h 3. Other systemic infections ......................................................1-2 gm q8h 25 CIPROFLOXACIN Ciprofloxacin is a second generation quinolone with excellent activity against aerobic gramnegative rods including Pseudomonas aeruginosa. Activity against staphylococci and streptococci is less than levofloxacin and trovafloxacin. Ciprofloxacin has no activity against anaerobes. The oral absorption of ciprofloxacin is excellent. As a result, blood levels with the intravenous and oral formulations are similar. FAHC IS EXPERIENCING INCREASING CIPROFLOXACIN RESISTANCE IN PSEUDOMONAS. THIS IS ESPECIALLY TRUE IN THE ICUs. CAUTION IS SUGGESTED. I. Potential indications for ciprofloxacin use: A. Therapy for documented Pseudomonas aeruginosa infections B. Empiric therapy for hospital / nursing home acquired infections such as: • • • • Nosocomial bacteremia ICU acquired pneumonia or other infection Septic shock Intraabdominal infections in combination with an anti-anaerobe and anti-enterococcal agent C. Aerobic gram-negative rod bone infections D. Documented infections due to Enterobacter species. TMP-SMX may be used as an alternative to ciprofloxacin for infections due to Enterobacter species. E. Type II and III diabetic foot infections in combination with an anti-anaerobe II. Situations in which ciprofloxacin use is discouraged A. Treatment of non-pseudomonal gram-negative (except Enterobacter species), grampositive, or anaerobic infections B. Empiric treatment of community acquired infections except for type II and III diabetic foot infections III. Dosing guidelines A. Usual dosing for patients with creatinine clearance > 30 ml/min. For patients with a lower calculated creatinine clearance please refer to page 71. Indication 1. 2. 3. 4. 5. Nosocomial pneumonia Bone and joint Intraabdominal Skin and skin structure Urinary tract Intravenous Dose 400 mg q8h 400 mg q8-12h 400 mg q12h 400 mg q8-12h 200-400 mg q12h 26 Oral Equivalent 750 mg q12h 500-750 mg q12 500 mg q12h 500-750 mg q12 250-500 mg q12 PIPERACILLIN / TAZOBACTAM Piperacillin / tazobactam is piperacillin combined with tazobactam which is an inhibitor of microbial beta-lactamase. This spectrum of activity includes beta-lactamase producing strains of E. coli, Klebsiella species, and Bacteroides species. The addition of tazobactam does not enhance the activity of piperacillin against Pseudomonas aeruginosa. I. Potential indications for piperacillin / tazobactam use A. Nosocomial intraabdominal or pelvic infections in patients who are critically ill or in the intensive care unit. B. Type II and III diabetic foot infections C. Nosocomial pneumonia II. Situations in which piperacillin / tazobactam use is discouraged A. Empiric treatment of community acquired infections B. Type I diabetic foot infections III. Dosing Guidelines A. Usual dosing for patients with creatinine clearance > 50 ml/min. For patients with a lower calculated creatinine clearance please refer to page 71. Indication Dose 1. Intraabdominal infections and diabetic foot infections 3.375 gm q6h 2. Nosocomial pneumonia 4.5 gm q6h 27 MEROPENEM Meropenem is a carbapenem antibiotic with broad activity against aerobic gram negative rods including Pseudomonas, anaerobes, and gram positive bacteria including streptococci, staphylococci and enterococci. I. Potential indications for meropenem use A. Nosocomial polymicrobial infections Intra-abdominal sepsis Complex gynecological infections (page 45) B. Treatment of Pseudomonas C. Infections in patients with cystic fibrosis D. Type III diabetic foot infections E. Necrotizing fasciitis II. Situations in which meropenem use is discouraged A. Community acquired infections B. Infections caused by a single type of bacteria Pneumonia Cellulitis UTI III. Dosing guidelines A. Usual dosing for patients with creatinine clearance > 50 ml/min. For patients with a lower calculated creatinine clearance please refer to page 71. Indication 1. 2. 3. Dose Most indications Pseudomonas infections Meningitis 1g q8h 2g q8h 2g q8h 28 TREATMENT GUIDELINES AND ALGORITHMS FOR SPECIFIC INFECTIONS Community and nosocomial / nursing home acquired pneumonia .... 29-32 Intra-abdominal infections .................................................................. 33-37 Urinary tract infections ....................................................................... 38-39 Diabetic foot infections ....................................................................... 40-41 Fever and neutropenia ....................................................................... 42-43 Female genital tract infections ........................................................... 44-45 Bite wound infections ......................................................................... 46-47 Infectious Diarrhea & C. difficile ......................................................... 48-52 Principles of surgical prophylaxis ....................................................... 53-55 Prevention of bacterial endocarditis ................................................... 56-58 Therapy for selected sexually transmitted diseases .......................... 59-60 Post-exposure prophylaxis................................................................. 61 29 COMMUNITY-ACQUIRED AND NOSOCOMIAL / NURSING HOME PNEUMONIA 1. A sputum gram stain & culture should be obtained in all patients with suspected pneumonia. 2. Most cases of community acquired pneumonia (CAP) are due to S. pneumoniae, Haemophilus influenzae, Moraxella Catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella species. Gram negative bacilli are uncommon pathogens except in nursing home patients. See Figures 1 and 2. 3. For community-acquired pneumonia, a legionella urinary antigen should be obtained. 4. Aspiration pneumonia occurring in the community is generally due to oral anaerobes and can be treated with clindamycin monotherapy. In contrast, aspiration pneumonia occurring in the hospitalized patient is generally due to gram-negative organisms. 5. Most cases of nosocomial pneumonia ( > 48 hours in hospital) are due to gram-negative organisms. Approximately 20-25 % of nosocomial pneumonias are due to Staphylococcus and Streptococcus. Pneumonia acquired in skilled nursing facilities should be considered nosocomial. Pneumonia acquired in the ICU should be considered due to Pseudomonas aeruginosa until proven otherwise. See Figure 3. 6. Regarding hospital acquired pneumonia and ventilator associated pneumonia: Narrow the initial broad spectrum antibiotics to a single agent based on culture and sensitivity. There is no data supporting the use of two antibiotics to treat pneumonia due to Pseudomonas. Using two antibiotics has not been shown to improve outcomes or prevent resistance. Negative sputum cultures (if obtained while the patient has not had a change in antibiotics for the past 72 hours) can be used to discontinue antibiotics. Limit the duration of therapy to 7 days unless Pseudomonas is isolated. If Pseudomonas is isolated, treat for 14 days. 30 COMMUNITY-ACQUIRED PNEUMONIA OUTPATIENT THERAPY Figure 1 SYMPTOMS (+) CHEST X-RAY(+) Sputum Gram stain & culture Not Available Alternatives Preferred Cefpodoxime 1 or Amoxicillin / clavulanate 1 Macrolide 2 or Doxycycline or Levofloxacin 1 No activity against atypical pathogens 2 Erythromycin, azithromycin, clarithromycin 31 COMMUNITY-ACQUIRED PNEUMONIA REQUIRING HOSPITALIZATION Figure 2 SYMPTOMS (+) CHEST X-RAY (+) SPUTUM GRAM STAIN SPUTUM & BLOOD CULTURES (-) If not diagnostic Levofloxacin or Ceftriaxone + Azithromycin Adjust antibiotics based on culture & sensitivity Transition to oral antibiotics If cultures not available Levofloxacin or Cefpodoxime + Azithromycin 32 NOSOCOMIAL PNEUMONIA Figure 3 SYMPTOMS (+) CHEST X-RAY (+) Risk Factors for Multi-Drug Resistant Pathogens? Antibiotic therapy within preceding 90 days Hospitalization > 5 days Hospitalization within previous 90 days Residence in nursing home Chronic dialysis Home wound care Immunosuppressed Yes No Ceftriaxone or Levofloxacin Ceftazidime or Cefepime or Meropenem or Pip-tazobactam + Ciprofloxacin or Levofloxacin +/Vancomycin (If gram-positive cocci are present on sputum gram-stain) Narrow spectrum to a single agent based on culture and sensitivity Negative sputum cultures (if obtained while the patient has not had a change in antibiotics in the past 72 hours) can be used to discontinue antibiotics. Treat for 7 days. If Pseudomonas, treat for 14 days. Reference: American Thoracic Society. Guidelines for the Management of Adults with Hospital-acquired, Ventilatorassociated, and Healtcare-associated Pneumonia. Am J Respir Crit Care Med vol 171. pp 388-416, 2005. 33 ABDOMINAL INFECTIONS 1. Intra-abdominal infections (IAI) include localized peritonitis (see figure 1) such as cholecystitis/cholangitis, diverticulitis, appendicitis, and/or diffuse peritonitis 2. Diffuse Peritonitis can be defined as: • Primary (spontaneous bacterial peritonitis or SBP)-See figure 2 -associated with ascites secondary to cirrhosis -peritoneal fluid with > 250 neutrophils/ml -usually monobacterial • Secondary (See figure 3) - result of perforation of gastrointestinal tract - polymicrobial in nature - need to treat for both aerobic and anaerobic gram-negative bacteria - need surgery consult • Tertiary -persistent infection in seriously ill patients with secondary peritonitis 3. Community-acquired IAI is usually caused by both aerobic gram-negative bacteria (most commonly E. coli but also Proteus and Klebsiella species) and anaerobic gram-negative bacteria (most commonly Bacteroides species). It is not necessary to treat communityacquired IAI with antibiotics with activity against Pseudomonas, Enterobacter, or Enterococcus species. 4. Nosocomial IAI may be caused by more drug resistant gram-negative bacteria such as Pseudomonas, Enterobacter, and Enterococcus due to changes in bacterial flora that occur in an institutional setting. More broad spectrum agents and synergistic combinations may be necessary to treat these infections effectively. 5. Cultures are not needed routinely for community-acquired secondary peritonitis. If cultures are obtained, the microbiology laboratory will perform a limited evaluation unless consulted by the clinician. Fluid or tissue specimens in an anaerobic transport vial should be collected for complicated or tertiary peritonitis and for localized abscesses. 6. See table on page 37 for activities of antimicrobial agents used to treat intra-abdominal infections 34 LOCALIZED PERITONITIS Figure 1 Suspect Localized Infection - Diverticulitis -Female genital tract (pg 44-45) -Appendicitis - Cholangitis / cholecystitis Mild Diverticulitis Admit To Hospital Treat as Out-Patient Surgery Consult ORAL ANTIBIOTICS Co- Trimoxazole + Anti-anaerobe* or Cefpodoxime + Anti-anaerobe or Amoxicillin/ clavulanic Acid or Ciprofloxacin + Anti-anaerobe Moderate (Non-ICU floor) Ampicillin / sulbactam or Severe (ICU) Ceftriaxone + Metronidazole + Ampicillin or Ceftriaxone + Metronidazole or Treat Until Symptoms Resolved Ciprofloxacin + Metronidazole + Ampicillin Ciprofloxacin + Metronidazole or Piperacillin / tazobactam or Meropenem 35 PRIMARY PERITONITIS Figure 2 SUSPECT SBP -Abdominal Pain, Fever -Mental Status Changes -Leukocytosis PARACENTESIS -Cell Count, Differential -Send Peritoneal Fluid for Gram Stain -Inject Peritoneal Fluid Into Both Blood Bottles PMN > 250/mm CEFTRIAXONE 1gm QD ADJUST ANTIBIOTICS BASED ON CULTURE RESULTS 36 Figure 3 SECONDARY PERITONITIS COMMUNITY-ACQUIRED NOSOCOMIAL ADMIT TO HOSPITAL Blood Cultures SURGERY CONSULT Submit Fluid in Sterile Container For Culture SURGERY CONSULT Peritoneal Culture Not Routinely Required MODERATE (NON-ICU FLOOR) SEVERE (ICU) NON-ICU FLOOR Ampicillin-sulbactam or Ceftriaxone + metronidazole or Ceftriaxone + metronidazole + ampcillin or Ciprofloxacin + metronidazole + ampicillin or Ciprofloxacin + metronidazole Piperacillin / tazobactam or Meropenem 37 ICU RELATIVE ACTIVITIES OF ANTIMICROBIAL AGENTS USED TO TREAT INTRA-ABDOMINAL INFECTIONS Aminoglycoside Ampicillin Ampicillin / sulbactam Ceftazidime Cefotetan Ceftriaxone Ciprofloxacin Clindamycin Co-trimoxazole Meropenem Metronidazole Non-Pseudomonas Gram-Negative Aerobes +++ + ++ +++ ++ ++ +++ ++ +++ - Piperacilin Piperacillin / tazobactam Vancomycin Amoxicillin / clavulanate Cefpodoxime + ++ +++ Gram-Negative Anaerobes Psudomonas aeruginosa ++ ++ +++ +++ +++ +++ Enterococcus ++ ++ +++ +++ - - +++ +++ +++ ++ ++ (use w/aminoglycoside) ++ (use w/aminoglycoside) - ++ ++ --- +++ ++ --- --- --- No activity Limited activity Moderate activity High activity 38 ++ ++ + ++ ++ ++ URINARY TRACT INFECTIONS 1. Urine culture can be ordered by three methods: • For most cases, order culture only if urinalysis is abnormal. • Order culture and urinalysis together for symptomatic patients who may not have pyuria (ie. neutropenic patients). • Order culture alone for post-treatment ‘test of cure’, routine pregnancy screening, or prior to urologic procedure. 2. A urinary tract infection is generally defined by the presence of pyuria. Pyuria is defined as greater than 5 WBC’s on microscope or (+) leukocyte esterase. 3. Bacteriuria without signs or symptoms of UTI should not be treated except for: • Pregnant women • Prior to a urologic procedure • Renal transplant patients 4. Elderly patients (>65 years) without signs or symptoms of UTI should not be cultured or treated. Asymptomatic bacteriuria or pyuria is not an indication for treatment. 5. Patients with an indwelling catheter without signs or symptoms of UTI should not be cultured or treated. Asymptomatic bacteriuria or pyuria is not an indication for treatment. 6. Candiduria in catheterized patients does not need to be treated in most cases. Candiduria usually represents colonization, not infection, in these patients. The best approach to eliminate candiduria is to remove the catheter. 7. Recommended empiric antibiotic regimens in order of appropriateness: a. Uncomplicated cystitis in females Cost 1. Co-trimoxazole DS po bid x 3 days..................................... $2.30 2. Nitrofurantoin 100mg po qid x 7 days ............................... $19.00 3. Fosfomycin 3 grams x1 dose ............................................ $26.00 4. Cephalexin 250mg po qid x 3 days ..................................... $8.00 b. Complicated cystitis 1. Co-trimoxazole DS po bid x 7 days 2. Norfloxacin 400mg po bid x 7 days 3. Cefpodoxime 100mg po bid x 7 days c. Pyelonephritis Outpatient 1. Co-trimoxazole DS po bid x 14 days 2. Cefpodoxime 200mg po bid x 14 days 3. Ciprofloxacin 500mg po bid x 14 days Inpatient** ** Transition to oral antibiotics when stable for 24-48 hrs 1. Co-trimoxazole 160mg iv q12 hrs x 14 days 2. Gentamicin +/- ampicillin 1gm iv q6 hrs x 14 days 3. Ciprofloxacin 200mg-400mg iv q12 hrs +/- ampicillin 1gm iv q6 hrs x 14 days 39 MANAGEMENT OF URINARY TRACT INFECTIONS NO SYMPTOMATIC ? NO Culture NO Treatment Except: - pregnancy - prior to urologic procedure - renal transplant YES URINALYSIS microscopic or dipstick POSITIVE FOR PYURIA ? NO YES Does NOT have UTI NO Culture NO Treatment Consider urethritis or vaginitis DETERMINE SEVERITY UNCOMPLICATED CYSTITIS IN FEMALES COMPLICATED CYSTITIS young, healthy, sexually active, without complications symptoms > 7 days abnormal anatomy history of urologic surgery history of renal stones immunocompromised diabetes mellitus pregnancy male patient presence of catheter NO culture Antibiotics see 7a NO followup culture NO urologic evaluation PYELONEPHRITIS additional systemic symptoms such as fever and flank pain Culture urine & blood Antibiotics x 14 days afebrile 24-48 hrs Culture Antibiotics see 7b Followup culture 40 Transition to oral antibiotics Followup culture DIABETIC FOOT INFECTIONS (Special thanks to Dr. Ricci and Vascular Surgery) 1. Soft tissue and bone infection of the lower extremity is the most common cause for hospital admission 2. Usually occur on pressure points of the foot (first metatarsal head) 3. Most diabetic foot infections are polymicrobial (gram-negative rods, anaerobes, and enterococci). This is especially true in type II and III infections-see below. 4. Culture purulent drainage, abscess, or tissue from deep debridement. Do not culture superficial ulcers. 5. Severity of infection is based on clinical exam: • Type I (mild) - Superficial ulceration - Mild erythema of skin - No osteomyelitis - No systemic toxicity - Generally caused by staphylococci and streptococci - Can be treated with oral antimicrobials • Type II (moderate or limb threatening) - Ulceration to deep tissues - Cellulitis around chronic ulcer - Osteomyelitis may be present - May be draining purulent material - Generally polymicrobial - Generally need surgical debridement and intravenous antibiotics • Type III (Severe or limb and life threatening) - Ulceration to deep tissues - Cellulitis - Osteomyelitis usually present - Systemic toxicity - Necrosis/gangrene - Polymicrobial - Need urgent surgical debridement, drainage, or amputation - Intravenous antibiotics 6. Signs of peripheral vascular obstruction Consult vascular surgery if present: - Claudication - Absent pulses - Chronic foot pain - Dependent rubor If the above clinical signs are present, consider work-up with the following: Pulse volume recording (PVR) Ankle-brachial Index (ABI) 41 MANAGEMENT OF DIABETIC FOOT INFECTIONS Clinical Assessment of Infection -Degree of erythema/ purulence -Depth of ulcer -Exposed bone -Extent of necrosis / gangrene ) -Toxicity of patient (fever, leukocytosis) Peripheral Vascular Obstruction X-ray to assess for osteomyelitis especially ftype II and III i f i -PVR -ABI (< 0.7) Angiogra - Type I (Mild) Oral Antibiotics -Dicloxacillin 500 mg q6 or -Cephalexin 500 mg q6h Type II (Moderate) -ID / Surgery -ID / Surgery Consultation -Debridement Consultation -Debridement Admit for IV Antibiotics -Ampicillin / sulbactam or -Ceftriaxone + clindamycin +/- ampicillin or -Clindamycin 300 mg q6h Type III (Severe) Admit for IV Antibiotics -Ceftazidime + clindamycin + Ampicillin or -Ciprofloxacin + clindamycin + Ampicillin or -Ciprofloxacin + clindamycin +/- ampicillin or -Piperacillin / tazobactam or or -Piperacillin / tazobactam 42 -Meropenem FEVER AND NEUTROPENIA * 1. Neutropenia is defined as an absolute neutrophil count (ANC) less than 500/mm3 (some authorities use 1000/mm3 as breakpoint). ANC can be calculated as: ANC = WBC x (% PMNs + % Bands). Fever in a neutropenic patient is defined as temperature > 38.0°C on two occasions or over 38.3°C at any time. 2. Initial empiric antibiotic therapy assumes there is an infection due to aerobic gramnegative bacteria, which is associated with significant mortality in the neutropenic patient. It is not necessary to treat initially for a gram-positive bacterial infection unless there is evidence of a central line infection or cellulitis. 3. Monotherapy with ceftazidime or cefepime has been shown to be as efficacious as ceftazidime + aminoglycoside or cefepime + aminoglycoside. If the patient has a cephalosporin allergy, infectious disease consultation is suggested. 4. Risk of infection can vary in patients with fever and neutropenia and depends on depth and duration of neutropenia, type of malignancy (ie. Leukemia vs solid tumor), and other co-morbid conditions. 5. Patients with neutropenia have an impaired inflammatory response, therefore they may not have typical signs or symptoms of infection. 6. Patients with intravenous catheters should have blood cultures obtained from each port and from a peripheral site prior to initiation of antimicrobial therapy. 7. Use of prophylactic antibacterials, anti-fungals or anti-viral agents is not recommended. An Infectious Disease consultation is recommended for all patients with neutropenic fever especially those with the following conditions: • • • • • Pulmonary infiltrate Central catheter infection Intra-abdominal infection Suspected fungal infection Fever greater than 3 days 2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer. Infectious Diseases Society of America. Clinical Infectious Diseases 2002;34:730-51. 43 MANAGEMENT OF FEVER AND NEUTROPENIA Blood Cultures x 2 Chest X-Ray Order Urinalysis and Urine Culture Together PROMPTLY START EMPIRIC ANTIBIOTICS Ceftazidime or Cefepime or Meropenem Add Vancomycin for: ♦ ♦ ♦ ♦ ♦ 1 – 3 days After 3 days AFEBRILE FEBRILE CONTINUE ANTIBIOTICS NO EVIDENCE OF INFECTION + ANC > 500 Consider switch to oral ciprofloxacin “STABLE” NO EVIDENCE OF INFECTION + ANC > 500 catheter infection cellulitis if on ciprofloxacin prophylaxis (+) blood cultures with gram positive bacteria if hypotensive DIFFERENTIAL DIAGNOSIS ♦ ♦ ♦ ♦ ♦ ♦ ♦ INFECTION IDENTIFIED D/C ANTIBIOTICS IF AFEBRILE 5-7 DAYS Resistant gram-negative bacteria Gram-positive infection Infected catheter Anaerobic infection Drug allergy Viral illness Non-infectious ethiology “UNSTABLE” ANC < 500 INFECTIOUS DISEASE CONSULTATION STRONGLY ENCOURAGED D/C ANTIBIOTICS after 7 DAYS 44 FEMALE UPPER GENITAL TRACT INFECTIONS 1. Female upper genital tract infections (UGTI) covered by these guidelines include postpartum endometritis, postoperative pelvic cellulitis, acute salpingitis, and pelvic abscess. 2. The usual pathogens isolated from patients with UGTI are sexually transmitted pathogens and endogenous organisms that originate from the normal vaginal flora (see below). 3. UGTIs are usually polymicrobial. Anaerobic bacteria predominate numerically and are virtually always present in pelvic abscesses. Multiresistant gram-negative aerobic bacteria are usually not present unless the patient has recently received antibiotics or has undergone prolonged hospitalization. Enterococci are generally not primary pathogens, but may become secondary invaders, accounting for some failures of initial therapy. 4. Gynecologic consultation for all patients admitted with UGTI is recommended. 5. Unless otherwise stated, antimicrobial therapy should be continued until the patient’s temperature has been below 37.5C for 24 hours, she is pain free, and the white blood cell count is normal. For patients with suspected pelvic abscess, potent antianaerobic antibiotic coverage must be included. Drainage (via laparoscopy, laparotomy, or percutaneous catheter) may be necessary. In general, the larger the abscess the less likely it will respond to antimicrobial therapy alone. Abscesses less than 4-5 cm usually respond without drainage, while those larger than 8-10 cm usually require concomitant drainage. USUAL PATHOGENS RECOVERED FROM UGTI Exogenous: Neisseria gonorrhoeae, Chlamydia trachomatis, Streptococcus group A (rare), Mycobacterium tuberculosis (rare) Endogenous: Anaerobic: Peptostreptococcus, Bacteroides fragilis group, Prevotella sp, Clostridium sp, Fusobacteria, Actinomyces (IUD infections), Eubacterium (IUD infections) Aerobic: Streptococcus (groups B, D, and others), Escherichia coli, Klebsiella sp, Gardnerella vaginalis, Mycoplasma hominis 45 FEMALE UPPER GENITAL TRACT INFECTION SUSPECT POSTOPERATIVE PELVIC CELLULITIS OR POSTPARTUM ENDOMETRITIS SUSPECT ACUTE PID Endocervical Culture or Probe for Gonorrhea and Chlamydia MILD BEGIN EMPIRIC THERAPY Ampicillin / sulbactam OUTPATIENT* INPATIENT* or Gentamicin + Clindamycin Ceftriaxone 250mg IM x1 + Doxycycline 100mg BID x 14 days Cefotetan 2gm IV q12 hrs until improved + Doxycycline 100mg bid x 14 days or or Meropenem or Gentamicin + Clindamycin or Ampicillin / Sulbactam 3g q6h + Doxycycline 100mg BID *Reference: Gentamicin + Anti-anaerobe** + Ampicillin Ceftriaxone + Anti-anaerobe** + Ampicillin or Ofloxacin 400mg BID x 14 days + Metronidazole 500mg BID x 14 days SEVERE 2002 Sexually Transmitted Diseases Treatment Guidelines MMWRVol. 51, No. RR 06, May 10, 2002. ** Anti-anaerobe : Metronidazole or Clindamycin 46 BITE WOUND INFECTIONS Each years several million Americans are bitten by animals resulting in approximately 300,000 visits to emergency departments, 10,000 hospitalizations, and 20 deaths. Ninety percent of these bites are from cats and dogs of which 3 to 18 percent of dog bites and 28 to 80 percent of cat bites eventually become infected. 1. Animal and human bite wounds are polymicrobial: Animal: Pasteurella, Staphylococci and streptococci, and anaerobes Human: Staphylococci, streptococci, and anaerobes 2. Bite wounds have the potential to inoculate deep tissue spaces and joints. 3. The following types of wounds are associated with a HIGH RISK of complications: • Bites from cats and humans • Bites to the hand, below the knee, or over a joint • Bite wounds greater than 6-12 hours old • Bite wounds occurring in the elderly, diabetics, or in individuals with prosthetic heart valves or who are immunocompromised Bite wound management: • Aggressive local wound care (clean, debride, irrigate) • See flow diagram for antibiotics • The following wounds are generally not sutured: - Wounds which are not disfiguring - Punctures - Human or cat bites - Bites to the extremities - Wounds which are greater than 6-12 hours old 5. Consider the risk of tetanus • Give tetanus booster if original three dose series has been given, but none in the past 5 years. Give a primary series and tetanus immunoglobulin if patient was never immunized. 6. Consider the risk of rabies a. Investigate the circumstances surrounding the bite and make a decision for the need for rabies vaccination in conjunction with the CDC Rabies Hotline (1-800-Rabies). b. Notify the Vermont Department of Health (Tele # 863-7323) c. Attempt to find, investigate and quarantine all domesticated unvaccinated animals for ten days. Treat patient if animal becomes ill. d. Bites from untraceable domesticated animals require initiation of rabies vaccination e. Bites from untraceable wild carnivores or bats require initiation of rabies vaccination f. Significant exposure to the saliva of a potentially rabid animal even without a bite may require vaccination. Call the Vermont Department of Health with questions (Tele # 863-7323). g. BATS are assumed to be rabid. Bites from rabbits, mice, rats, squirrels, hamsters and guinea pigs almost never call for antirabies prophylaxis. h. If vaccination is required, one dose of the human rabies immunoglobulin (HRIG) and a total of five doses of the human diploid cell rabies vaccine (HDCV) are given as follows: Dose HRIG 20 IU/kg HDCV 1 ml Route If anatomically feasible, the full dose should be infiltrated around the wound(s) and any remaining volume should be administered IM at an anatomic site distant from vaccine administration. IM injection in deltoid area only 47 Time Day 0 Days 0, 3, 7, 14, 28 MANAGEMENT OF BITE WOUND INFECTIONS Identify Circumstances -Human vs Animal -High risk patients (see #3) -Rabies risk Clean, Irrigate, Debride -Neurovascular function -Culture if purulent -Suture (see #4) Consider for all patients requiring hospital admission Consider Vaccination Consultation 1. Tetanus (see #5) 1. Surgery Antibiotics 2. Rabies (see #6) -Orthopedics for hand/joint High risk non-infected wounds 2. Infectious Disease Infected wounds Therapy Prophylaxis (10-14 days) (3-5 days) Primary Alternative Parenteral Parenteral * * If < 8 years, use TMP/SMX ** If < 18 years, use TMP/SMX Ampicillin / sulbactam 1.5 g q6h OR Ceftriaxone 1g q24h + Clindamycin 600mg q8h Oral Amox/ calvulanate 500mg TID 48 Doxycycline 100 mg q12h + Clindamycin 600 mg q8h OR Ciprofloxacin** 400 mg q12h + Clindamycin 600 mg q8h Oral Doxycycline* 100 mg q12h + Clincamycin 300mg q6h OR Ciprofloxacin** 500 mg q12h + Clindamycin 300 mg q6h INFECTIOUS DIARRHEA Gastroenteritis, a term generally used to describe diarrhea with vomiting and abdominal pain, often is due to non-inflammatory infections, but similar symptoms may be due to noninfectious causes. Food-borne disease frequently causes upper gastrointestinal symptoms after a short incubation period, especially from ingestion of pre-formed bacterial toxins (e.g. Staphylococcus aureus and Bacillus cereus). Dysentery is a constellation of symptoms due to infection with an invasive colonic pathogen and includes small-volume stools containing blood and mucus, usually in association with fever and severe abdominal cramping. Most infectious diarrheas are acquired through fecal-oral transmission of pathogens from water, contaminated food, or via person-to-person contact. These infections are: • common and often self-limited illness. • often more severe in the elderly. • more often seen in those with international traveler, those exposed to day care centers, immune compromised hosts, hospitalized patients and those engaging in oral-anal sexual practices. • often non-diagnosed (81% of cases of food-borne disease) • commonly due to Norwalk and Norwalk-like viruses • due to Campylobacter, Salmonella, Shigella and Clostridium perfringens (90% of diagnosed cases of food borne diarrheal illnesses) Table 1: Incubation period, Symptoms and Pathogens Incubation Common symptoms 1-6 hours Nausea, vomiting 8-16 hours Abdominal cramps, diarrhea Nausea, vomiting, diarrhea, descending paralysis Fever, abdominal cramps, diarrhea 8-16 hours 16-48 hours 16-72 hours Associated pathogens and toxins Pre-formed toxins of Bacillus cereus and Staphylococcus aureus Preformed toxins of C. perfringens, B. cereus Clostridium botulinum toxin Salmonella, Shigella, Campylobacter, Vibrio parahemolyticus, Yersinia enterocolitica ETEC , V. cholera and parahemolyticus, Campylobacter, Salmonella, Shigella, Listeria Norwalk and Norwalk-like viruses Abdominal cramps, watery diarrhea 24-48 hours Gastroenteritis, headache 72-120 hours Bloody diarrhea E.coli 0157:H7 ETEC = enterotoxigenic E.coli, E.coli 0157:H7 = enterohemorrhagic E.coli. 49 Table 2: History and Epidemiologic Clues History and Epidemiology History • antacid or H2 blocker use • recent antibiotic use/hospitalization • chronic care facilities • liver disease Epidemiologic risks • travel to a developing region • travel to mountainous areas • contact with children in diapers • • male homosexual diarrhea after social gathering Pathogens • • • • Increased risk for all enteric pathogens C.difficile C.difficile, Aeromonas, viral pathogens Vibrio spp. • Enterotoxigenic E.coli, Shigella, Salmonella, Campylobacter, Giardia, Cholera Giardia, Cyclospora Cryptosporidium, Giardia,Campylobacter, Shigella, Rotavirus, Norwalk virus HSV, N.gonorrhea, Campylobacter, Amebiasis Salmonella, Campylobacter, Norwalk virus, Bacillus cereus, Clostridium perfringens Yersinia enterocolitica Vibrio parahaemolyticus • • • • • contact with domestic and agricultural • animals • consumption of raw and undercooked shellfish HSV = herpes simplex virus, H2 = type 2 histamine • Table 3: Diarrhea Syndromes Syndrome Acute watery diarrhea Colitis, dysentery Proctitis Common symptoms Location Small intestine • large volume stools • cramps Colon • frequent, small stools • tenesmus • blood and mucus • fever, cramps Rectum • same as colitis Persistent (>14days) and Chronic (> 4 weeks) diarrhea • • Small intestine variable, usually and/or colon watery diarrhea. may have signs of weight loss vitamin deficiency Gastroenteritis (food-borne) • • vomiting, nausea watery diarrhea • Stomach, small bowel Select microbial causes Many non-inflammatory enteric pathogens including viruses, Giardia and ETEC Shigella, Campylobacter, Salmonella, E.coli 0157:H7, EIEC, E. histolytica, C. difficile N. gonorrhea, herpes viruses, Chlamydia trachomatis, syphilis Protozoa (Cryptosporidium, Cyclospora, Isospora, Microsporidum), EPEC. Preformed toxins of S. aureus, B. cereus, and viral pathogens. ETEC = enterotoxigenic E. coli, E.coli 0157:H7 = enterohemorrhagic E.coli, EPEC= enteropathogenic E.coli, EIEC =enteroinvasive E. coli 50 Gastroenteritis incubation period (Table 1) risk assessment: •fever •dehydration •toxicity •co-morbidities epidemiologic and clinical clues (Table 2) Acute (< 2 weeks) (Table 3) Persistent (> 2 weeks) Chronic (> 4 weeks) (Table 3) Watery diarrhea, not systemically ill nausea, vomiting ≥ diarrhea •parasitic •small bowel overgrowth •Whipple’s disease •tropical sprue •tuberculosis •non-infectious Viral illness or pre-formed toxin •S. aureus •C. perfringens •B. cereus oral rehydration Systemically ill, inflammatory diarrhea, elderly, immunocompromised No stool cultures2 oral rehydration •Stool O&P X 3 •Acid Fast stain of stool •ELISA for cryptosporidium and giardia fecal leukocytes 1 stool culture2 C.difficile toxin3 symptoms > 714 days if negative, consider Upper endoscopy and biospy Empiric therapy Most patients with acute diarrhea do not need laboratory work-up or antibiotic therapy. Patients with systemic toxicity or inflammatory diarrhea should be rapidly evaluated with fecal leukocytes and cultures. Empiric therapy may be begun, though caution is suggested since some pathogens (E. coli 0157:H7) should not be treated with antibiotics. O&P = ova and parasite, ELISA = enzyme linked immunosorbent 1 fecal leukocytes can be identified by direct stain of the stool or by demonstrating lactoferrin 2 Ova and parasites should be added if risk for exposure to Giardia, homosexual sex or international 3 stool should be sent for C. difficile toxin assay for those who are currently on or recently received antibiotics 51 adjust therapy or discontinue based on results of culture. Therapy for Gastroenteritis Pathogen Bacterial • non-typhoid Salmonella Antimicrobial agent Special circumstances • not recommended routinely • ciprofloxacin 500 mg po bid for 5 days • treat 14 days if immunocompromised. • Campylobacter • oxycycline 500mg po species bid x 5 days for severe disease. • Shigella species • cotrimoxazole DS po bid • treat immunocompromised patient x x 3 days 7-10 days (if sensitive) • ciprofloxacin 500 mg bid x 3 days, if resistant • Escherichia coli ¾ ETEC • ciprofloxacin 1gm po x 1 or • 500 mg po bid x 3 days ¾ E.coli 0157:H7 • not recommended 1 • Yersinia • antibiotics not required • for serious infections or bacteremia: species ciprofloxacin iv or po or • doxycycline with aminoglycoside • Vibrio cholerae • doxycyline 300 mg po x 1 or • ciprofloxacin 1 gm po x 1 Parasitic • Cryptosporidium • no therapy useful • Immunocompromised hosts, try parvum paromomycin 500 mg po tid x 2-4 wks • self limited illness in immune competent hosts • Giardia lamblia • metronidazole 250 mg po tid x 5-10 days • Cyclospora • cotrimoxazole DS bid x 3 cayentanenis days • Isospora belli • cotrimoxazole 2 DS po bid x 2-4 wks 1 increased risk of hemolytic uremic syndrome ETEC = enterotoxigenic E.coli, E. coli 0157:H7 = enterohemorrhagic E.coli DS= double strength 52 TREATMENT OF CLOSTRIDIUM DIFFICILE –ASSOCIATED DIARRHEA General Principles 1. Whenever possible, the offending antibiotic should be discontinued. This alone may lead to resolution of symptoms in up to 20% of cases. 2. Whenever possible, specific therapy should be administered orally. 3. Almost all patients respond to therapy (98%), however relapses are common (5 – 20%). Improvement occurs within 2 – 4 days and treatment should be given for 10 days. 4. Antiperistaltic agents should be avoided since they may precipitate toxic megacolon and reduce fecal concentrations of metronidazole. 5. Routine stool toxin assays following therapy (test-of-cure) are not recommended. Specific Therapy 1. Metronidazole 250 mg po qid or 500 mg po TID x 10 days is the regimen of choice. 2. Vancomycin 125 mg po qid x 10 days is an alternative regimen for patients who are intolerant of, or fail, metronidazole. 3. Relapses can be treated with metronidazole. Patients with multiple relapses may require alternative management strategies. 53 Principles of Surgical Prophylaxis 1. National Research Council Wound Classification Clean - Elective, not emergent, nontraumatic, primarily closed; no acute inflammation; no break in technique; gastrointestinal, biliary and genitourinary tracts not entered. Examples of clean procedures include the following: • Cardiothoracic, vascular, and neurosurgery • Inguinal hernia repair • Insertion of prosthetic material (joint, heart valve, gortex, pacemaker) - Likely pathogens: S. aureus and S. epidermidis Clean-contaminated - Urgent or emergency case that is otherwise clean; elective opening of respiratory, gastrointestinal, biliary or genitourinary tract with minimal spillage not encountering infected urine or bile; minor technique break. Examples of clean-contaminated procedures include the following: • Colorectal surgery, biliary tree surgery, appendectomy • Head and neck surgery, gynecologic surgery • Burns • Gastric surgery in patients treated with H2 blockers, antacids, or proton pump inhibitors • Small bowel obstruction requiring open decompression - Likely pathogens: For head and neck procedures, streptococci and anerobes. For colorectal and biliary tract procedures, gram-negative rods,anaerobes, streptococci, and enterococci. Contaminated Nonpurulent inflammation; gross spillage from gastrointestinal tract; entry into biliary or genitourinary tract in the presence of infected bile or urine; major break in technique. Examples of contaminated surgeries include the following: • Penetrating trauma < 4 hours old • Chronic open wounds to be grafted or covered • Perforated appendix - Likely pathogens: Gram-negative rods, anaerobes, enterococci, staphylococci, and streptococci Dirty - Purulent inflammation (eg. Abscess); preoperative perforation of respiratory, gastrointestinal, biliary or genitourinary tract. Examples of dirty surgeries include the following: • Perforated viscus • Penetrating trauma > 4 hours old - Likely pathogens: Gram-negative rods, anaerobes, enterococci, staphylococci, and streptococci 54 Principles of Surgical Prophylaxis Prophylactic antibiotics A. Dose - The prophylactic dose should be equivalent to the standard therapeutic dose. Agent Recommended Dose Cefazolin Vancomycin Clindamycin Gentamicin Metronidazole 1 gram * 15 mg/kg 900 mg 1.5 mg/kg 500 mg * Consider 2 grams for CABG and orthopedic procedures B. Timing - The prophylactic parenteral dose should be completely administered within 60 minutes or less prior to the incision. C. Duration - Post-operative administration of antibiotics is not advised. If used, the duration of post-operative antibiotics should be discontinued within 24 hours after surgery end time. If established infection is found at the time of the operation, treatment should be continued as clinically indicated. D. Repeated doses during the surgical procedure REDOSE THIS DRUG IF SURGERY LASTS LONGER THAN: Cefazolin..............................................2-4 hours Aminoglycosides..................................2-4 hours Clindamycin .........................................3-6 hours E. Luminal antibiotics for colorectal procedures (to be used in addition to the parenteral antibiotics listed under the colorectal section of the algorithm) - One gram of oral erythromycin base and one gram of oral neomycin are given at 1 p.m., 2 p.m., and 11 p.m. the day before surgery. 55 Surgical Prophylaxis Clean Cefazolin or Vancomycin * Head & Neck ** Gastric Dirty / Contaminated Clean - Contaminated OB GYN Cefazolin or Clindamycin +/Gentamicin * Colorectal Biliary (-) cholangitis Cefazolin +/- Metronidazole OR Clindamycin * * For patients allergic to cephalosporins or with anaphylaxis to penicillin ** Some authorities would add gentamicin for major head and neck procedures 56 (+) cholangitis Cefazolin + Metronidazole OR Gentamicin + Clindamycin * PREVENTION OF BACTERIAL ENDOCARDITIS American Heart Association Committee Report. Prevention of bacterial endocarditis. JAMA 1997;277:1794-801. 1. Endocarditis prophylaxis is recommended for the following cardiac conditions: High risk category • Prosthetic cardiac valves, including bioprosthetic and homograft valves • Previous bacterial endocarditis • Complex cyanotic congenital heart disease (eg, single ventricle states, transposition of the great arteries, tetralogy of Fallot) • Surgically constructed systemic pulmonary shunts or conduits Moderate risk category • Most other congenital cardiac malformations (other than above and below) • Acquired valvar dysfunction (eg, rheumatic heart disease) • Hypertrophic cardiomyopathy • Mitral valve prolapse with valvar regurgitation and/or thickened leaflets 2. Endocarditis prophylaxis is recommended for the following dental procedures if the conditions under #1 are present: For other procedures, endocarditis prophylaxis is not indicated. • Dental extractions • Periodontal procedures including surgery, scaling and root planing, probing, and recall maintenance • Dental implant placement and reimplantation of avulsed teeth • Endodontic (root canal) instrumentation or surgery only beyond the apex • Subgingival placement of antibiotic fibers or strips • Initial placement of orthodontic bands but not brackets • Intraligamentary local anesthetic injections • Prophylactic cleaning of teeth or implants where bleeding is anticipated 3. Other procedures where endocarditis prophylaxis is recommended if the conditions under #1 are present. For other gastrointestinal, genitourinary, and respiratory procedures, prophylaxis is not indicated. Respiratory tract • Tonsillectomy and/or adenoidectomy • Surgical operations that involve respiratory mucosa • Bronchoscopy with a rigid bronchoscope Gastrointestinal tract • Sclerotherapy for esophageal varices • Esophageal stricture dilation • Endoscopic retrograde cholangiography with biliary obstruction • Biliary tract surgery • Surgical operations that involve intestinal mucosa Genitourinary tract • Prostatic surgery • Cystoscopy • Urethral dilation 57 PREVENTION OF BACTERIAL ENDOCARDITIS Table 1. Recommended prophylactic regimens for dental, oral, respiratory tract, or esophageal procedure Situation Agent Regimen Standard general prophylaxis Amoxicillin 2g PO 1 hr before the procedure Unable to take oral 2g IV/IM within 30 min before the Ampicillin medications Allergic to penicillin procedure Clindamycin 600mg PO 1 hr before the procedure or Cephalexin 2g PO 1 hr before the procedure or Azithromycin 500mg PO 1 hr before the procedure Allergic to penicillin and Clindamycin 600mg IV within 30 min before the unable to take oral or procedure medications Cefazolin 1g IV/IM within 30 min before the procedure Table 2. Recommended regimens for genitourinary gastrointestinal (excluding esophageal) procedures Situation High-risk Patients Agents Regimen Ampicillin plus Ampicillin 2g IV/IM plus gentamicin IV/IM gentamicin 1.5mg/kg (not to exceed 120 mg) within 30 min of starting the procedure; 6 hr later, ampicillin 1g IM/IV or amoxicillin 1g PO High-risk patients allergic to Vancomycin plus Vancomycin 1g IV plus gentamicin IV/IM ampicillin/amoxicillin gentamicin 1.5mg/kg (not to exceed 120 mg). Complete infusions within 30 min of starting the procedure. Moderate-risk patients Amoxicillin or Amoxicillin 2g PO 1 hr before the procedure, ampicillin or ampicillin 2g IV/IM within 30 min of starting the procedure Moderate-risk patients allergic to ampicllin/amoxicillin Vancomycin Vancomycin 1g; complete infusion within 30 min of starting the procedure. 58 ENDOCARDITIS PROPHYLAXIS Is patient at Risk ? No Prophylaxis NO (see #1) YES (High vs Moderate Risk) Type of Procedure Genitourinary / Gastrointestinal procedure requiring prophylaxis Dental, Oral, Respiratory, (See # 3) or esophageal procedure (See #2 and #3) NO No Prophylaxis* YES NO YES Moderate No Prophylaxis* High Risk Select Antibiotics Risk (Table 1) Select Antibiotics Select Antibiotics (Table 2) (Table 2) *Prophylaxis is optional for high risk patients undergoing: Flexible bronchoscopy, transesophageal echocardiography, endoscopy with or without gastrointestinal biopsy, vaginal hysterectomy, and vaginal delivery 59 THERAPY FOR SELECTED SEXUALLY TRANSMITTED DISEASES Reference: 2002 Sexually Transmitted Diseases Treatment Guidelines MMWR Vol. 51, No. RR-06, May 10, 2002 1. Genital Herpes Simplex Virus A) First Clinical Episode • Acyclovir 400 mg PO TID or 200 mg 5x/d for 7-10 days. • Famciclovir 250 mg PO TID for 7-10 days • Valacyclovir 1 gram PO BID for 7-10 days B) Recurrent Episodes - Episodic Treatment • Acyclovir 400 mg PO TID or 200 mg 5x/d for 5 days • Acyclovir 800 mg PO BID x 5 days • Famciclovir 125 mg PO BID for 5 days • Valacyclovir 500 mg PO BID for 3-5 days • Valacyclovir 1 gram PO QD x 5 days - Suppressive Therapy • Acyclovir 400 mg PO BID • Famciclovir 250 mg PO BID • Valacyclovir 500 mg QD or 1000 mg QD 2. Syphilis * A) Primary, secondary and early latent • Benzathine penicillin G 2.4 million units IM as a single dose • Doxycycline 100 mg PO BID for 14 days • Tetracycline 500 mg PO QID for 14 days • Ceftriaxone 1 gram IM for 8-10 days (limited data to support this regimen) • Erythromycin 500 mg PO QID for 14 days B) Late latent, unknown duration, tertiary • Benzathine penicillin G 2.4 million units IM weekly x 3 • Doxycycline 100 mg PO BID for 28 days • Tetracycline 500 mg PO QID for 28 days C) Neurosyphilis • Penicillin G 3-4 million units IV q4h for 10-14 days • Procaine penicillin 2.4 million units IM QD plus probenecid 500 mg QID for 10-14 days +/- benzathine penicillin 2.4 million units IM at the end of therapy * Penicillin is the preferred drug for treatment of all stages of syphilis. Data to support the use of alternatives to penicillin (in the presence of penicillin allergy) is limited. 60 THERAPY FOR SELECTED SEXUALLY TRANSMITTED DISEASES 3. Urethritis and Cervicits A) Non-gonococcal urethritis, mucopurulent cervicitis • Azithromycin 1 gram PO x 1 dose • Doxycycline 100 mg PO BID for 7 days • Erythromycin 500 mg PO QID for 7 days • Ofloxacin 300 mg PO BID for 7 days B) Gonococcal Infection - Uncomplicated • Cefixime 400 mg PO x 1 dose • Ceftriaxone 125 mg IM x 1 dose • Ciprofloxacin 500 mg PO x 1 dose • Ofloxacin 400 mg x 1 dose • Plus: Azithromycin 1 gram x 1 dose or Doxycycline 100 mg PO BID for 7 days Disseminated • Ceftriaxone 1 gram IV/IM q24. Once clinically improved, switch to oral cefpodoxime 200 mg q12 to complete a 7 day course. • Ciprofloxacin 400 mg IV q12. Once clinically improved, switch to oral ciprofloxacin 500 mg q12 to complete a 7 day course. 61 Management of Exposures to Bloodborne Pathogens in Healthcare 1. Promptly report an exposure to the FAHC Employee Health office. Please telephone Employee Health (7-1300) and FAX the “Employee Report of Event” form (7-5105). Do not wait to call, or report exposures by snail mail. After 4 p.m. and on weekends and holidays, promptly seek care in the Emergency Department, leave a telephone message and FAX with Employee Health, and follow-up with Employee Health the next business day. 2. “Bloodborne pathogens” include HIV, hepatitis B and hepatitis C. 3. An “exposure” is defined as a percutaneous injury or contact of mucosa or nonintact skin with blood, tissue, or potentially contagious body fluids (blood, fluid with visible blood, semen, vaginal secretions, CSF, synovial, pleural, peritoneal, pericardial and amniotic). Fluids not usually considered infectious include feces, nasal, saliva, sputum, sweat, tears, urine, and vomit – unless they are bloody. For human bites, both the biter and the bitten are considered exposed. 4. Estimated risk of infection following percutaneous exposure: a. Hepatitis B: may exceed 30% (depends on e antigen status of host and assumes b. healthcare worker not immune from vaccination or prior infection). c. Hepatitis C: approximately 2%. d. HIV: approximately 0.3%. 5. Prompt first aid, reporting, evaluation, counseling, treatment, and follow-up are all important following an exposure. 6. Prevention is always the best strategy. All healthcare workers who may have contact with blood, body fluids, or sharps should be vaccinated against hepatitis B and have serologic evidence of response to the vaccine. Handwashing, the proper use and disposal of sharps, and the appropriate use of personal protective equipment are the best ways to reduce exposures. Never recap needles! The user of a sharp is responsible for it’s disposal. 7. Wounds and skin that have been exposed should be washed with soap and water. Mucous membranes should be flushed with water. 8. The Employee Health office will coordinate obtaining consent and testing the source patient for all 3 pathogens as soon as possible. Please do not order source patient testing yourself. A rapid HIV test will be performed whenever possible. 9. Post-exposure treatment will be coordinated by Employee Health, the Emergency Department, the Infectious Diseases Unit, and Pharmacy. 10. Records of employee exposures, testing, and management are confidentially maintained in the Employee Health office and do not become part of the employee’s medical record. Confidentiality must be maintained for healthcare workers and source patients. 11. Exposures to HIV, and decisions about antiretroviral therapy, should be discussed with the Infectious Diseases attending on call. 12. Summary of key points: a. Practice prevention – hepatitis B vaccination, handwashing, proper use of sharps, proper use of protective equipment (gloves, gowns, eye protection) b. Understand what constitutes an exposure c. Prompt reporting of exposures d. Let Employee Health consent and test source patients and employees e. Maintain confidentiality. 62 ORAL ANTIMICROBIAL THERAPY Introduction .............................................62 Selected agents ......................................63-66 -Amoxicillin / clavulanate.................64 -Azithromycin ..................................64 -Cefpodoxime..................................65 -Ciprofloxacin ..................................65 -Levofloxacin...................................66 -TMP/SMX ......................................66 Intravenous to oral switch table ..............67 Costs to patients .....................................68-69 63 ORAL ANTIMICROBIAL THERAPY 1. The historical preference for the intravenous administration of antibiotics has been reevaluated in light of the availability of oral agents with reliable oral absorption. These antimicrobials produce adequate blood levels following oral administration. In addition, the oral route of administration avoids intravenous therapy which is associated with potentially serious complications. The literature is replete with evidence that an early switch or the initial use of oral antibiotics can result in a decreased risk of line infection, decreased hospitalization, and decreased length of stay if admission is required. Such outcomes as these will undoubtedly benefit the entire health care system. 2. The following agents have reliable absorption (good bioavailability). Therefore, these medications should be given orally whenever a patient can take oral medication and has a functional GI tract. • • • • • • • • • Ciprofloxacin* Levofloxacin* Trovafloxacin* Azithromycin* Clindamycin Metronidazole TMP/SMX* Doxycycline Fluconazole ----------------• Amoxicillin / clavulanate* • Cefpodoxime* Oral formulation only 3. Consideration should be given to an early switch to one of the above agents if the following clinical conditions are present: - The patient has a functional gastrointestinal tract and is able to take oral medication - The patient is clinically stable or improving (decreasing temperature, WBC, etc.) - There is an equivalent or appropriate oral agent available (see the above list of oral antibiotics) * These agents are reviewed alphabetically in the next section. Information that is provided includes: Antibiotic class Spectrum of activity Clinical uses Dosage adjustment in renal dysfunction Warnings 64 Selected Oral Agents Amoxicillin / Clavulanate Class Beta-lactam / beta-lactamase inhibitor combination Spectrum of Activity Beta-lactamase producing staphylococci and enterococci Streptococci including Streptococcus pneumoniae H. influenzae and M. catarrhalis Some aerobic gram-negatives including E. coli, Klebsiella, and Proteus species Anaerobic gram-negatives including B. fragilis Pasteurella species Possible Uses Animal bite wounds Mixed infections involving aerobes and anaerobes such as diverticulitis and diabetic foot infections Usual Dose 500 mg TID or 875 mg BID Dose adjustment required in renal insufficiency ? YES Warnings / Side Effects Previous hypersensitivity to any penicillin /-GI upset especially diarrhea Azithromycin Class Macrolide (Azalide) Spectrum of Activity Staphylococci* and streptococci* including Streptococcus pneumoniae H. influenzae and M. catarrhalis Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila No activity against enteric gram-negatives and anaerobes GI upset * Not a drug of choice for staphylococci and streptococci Possible Uses Community acquired pneumonia and uncomplicated soft-tissue infections Exacerbation of COPD Otitis Media Single dose therapy for nongonococcal urethritis (chlamydia). The dose is 1 gram. Usual Dose 500 mg on day 1 followed by 250 mg q24 on days 2-5 Dose adjustment required in renal insufficiency ? NO Warnings / Side Effects Previous hypersensitivity to azithromycin, erythromycin , or any other macrolide antibiotic 65 Cefpodoxime Class Third generation cephalosporin Spectrum of Activity Staphylococci and streptococci including Streptococcus pneumoniae H. influenzae and M. catarrhalis Other aerobic gram-negatives including E. coli, Klebsiella, and Proteus mirabilis No activity against anaerobes, P.aeruginosa. Enterobacter, Serratia, or Enterococcus species Possible Uses Community acquired pneumonia, urinary tract infections, and uncomplicated soft tissue infections Exacerbation of COPD Otitis Media Single dose (200 mg) for gonococcal urethritis Completion of antimicrobial therapy in patient who have been stabilized on ceftriaxone Usual Dose 200 mg BID for community acquired pneumonia Dose adjustment required in renal insufficiency ? YES Warnings / Side Effects Previous hypersensitivity to cefpodoxime, cephalosporins, or penicillins GI upset Ciprofloxacin Class Quinolone Spectrum of Activity Aerobic gram-negatives including P. aeruginosa Poor activity against streptococci and anaerobes Staphylococci and methicillin resistant Staphylococcus aureus (MRSA) are frequently resistant Possible Uses Gram negative infections resistant to TMP/SMZ and cephalosporins Gram negative infections of the bone and joint Travelers' diarrhea Usual Dose 500 to 750 mg BID Dose adjustment required in renal insufficiency ? YES Warnings / Side Effects Previous hypersensitivity to ciprofloxacin or other quinolones Not recommended in children < 18 years of age Not recommended in pregnant women or nursing mothers GI upset 66 Levofloxacin Class Quinolone Spectrum of Activity Staphylococci and streptococci including Streptococcus pneumoniae Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila Aerobic gram-negatives including P. aeruginosa. Possible Uses Community acquired pneumonia Nosocomial pneumonia Usual Dose 500 mg q24 for community acquired pneumonia 750 mg q24 for nosocomial pneumonia Dose adjustment required in renal insufficiency ? YES Warnings / Side Effects Previous hypersensitivity to ciprofloxacin or other quinolones Not recommended in children < 18 years of age Not recommended in pregnant women or nursing mothers Trimethoprim-Sulfamethoxazole (TMP / SMX or Co-trimoxazole) Class Folate antagonist Spectrum of Activity Limited activity against staphylococci, streptococci including Streptococcus pneumoniae, and H. influenzae -M. catarrhalis Some aerobic gram-negatives including E. coli, Klebsiella, Proteus, Enterobacter, and Serratia species Pneumocystis carinii, Listeria and Legionella species Possible Uses Non-ICU nosocomial pneumonia Urinary tract infections Usual Dose One double strength (DS) tablet BID Dose adjustment required in renal insufficiency ? YES Warnings / Side Effects Previous hypersensitivity to sulfonamides or trimethoprim Contraindicated in pregnant and lactating women Rash and GI upset Bone marrow suppression with high doses 67 INTRAVENOUS TO ORAL SWITCH TABLE Intravenous Antimicrobial Oral Equivalent 1 Oral Dose Ampicillin Amoxicillin 500mg q8h Ampicillin / Sulbactam Amoxicillin / Clavulanate 875mg BID Cefazolin Cephalexin 500mg q6h Cefotetan Amoxicillin / Clavulanate or Cefpodoxime+ Metrondiazole 875mg BID or 200mg BID+ 500mg TID Ceftazidime Ciprofloxacin 500 mg BID 2 Ceftriaxone Cefopodoxime 200mg BID Ciprofloxacin Ciprofloxacin 500mg BID 2 Clindamycin Clindamycin 300mg QID Levofloxacin Levofloxacin 500mg q24h 3 1 Antibiotic therapy should be based on sensitivity data if available. 2 For P. aeruginosa, 750mg BID is recommended. 3 For nosocomial pneumonia, 750mg q24h is recommended 68 ANTIMICROBIAL COSTS ORAL ANTIMICROBIAL AGENTS: TYPICAL RETAIL COST TO PATIENTS FOR 10-DAY PRESCRIPTION Antibiotic Dose (mg) Doses/ Day Cost($)/ 10 Days Antibiotic Beta-Lactams Dose (mg) Doses/ Day Cost($)/ 10 Days 200 2 96.00 Beta-Lactams Penicillin VK 250 500 4 4 6.30 9.20 Amoxicillin 250 500 3 3 8.00 11.00 Amoxicillin/clavulanate (Augmentin) 250 500 3 3 69.50 113.00 Dicloxacillin 250 500 4 4 25.00 43.00 Erythromycin base 250 500 4 4 8.50 14.00 Cephalexin (Keflex) 250 500 4 4 21.00 30.00 Erythromycin base 333 3 10.00 Cefadroxil (Duricef) 500 1000 1 1 44.00 86.00 Erythromycin ethylsuccinate (EES) 400 4 17.00 Cefaclor (Ceclor) 250 500 3 3 44.00 108.00 Clarithromycin (Biaxin) 250 500 2 2 81.00 81.00 Cefuroxime (Ceftin) 250 500 2 2 89.00 163.00 Azithromycin ** (Zithromax) 250 1 Loracarbef (Lorabid) 200 200(2) 2 2 87.00 170.00 ** 1st Dose is 500mg 250 500 2 2 74.00 142.00 Cefprozil (Cefzil) Cefpodoxime (Vantin) Macrolides 69 51.00/6 (5 days) Antibiotic Dose (mg) Doses/ Day Cost($)/ 10 Days Antibiotic Sulfonamides and Trimethoprim Dose (mg) Doses/ Day Cost($)/ 10 Days Urinary Tract Infections Only SS DS 2 2 8.00 8.50 Nitrofurantoin (Macrodantin) (Macrobid) 50 100 100 4 4 2 30.00 60.00 35.00 Sulfadiazine (Microsulfon) 500 500(2) 4 4 25.00 50.00 Methenamine (Mandelamine) 1000 4 35.00 Sulfisoxazole (Gantrisin) 500 500(2) 4 4 10.00 17.00 Miscellaneous Trimethoprim 100 2 9.10 Tetracycine 250 500 4 4 5.50 6.40 Doxycycline (Vibramycin) 100 100 1 2 8.00 12.00 Co-Trimoxazole (Bactrim,Septra) Fluoroquinolones Norfloxacin (Noroxin) 400 2 69.00 Minocycline 100 2 27.00 Ciprofloxacin (Cipro) 250 500 750 2 2 2 84.00 90.00 124.00 Clindamycin (Cleocin) 150 150(2) 4 4 24.00 4000.00 Ofloxacin (Floxin) 200 300 400 2 2 2 82.00 97.00 102.00 Metronidazole (Flagyl) 250 4 13.00 Lomefloxacin (Maxaquin) 400 1 91.00 Vancomycin (Vancocin) 125 250 4 4 269.00 501.00 Enoxacin (Penetrex) 400 2 75.00 70 ANTIBIOTIC PRESCRIBING Antibiotic dosing in renal insufficiency.................. 71 Antimicrobial drug interactions ............................. 72-73 Antimicrobials in pregnancy ................................. 74-75 71 RECOMMENDED ANTIMICROBIAL DOSAGE IN RENAL IMPAIRMENT Antimicrobial Agent Acyclovir Dosing Range 5-10 mg/kg q8 Acyclovir PO Amphotericin B 30-50 100% q12 Doses for Renal Failure: Crcl (ml/min) 10-30 100% q24 < 10 50% q24 200-800 mg 5x/day 100% 100% q8 100% q12 0.5-1 mg/kg q24 100% 100% 100% Amoxicillin 250-500 mg q8 100 % q8 100 % q12 100 % q24 Amoxicillin / clavulanate 250-500 mg q8 100 % q8 100 % q12 100 % q24 Ampicillin 1-2 gm q4-6 100% q8 100% q8-12 100% q12-16 1.5 to 3 gm q6h 100% q6-8 100% q12 100% q24h Azithromycin PO 500 mg on day 1 then 250 mg on days 2-5 100 % 100 % 100 % Azithromycin IV 500 mg q24 100 % 100 % 100 % Ampicillin / sulbactam Aztreonam 1-2 gm q8 100% 100% q12 100% q24 Cefazolin 1-2 gm q8 100% q12 50% q12 50% q24 Cefotetan 1-2 gm q12 100% 100% q24 100% q48 Cefpodoxime proxetil 200 mg q12 100% 100% q24 100% q24 Ceftazidime 1-2 gm q8 100% q12 100% q24 50% q24 Ceftriaxone a 1 gm q24 (see footnote) 100% 100% 100% 750 mg q8 100% 100% q12 100% q24 Cefuroxime Cephalexin PO 250-500 mg q6 100% 100% q8-12 50% q12 Ciprofloxacin IV 200-400 mg q12 100% 100% q18 100% q24 Ciprofloxacin PO 500-750 mg q12 500 mg q12 500 mg q18 500 mg q24 Clindamycin 600-900 mg q8 100% 100% 100% Clindamycin PO 150-450 mg q6 100% 100% 100% Co-trimoxazole IV (80mg TMP/5ml) 10-20 ml q12 (10 ml = 1 double strength tablet) 100% 50% q12 50 % q24 b Co-trimoxazole PO 1 double strength q12 100% 1 single strength q12 1 single strength q24 b Doxycycline IV/PO c 100mg q12-24 100% 100% 100% Fluconazole IV/PO c 200-400 mg q24 50% q24 50% q24 50% q48 Ganciclovir (induct) 5mg/kg q12 50% q24 25% q24 500 mg q24 Crcl 20-49 use 500 mg x1 then 250 mg q24h; Crcl 1019 use 500mg x1 then 250mg q48h. 500 mg x1 then 250 mg q48 Crcl 20-49 use 750 mg q48; Crcl 10-19 use 750 mg x1 then 500 mg q48 750 mg x1 then 500 mg q48 Levofloxacin IV/PO c Levofloxacin IV/PO c 750 mg q24 d Meropenem Metronidazole IV/PO 1 gm q8 c 100 % q12 50 % q12 50 % q24 100% q8-12 500 mg q8 100% 100% 1-2 gm q4-6 100% 100% 100% Penicillin G 1-2 million units q4-6 e 100% q6 100% q6-8 100% q8-12 Piperacillin 3-4 gm q6 100% q8 100% q8-12 100% q12 Nafcillin Piperacillin / tazobactam 3.375 gm q6 Crcl > 40 use 3.375 gm q6; Crcl 20-40 use 2.25 gm q6; Crcl < 20 use 2.25 gm q8 Piperacillin / tazobactam 4.5 gm q6h f Crcl > 40 use 4.5 gm q6; Crcl 20-40 use 3.375 gm q6; Crcl < 20 use 2.25 gm q6 a For CNS infections, the dose of ceftriaxone is 2 grams q12h. Not recommended for creatinine clearance of less than 15 ml/min c Intravenous and oral dosing regimens are identical d Recommended dose for nosocomial pneumonia e For CNS infections, the dose of penicillin G is 4 million units q4h f Recommended dose for nosocomial pneumonia b 72 IMPORTANT DRUG INTERACTIONS WITH ANTIBIOTICS Antibiotic Interacting Drug Effect Management Phenytoin Warfarin Increased plasma levels of interacting drug due to decreased clearance Avoid interaction or monitor closely for toxicity Oral Sulfonylureas Chlorpropamide Glipizide Glyburide, etc Increased hypoglycemic effect due to decreased protein binding of interacting drug Avoid interaction or monitor for hypoglycemia Antacids Decreased absorption of doxycycline Separate by at least 2 hrs Warfarin Potentiation of anti-coagulant effect Avoid or monitor INR closely Fluconazole Itraconazole Voriconazole Cyclosporine Oral Sulfonylureas Phenytoin Warfarin Increased plasma levels of interacting drug due to inhibition of Cytochrome P450 oxidase system Avoid interaction or decrease dose of interacting drug by 25 to 50%. Monitor closely. Fluoroquinolones Ciprofloxacin Levofloxacin Norfloxacin Levofloxacin Al , Ca , Mg products (antacids, etc) ++ Multivites w/ Zn Significant decrease in absorption of antibiotic Avoid or give interacting drug at least 6 hrs before or 2 hrs after FQ Sucralfate Significant decrease in absorption of antibiotic Avoid entirely Theophylline Caffeine Increase in plasma levels of theophylline and caffeine Decrease dose of interacting drug by 50% and monitor Benzodiazepines Midazolam Triazolam Carbamazepine Cyclosporine Theophylline Warfarin Increased plasma levels of interacting drug due to inhibition of CYP3A enzymes of Cytochrome P450 oxidase system Avoid interaction or decrease dose of interacting drug by 25 to 50%. Co-trimoxazole Doxycycline Ciprofloxacin Enoxacin Norfloxacin Macrolides Erythromycin Clarithromycin ++ ++ ++ 73 Monitor closely. Antibiotic Macrolides Erythromycin Clarithromycin Metronidazole Rifampin Rifabutin Interacting Drug Effect Management Cisapride Nonsedating antihistamines: Astemizole Loratidine Terfenadine Increased plasma levels of interacting drug due to inhibition of CYP3A enzymes of Cytochrome P450 oxidase system Absolute contraindication due to life threatening arrhythmias Digoxin Increased digoxin levels due to decreased gut metabolism in 10% of population Monitor for digoxin toxicity Alcohol Inhibits alcohol dehydrogenase causing disulfiram-like effect Avoid alcoholcontaining products Warfarin Potentiation of anti-coagulant effect Avoid or monitor INR closely Beta-blockers Corticisteroids Cyclosporine Digoxin Estrogen Fluconazole Opioid analgesics Quinidine Sulfonylureas Verapamil Decreased plasma levels of interacting drugs due to induction of multiple enzymes of Cytochrome P450 oxidase system Avoid or monitor closely for decreased clinical efficacy of interacting drug 74 ANTIMICROBIAL USE IN PREGNANCY Pregnancy Risk Category X D C B A Description * Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant. There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a lifethreatening situation or for a serious disease for which safer drugs cannot be used or are ineffective). Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus. Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters). Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm appears remote. * The descriptions for the risk categories are those used by the Food and Drug Administration. Federal Register 1980;44:37434-67. 75 ANTIMICROBIAL USE IN PREGNANCY Consultation with Obstetrics or Infectious Disease may be considered Antimicrobials generally considered to be safe in pregnancy Risk Category Amphotericin B .................................................................... B Azithromycin ........................................................................ B Aztreonam ........................................................................... B Cephalosporins.................................................................... B Clindamycin ......................................................................... B Erythromycin........................................................................ B Famciclovir........................................................................... B Metronidazole ...................................................................... B Nitrofurantoin 1 ..................................................................... B Penicillins............................................................................. B Valacyclovir.......................................................................... B Antimicrobials to be used with caution in pregnancy Acyclovir .............................................................................. C Aminoglycosides.................................................................. D Clarithromycin...................................................................... C Ganciclovir ........................................................................... C Fluconazole ......................................................................... C Imipenem-cilastatin.............................................................. C Indinavir ............................................................................... C Ketoconazole ....................................................................... C Lamivudine .......................................................................... C Nelfinavir.............................................................................. B Nevirapine............................................................................ C Nystatin................................................................................ C Rifampin............................................................................... C Ritonavir............................................................................... B Sulfonamides 1,2 ................................................................... B Stavudine............................................................................. C Sulfamethoxazole / trimethroprim 1,2 .................................... B Trimethoprim........................................................................ C Zalcitabine ........................................................................... C Vancomycin ......................................................................... C Zidovudine ........................................................................... C Antimicrobials which should be avoided in pregnancy Efavirenz.............................................................................. C Quinolones .......................................................................... C Ribavirin............................................................................... X Tetracyclines ....................................................................... D 1 Do not administer to pregnant patients with G-6-PD deficiency because of the risk of hemolysis to the mother and fetus 2 Risk factor D if administered near term 76
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