Antimicrobial Handbook 2013 Guidelines, Policies and Treatment Recommendations Content Developed by the Antimicrobial Subcommittee of the Pharmacy & Therapeutics Committee Published by authority of the Medical Advisory Committee Editor Bill Cornish, RPh, BScPhm, ACPR Drug Information Service Department of Pharmacy Associate Editor Sandra A.N. Walker, RPh, BSc, BScPhm, ACPR, PharmD., FCSHP Clinical Coordinator - Infectious Diseases and Antimicrobial Stewardship, Department of Pharmacy Associate Professor (Status), Leslie Dan Faculty of Pharmacy, University of Toronto July 2013 Sunnybrook Health Sciences Centre University of Toronto Toronto, Ontario Sunnybrook Antimicrobial Handbook 2013 i Acknowledgements Development and publication of this handbook was undertaken by the Antimicrobial Subcommittee of the Pharmacy & Therapeutics Committee. The Subcommittee comprises representatives of the Division of Infectious Diseases and the Departments of Microbiology and Pharmacy. Its members include the following individuals: Dr. V. Allen Department of Microbiology and Division of Infectious Diseases W. Cornish Secretary; Pharmacist, Drug Information Dr. N. Daneman Division of Infectious Diseases M. Elligsen Pharmacist, Antimicrobial Stewardship F. Gorenstein Pharmacy Manager, Holland Orthopaedic & Arthritic Centre Dr. S. Mubareka Department of Microbiology and Division of Infectious Diseases L. Palmay Pharmacist, Antimicrobial Stewardship Dr. A. Rachlis Division of Infectious Diseases Dr. A. Simor Chair; Head, Department of Microbiology and Division of Infectious Diseases Dr. S. Walker Pharmacist, Clinical Coordinator - Infectious Diseases and Antimicrobial Stewardship Desktop publishing by Media Source - Graphic Arts. This material has been prepared for use solely at the Sunnybrook Health Sciences Centre (SHSC). SHSC accepts no responsibility for use of this material by any person or institution not associated with the Hospital. © Departments of Microbiology and Pharmacy, Sunnybrook Health Sciences Centre. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical or otherwise, without permission of the editor. Sunnybrook Antimicrobial Handbook 2013 ii Foreword This Antimicrobial Handbook has been developed by the Antimicrobial Subcommittee of the Pharmacy and Therapeutics Committee, and is intended for use by Attending Physicians, House Staff, Pharmacists and other health care providers at Sunnybrook Health Sciences Centre. It includes practical information about commonly used anti-infective agents and provides suggested guidelines for the management of a variety of infectious diseases. We hope that it addresses frequently asked questions about antimicrobial therapy and serves as a useful aid for the management of hospitalized patients with infections. Your comments regarding the usefulness of this handbook are welcome. Please forward any comments or suggestions to Bill Cornish, Drug Information, Department of Pharmacy, Room EG 03; ext. 4513. E-mail: [email protected] Dr. A. Simor Head, Department of Microbiology and Division of Infectious Diseases Chair, Antimicrobial Subcommittee July 2013 Sunnybrook Antimicrobial Handbook 2013 iii TABLE OF CONTENTS Page SUBJECT i Title Page ii Acknowledgements iii Foreword iv Table of Contents Microbiology Profiles of Selected Common Pathogens 1 Staphylococcus aureus 2 Streptococcus pneumoniae 2 Enterococcus spp. 3 Pseudomonas aeruginosa 4 Blood Culture Isolates 5 Susceptibility of Blood Culture Isolates, SHSC 6 Susceptibility of Bacterial Isolates, SHSC 7 Susceptibility of Bacterial Isolates, ICUs 8 Antimicrobial Stewardship Policies for Use of Anti-infective Agents 9 Prescribing Restrictions 10 Automatic Substitution Policies 12 Intravenous to Oral Conversion (Step-down Therapy) Treatment Guidelines 14 Clostridium difficile Colitis 15 Febrile Neutropenia 17 Meningitis, Bacterial, Community-acquired 18 Pneumonia, Community-acquired 19 Pneumonia, Hospital-acquired 20 Skin and Skin Structure Infections 21 Urinary Tract Infections, Uncomplicated Sunnybrook Antimicrobial Handbook 2013 iv Drug Use Guidelines 22 Acyclovir and Valacyclovir 24 Aminoglycosides 33 Amphotericin B 35 Ampicillin and Amoxicillin 36 Azithromycin 37 Cefazolin 39 Ceftazidime 40 Ceftriaxone 41 Ciprofloxacin 43 Clindamycin 44 Cloxacillin 45 Co-trimoxazole (TMP/SMX) 50 Fluconazole 51 Levofloxacin 52 Meropenem 54 Metronidazole 55 Penicillin 57 Piperacillin-tazobactam 58 Vancomycin Miscellaneous Guidelines 62 Endocarditis Prophylaxis 66 HIV Post-Exposure Prophylaxis 67 Immunization for Asplenic Patients 69 Penicillin Allergy – Recommendations for use of Beta-Lactams 73 Pregnancy and Breastfeeding – Safe Use of Anti-infective Agents 91 Renal Insufficiency & Dialysis – Drug Dosing Recommendations 105 Surgical Antibiotic Prophylaxis Formulary Anti-infective Agents 122 Systemic Products 131 Ophthalmic / Otic Products 132 Topical / Vaginal Products 134 Cost Comparison for IV and Oral Anti-infective Agents 136 INDEX Sunnybrook Antimicrobial Handbook 2013 v PROFILES OF SELECTED COMMON PATHOGENS Staphylococcus aureus • Penicillin-sensitive S. aureus (incidence < 10%) - Drug of choice is penicillin • Penicillin-resistant S. aureus (incidence 90%) - Drugs of choice include cloxacillin, cefazolin, cephalexin • Methicillin-resistant S. aureus (MRSA) - Incidence < 5% in non-bacteremic, clinically stable patients; 20% in bacteremic patients, including patients who are systemically ill - Resistant to all penicillins, cephalosporins, and carbapenems - Treatment of choice for infection is vancomycin MRSA Colonization & Eradication Patient Selection: - The decision to attempt eradication of MRSA in colonized patients must be individualized - Not all patients are likely to benefit from decolonization, and some may experience adverse reactions - Judicious use of antibiotics, including mupirocin cream, is required in order to avoid development of further MRSA resistance - Infection Prevention & Control can be consulted to assist with decisions regarding management of colonized patients - Eradication is generally not recommended for patients with:  active infection  treatment with antibiotics  chronic skin lesions or ulcers  indwelling urinary catheter or other medical device Eradication Regimen: - If a decision is made to attempt to eradicate MRSA, the following regimen is recommended:  Chlorhexidine 2% washes once daily x 7 days  Rifampin 300 mg PO BID x 7 days  Doxycycline 100 mg BID OR Co-trimoxazole DS 1 PO BID x 7 days  Mupirocin 2% cream applied to the anterior nares TID x 7 days Don gloves and place 1 cm (1/2 inch) on the tip of a sterile cotton-tipped applicator and apply in one nostril. Using another sterile applicator, repeat the procedure in other nostril. Nostrils should then be pinched together and released repeatedly for about one minute to ensure even application of cream. Follow-up Monitoring: - Follow-up monitoring consists of repeat cultures obtained 7 days following the last day of administration of any of the above oral or topical treatments. Sunnybrook Antimicrobial Handbook 2013 1 Streptococcus pneumoniae • Penicillin-sensitive S. pneumoniae (≥ 85%): - drug of choice is penicillin • Penicillin-resistant S. pneumoniae - incidence in Canada (2008) is approximately 16% - initial treatment for meningitis due to these organisms is a combination of ceftriaxone plus vancomycin (see page 17) (vancomycin can be discontinued following confirmation that the organism is sensitive to ceftriaxone) Enterococcus spp. A. Susceptibility • Enterococci are intrinsically and predictably resistant to: - cephalosporins, cloxacillin, clindamycin, co-trimoxazole (TMP-SMX), aminoglycosides • Agents with activity against Enterococcus include ampicillin, piperacillin-tazobactam, vancomycin (nitrofurantoin for UTI only) • Vancomycin-resistant enterococci (VRE): - acquired resistance to vancomycin is increasing - this may be transferable to S. aureus - frequency of VRE increases with increased use of vancomycin (see vancomycin section, page 58, for guidelines on appropriate use) B. Treatment 1) Urinary Tract Infection Treatment: ampicillin 1-2g IV Q6H, or amoxicillin 500 mg po TID Alternatives: vancomycin 1g Q12H, or nitrofurantoin 50-100 mg po QID 2) Bacteremia (without endocarditis) Patients with enterococcal bacteremia should be assessed for possible endocarditis. If present, treat as recommended in Section 3. Treatment: ampicillin 2g IV Q6H ± gentamicin 1mg/kg IV Q8H* Alternative: vancomycin 1g IV Q12H ± gentamicin 1mg/kg IV Q8H* 3) Endocarditis Treatment: ampicillin 2g IV Q4H plus gentamicin 1mg/kg IV Q8H* Alternative: vancomycin 1g IV Q8H plus gentamicin 1mg/kg IV Q8H* * Low-dose gentamicin is appropriate when used for synergistic effect during combination therapy. Once-daily, high-dose regimens against gram positive cocci such as enterococci are not recommended for synergy. (see page 29, section 2). Sunnybrook Antimicrobial Handbook 2013 2 Pseudomonas aeruginosa A. Resistance P. aeruginosa is intrinsically and predictably resistant to: • penicillin/ampicillin • first/second generation cephalosporins • ceftriaxone, cefotaxime • erythromycin • clindamycin • vancomycin • co-trimoxazole (TMP/SMX) B. Susceptibility Antimicrobial agents that may be active against P. aeruginosa and may be used to treat infection due to this organism include: • aminoglycosides (tobramycin, amikacin) • piperacillin/tazobactam • ceftazidime • meropenem • ciprofloxacin (incidence of resistance is 30 - 40%) Note: prescribing of meropenem and IV ciprofloxacin is restricted (see details, page 9) C. Treatment 1) For uncomplicated P. aeruginosa infections of the urinary tract or skin and skin structure, antimicrobial therapy with a single agent may be used, such as: • ciprofloxacin 750 mg po Q12H • ceftazidime 2 g IV Q8H • tobramycin 7 mg/kg IV Q24H 2) For P. aeruginosa pneumonia or bacteremia or complicated infections, treatment with a combination of antibiotics is generally recommended. Example regimens include: • piperacillin-tazobactam 4.5 g IV Q6H plus tobramycin 7 mg/kg IV Q24H or • ceftazidime 2 g IV Q8H plus tobramycin 7 mg/kg IV Q24H Sunnybrook Antimicrobial Handbook 2013 3 Sunnybrook Health Sciences Centre Blood Culture Isolates SUNNYBROOK HEALTH SCIENCES CENTRE BLOOD CULTURE ISOLATES 2012 25% Coagulase negative 20% Others Staphylococci Su n n yb roo 2% Yeast k A ntim 3% 4icro Anaerobes b ial H an d bo ok 2 13% 0 Staphylococcus aureus 1 3 27% Coliforms 6% Enterococci 4% Pseudomonas aeruginosa ANTIMICROBIAL SUSCEPTIBILITY OF BLOOD CULTURE BACTERIAL ISOLATES IN ENTIRE HOSPITAL (% SUSCEPTIBLE) Sun GORRAGMAN PISOMSIST IVE n yb PEN CLOX CEF VAN # of ro isolates o k A S. aureus 0* 87 87 100 109 5ntimicro CGoRaAgM n eNgE sGtaApThI VE 0 * 13 13 10 0 52 b ial H ORGANISMS AMP CEF CFX GEN TOB SXT CIP TAZ PIP/TAZO MERO # of an isolates d bo E.coli 50 84 86 86 85 70 72 86 90 99 182 ok 2 Klebsiella spp 0 85 90 98 92 90 86 90 91 100 87 01 Enterobacter spp. 0 0 62 98 95 98 93 62 73 100 40 3 Other Coliforms 28 28 100 90 90 93 92 100 96 100 39 P. aeruginosa 0 0 0 90 90 0 70 74 76 77 42 AMP=ampicillin; CEF=cefazolin; CFX=ceftriaxone, CIP=ciprofloxacin ,CLIN=clindamycin; CLOX=cloxacillin; ERY=erythromycin; GEN=gentamicin; MERO=meropenem; PEN=penicillin; PIP/TAZO=piperacillin/tazobactam; SXT=co-trimoxazole; TOB=tobramycin; TAZ=ceftazidime; VAN=vancomycin * routinely reported as resistant