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Manual clsi 2005

  1. 1. M100-S15 Vol. 25 No. 1 Replaces M100-S14January 2005 Vol. 24 No. 1Performance Standards for AntimicrobialSusceptibility Testing; FifteenthInformational Supplement This document provides updated tables for the Clinical and Laboratory Standards Institute (CLSI)/NCCLS antimicrobial susceptibility testing standards M2-A8 and M7-A6. An informational supplement for global application developed through the Clinical and Laboratory Standards Institute consensus process.
  2. 2. Clinical and Laboratory Standards InstituteProviding NCCLS standards and guidelines, ISO/TC 212 standards, and ISO/TC 76 standardsThe Clinical and Laboratory Standards Institute (CLSI) Most documents are subject to two levels of(formerly NCCLS) is an international, interdisciplinary, consensus–“proposed” and “approved.” Depending onnonprofit, standards-developing, and educational the need for field evaluation or data collection,organization that promotes the development and use of documents may also be made available for review at anvoluntary consensus standards and guidelines within the intermediate consensus level.healthcare community. It is recognized worldwide for the Proposed A consensus document undergoes the firstapplication of its unique consensus process in the stage of review by the healthcare community as adevelopment of standards and guidelines for patient proposed standard or guideline. The document shouldtesting and related healthcare issues. Our process is based receive a wide and thorough technical review, includingon the principle that consensus is an effective and cost- an overall review of its scope, approach, and utility, and aeffective way to improve patient testing and healthcare line-by-line review of its technical and editorial content.services. Approved An approved standard or guideline hasIn addition to developing and promoting the use of achieved consensus within the healthcare community. Itvoluntary consensus standards and guidelines, we provide should be reviewed to assess the utility of the finalan open and unbiased forum to address critical issues document, to ensure attainment of consensus (i.e., thataffecting the quality of patient testing and health care. comments on earlier versions have been satisfactorilyPUBLICATIONS addressed), and to identify the need for additional consensus documents.A document is published as a standard, guideline, orcommittee report. Our standards and guidelines represent a consensus opinion on good practices and reflect the substantialStandard A document developed through the consensus agreement by materially affected, competent, andprocess that clearly identifies specific, essential interested parties obtained by following CLSI’srequirements for materials, methods, or practices for use established consensus procedures. Provisions in CLSIin an unmodified form. A standard may, in addition, standards and guidelines may be more or less stringentcontain discretionary elements, which are clearly than applicable regulations. Consequently, conformanceidentified. to this voluntary consensus document does not relieve theGuideline A document developed through the consensus user of responsibility for compliance with applicableprocess describing criteria for a general operating regulations.practice, procedure, or material for voluntary use. A COMMENTSguideline may be used as written or modified by the userto fit specific needs. The comments of users are essential to the consensus process. Anyone may submit a comment, and allReport A document that has not been subjected to comments are addressed, according to the consensusconsensus review and is released by the Board of process, by the committee that wrote the document. AllDirectors. comments, including those that result in a change to theCONSENSUS PROCESS document when published at the next consensus level and those that do not result in a change, are responded to byThe CLSI voluntary consensus process is a protocol the committee in an appendix to the document. Readersestablishing formal criteria for: are strongly encouraged to comment in any form and at• the authorization of a project any time on any document. Address comments to Clinical and Laboratory Standards Institute, 940 West Valley• the development and open review of documents Road, Suite 1400, Wayne, PA 19087, USA. VOLUNTEER PARTICIPATION• the revision of documents in response to comments by users Healthcare professionals in all specialties are urged to volunteer for participation in CLSI projects. Please• the acceptance of a document as a consensus contact us at exoffice@clsi.org or +610.688.0100 for standard or guideline. additional information on committee participation.
  3. 3. Vol. 25 No. 1 M100-S15Performance Standards for Antimicrobial Susceptibility Testing;Fifteenth Informational SupplementAbstractThe supplemental information presented in this document is intended for use with the antimicrobialsusceptibility testing procedures published in the following Clinical and Laboratory Standards Institute(CLSI)/NCCLS approved standards: M2-A8—Performance Standards for Antimicrobial DiskSusceptibility Tests; Approved Standard—Eighth Edition; and M7-A6—Methods for DilutionAntimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Sixth Edition.The standards contain information about both disk (M2) and dilution (M7) test procedures for aerobicbacteria.Clinicians depend heavily on information from the clinical microbiology laboratory for treatment of theirseriously ill patients. The clinical importance of antimicrobial susceptibility test results requires that thesetests be done under optimal conditions and that laboratories have the capability to provide results for thenewest antimicrobial agents.The tabular information presented here represents the most current information for drug selection,interpretation, and quality control using the procedures standardized in M2 and M7. Users should replacethe tables published earlier with these new tables. (Changes in the tables since the most recent editionappear in boldface type.)Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial SusceptibilityTesting; Fifteenth Informational Supplement. CLSI document M100-S15 (ISBN 1-56238-556-9). Clinicaland Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898USA, 2005. The data in the interpretive tables in this supplement are valid only if the methodologies in M2-A8—Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard—Eighth Edition; and M7-A6—Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Sixth Edition are followed. 1
  4. 4. January 2005 M100-S152
  5. 5. M100-S15 ISBN 1-56238-556-9 ISSN 0273-3099Performance Standards for Antimicrobial Susceptibility Testing;Fifteenth Informational SupplementVolume 25 Number 1Matthew A. Wikler, M.D., M.B.A., FIDSAFranklin R. Cockerill, III, M.D.William A. Craig, M.D.Michael N. Dudley, Pharm.D.George M. Eliopoulos, M.D.David W. Hecht, M.D.Janet F. Hindler, MCLS, M.T.(ASCP)Donald E. Low, M.D.Daniel J. Sheehan, Ph.D.Fred C. Tenover, Ph.D., ABMMJohn D. Turnidge, M.D.Melvin P. Weinstein, M.D.Barbara L. Zimmer, Ph.D.Mary Jane Ferraro, Ph.D., M.P.H.Jana M. Swenson, M.M.Sc.
  6. 6. January 2005 M100-S15This publication is protected by copyright. No part of it may be reproduced, stored in a retrieval system,transmitted, or made available in any form or by any means (electronic, mechanical, photocopying,recording, or otherwise) without prior written permission from Clinical and Laboratory Standards Institute,except as stated below.Clinical and Laboratory Standards Institute hereby grants permission to reproduce limited portions of thispublication for use in laboratory procedure manuals at a single site, for interlibrary loan, or for use ineducational programs provided that multiple copies of such reproduction shall include the followingnotice, be distributed without charge, and, in no event, contain more than 20% of the document’s text. Reproduced with permission, from CLSI/NCCLS publication M100-S15—Performance Standards for Antimicrobial Susceptibility Testing; Fifteenth Informational Supplement (ISBN 1-56238-556-9). Copies of the current edition may be obtained from Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898, USA.Permission to reproduce or otherwise use the text of this document to an extent that exceeds theexemptions granted here or under the Copyright Law must be obtained from Clinical and LaboratoryStandards Institute by written request. To request such permission, address inquiries to the Executive VicePresident, Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne,Pennsylvania 19087-1898, USA.Copyright ©2005. Clinical and Laboratory Standards Institute.Suggested Citation(Clinical and Laboratory Standards Institute/NCCLS. Performance Standards for AntimicrobialSusceptibility Testing; Fifteenth Informational Supplement. CLSI/NCCLS document M100-S15 [ISBN 1-56238-556-9]. Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne,Pennsylvania 19087-1898 USA, 2005.)Fifteenth Informational Supplement Eleventh Informational SupplementJanuary 2005 January 2001Fourteenth Informational Supplement Tenth Informational SupplementJanuary 2004 January 2000Thirteenth Informational Supplement Ninth Informational SupplementJanuary 2003 January 1999Twelfth Informational Supplement Eighth Informational SupplementJanuary 2002 January 1998ISBN 1-56238-556-9ISSN 0273-30994
  7. 7. Vol. 25 No. 1 M100-S15Committee Membership Committee MembershipArea Committee on MicrobiologyMary Jane Ferraro, Ph.D., M.P.H. Thomas R. Shryock, Ph.D. Lynne S. Garcia, M.S.Chairholder Lilly Research Laboratories LSG & AssociatesMassachusetts General Hospital Greenfield, Indiana Santa Monica, CaliforniaBoston, Massachusetts Jana M. Swenson, M.M.Sc. Richard L. Hodinka, Ph.D.James H. Jorgensen, Ph.D. Centers for Disease Control and Children’s Hospital of PhiladelphiaVice-Chairholder Prevention Philadelphia, PennsylvaniaUniversity of Texas Health Science Atlanta, GeorgiaCenter Michael A. Pfaller, M.D. University of Iowa College of MedicineSan Antonio, Texas Michael L. Wilson, M.D. Iowa City, Iowa Denver Health Medical CenterDonald R. Callihan, Ph.D. Denver, Colorado Robert P. Rennie, Ph.D.BD Diagnostic Systems University of Alberta HospitalSparks, Maryland Advisors Edmonton, Alberta, Canada Melvin P. Weinstein, M.D.David L. Sewell, Ph.D. Ellen Jo Baron, Ph.D. Robert Wood Johnson Medical SchoolVeterans Affairs Medical Center Stanford Univ. Hospital & Medical New Brunswick, New JerseyPortland, Oregon School Stanford, California Gail L. Woods, M.D. ARUP Research Institute Salt Lake City, UtahSubcommittee on Antimicrobial Susceptibility TestingMatthew A. Wikler, M.D., M.B.A., Donald E. Low, M.D. John S. Bradley, M.D.FIDSA Mount Sinai Hospital Children’s Hospital and Health CenterChairholder Toronto, Ontario, Canada San Diego, CaliforniaPeninsula Pharmaceuticals, Inc.Alameda, California Daniel J. Sheehan, Ph.D. Steven D. Brown, Ph.D. Pfizer Inc. The Clinical Microbiology InstituteFranklin R. Cockerill, III, M.D. New York, New York Wilsonville, OregonMayo Clinic/Mayo FoundationRochester, Minnesota Fred C. Tenover, Ph.D., ABMM Karen Bush, Ph.D. Centers for Disease Control and Johnson & Johnson PharmaceuticalWilliam A. Craig, M.D. Prevention Research InstituteUniversity of Wisconsin Atlanta, Georgia Raritan, New JerseyMadison, Wisconsin John D. Turnidge, M.D. Robert K. Flamm, Ph.D.Michael N. Dudley, Pharm.D. Women’s and Children’s Hospital Focus Technologies, Inc.Diversa Corporation North Adelaide, Australia Herndon, VirginiaSan Diego, California Melvin P. Weinstein, M.D. Lawrence V. Friedrich, Pharm.D. Robert Wood Johnson Medical SchoolGeorge M. Eliopoulos, M.D. Cubist Pharmaceuticals New Brunswick, New JerseyBeth Israel Deaconess Medical Center Mt. Pleasant, South CarolinaBoston, Massachusetts Barbara L. Zimmer, Ph.D. Dade Behring MicroScan Dwight J. Hardy, Ph.D.David W. Hecht, M.D. West Sacramento, California University of Rochester MedicalLoyola University Medical Center CenterMaywood, Illinois Advisors Rochester, New YorkJanet F. Hindler, MCLS, M.T.(ASCP) Patricia A. Bradford, Ph.D.UCLA Medical Center Wyeth ResearchLos Angeles, California Pearl River, New York 5
  8. 8. January 2005 M100-S15 Advisors (Continued)Committee Membership Yoichi Hirakata, M.D., Ph.D. Charles H. Nightingale, Ph.D. George H. Talbot, M.D. Nagasaki University School of Hartford Hospital Talbot Advisors LLC Medicine and Dentistry Hartford, Connecticut Wayne, Pennsylvania Nagasaki, Japan John H. Powers, III, M.D., FACP Staff Ronald N. Jones, M.D. FDA Center for Drug Evaluation and Research Clinical and Laboratory Standards The JONES Group/JMI Institute North Liberty, Iowa Rockville, Maryland Wayne, Pennsylvania Gunnar Kahlmeter, M.D., Ph.D. L. Barth Reller, M.D. Tracy A. Dooley, M.L.T.(ASCP) ESCMID Duke University Medical Center Staff Liaison Sweden Durham, North Carolina Donna M. Wilhelm John E. McGowan, Jr., M.D. Robert P. Rennie, Ph.D. Editor Emory University, Rollins School of University of Alberta Hospital Public Health Edmonton, Alberta, Canada Melissa A. Lewis Atlanta, Georgia Assistant Editor Sally Selepak, M.T.(ASCP) Linda A. Miller, Ph.D. FDA Center for Devices and GlaxoSmithKline Radiological Health Collegeville, Pennsylvania Rockville, Maryland Susan D. Munro, M.T.(ASCP) Jana M. Swenson, M.M.Sc. Stanford University Hospital and Centers for Disease Control and Clinics Prevention Stanford, California Atlanta, Georgia 6
  9. 9. Vol. 25 No. 1 M100-S15ContentsAbstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Committee Membership. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Updated Information in This Edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11Subcommittee on Antimicrobial Susceptibility Testing Mission Statement . . . . . . . . . . . . . . . . . . . . 17M2-A8 Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard—Eighth Edition Table of ContentsIntroduction to Tables 1 through 1A and 2A through 2I for Use With M2-A8—Disk Diffusion. . . . 19Table 1. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Nonfastidious Organisms by Clinical MicrobiologyLaboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24Table 1A. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Fastidious Organisms by Clinical MicrobiologyLaboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30Tables 2A-2I. Zone Diameter Interpretive Standards and Equivalent Minimal InhibitoryConcentration (MIC) Breakpoints for:2A. Enterobacteriaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342B. Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia, and Burkholderiacepacia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402C. Staphylococcus spp.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442D. Enterococcus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 522E. Haemophilus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562F. Neisseria gonorrhoeae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 602G. Streptococcus pneumoniae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 642H. Streptococcus spp. Other Than Streptococcus pneumoniae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 662I. Vibrio cholerae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69Table 3. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of Disk DiffusionTesting of Nonfastidious Organisms (Using Mueller-Hinton Medium Without Blood or OtherSupplements) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 7
  10. 10. January 2005 M100-S15 Contents (Continued) Table 3A. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of Disk Diffusion Testing of Fastidious Organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Table 3B. Reference Guide to Quality Control Testing Frequency. . . . . . . . . . . . . . . . . . . . . . . . . . . 74 Table 4. Suggestions for Verification of Antimicrobial Susceptibility Test Results and Confirmation of Organism Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 Glossary I (Part 1). ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . . . . . . 78 Glossary I (Part 2). Non-ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . . 79Table of Contents Glossary II. Abbreviations/Routes of Administration/Drug Class for Antimicrobial Agents Listed in M100-S15. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 List of Identical Abbreviations Used for More Than One Antimicrobial Agent in U.S. Diagnostic Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Summary of Comments and Subcommittee Responses (M2-Disk Diffusion) . . . . . . . . . . . . . . . . . . 84 M7-A6 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Sixth Edition Introduction to Tables 1 Through 1B and 2A Through 2L for Use With M7-A6—MIC Testing. . . . 87 Table 1. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should Be Considered for Routine Testing and Reporting on Nonfastidious Organisms by Clinical Microbiology Laboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 Table 1A. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should Be Considered for Routine Testing and Reporting on Fastidious Organisms by Clinical Microbiology Laboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 Table 1B. Suggested Grouping of Antimicrobial Agents That Should Be Considered for Testing and Reporting on Potential Agents of Bioterrorism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 Tables 2A-2L. MIC Interpretive Standards (µg/mL) for: 2A. Enterobacteriaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 2B. Pseudomonas aeruginosa and Other Non-Enterobacteriaceae . . . . . . . . . . . . . . . . . . . . . . . . . 108 2C. Staphylococcus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 2D. Enterococcus spp.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 2E. Haemophilus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 2F. Neisseria gonorrhoeae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 2G. Streptococcus pneumoniae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 2H. Streptococcus spp. Other Than Streptococcus pneumoniae. . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 2I. Vibrio cholerae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 8
  11. 11. Vol. 25 No. 1 M100-S15Contents (Continued)2J. Helicobacter pylori . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1352K. Bacillus anthracis, Yersinia pestis, Burkholderia mallei, Burkholderia pseudomallei, andFrancisella tularensis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1362L. Neisseria meningitidis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138Table 3. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µg/mL) of Nonfastidious Organisms (Using Cation-AdjustedMueller-Hinton Medium Without Blood or Other Nutritional Supplements) . . . . . . . . . . . . . . . . . . 140Table 3A. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µg/mL) of Fastidious Organisms. . . . . . . . . . . . . . . . . . . . . . . . 142 Table of ContentsTable 3B. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µg/mL) Generated in Cation-Adjusted Mueller-Hinton Broth+ 2% Defined Growth Supplement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144Table 3C. Reference Guide to Quality Control Testing Frequency. . . . . . . . . . . . . . . . . . . . . . . . . . 145Table 4. Solvents and Diluents for Preparation of Stock Solutions of Antimicrobial Agents . . . . . 146Table 5. Scheme for Preparing Dilutions of Antimicrobial Agents to Be Used in Agar DilutionSusceptibility Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149Table 6. Scheme for Preparing Dilutions of Antimicrobial Agents to Be Used in Broth DilutionSusceptibility Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150Table 7. Suggested Modifications of Standard Methods for Susceptibility Testing ofListeria spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151Table 8. Suggestions for Verification of Antimicrobial Susceptibility Test Results andConfirmation of Organism Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152Glossary I (Part 1). ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . . . . 154Glossary I (Part 2). Non-ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . 155Glossary II. Abbreviations/Routes of Administration/Drug Class for Antimicrobial Agents Listedin M100-S15. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156List of Identical Abbreviations Used for More Than One Antimicrobial Agent in U.S. DiagnosticProducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159Summary of Comments and Subcommittee Responses (M7-MIC Testing) . . . . . . . . . . . . . . . . . . . 160Related CLSI/NCCLS Publications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 9
  12. 12. January 2005 M100-S15The Clinical and Laboratory Standards Institute consensus process, which is the mechanism for movinga document through two or more levels of review by the healthcare community, is an ongoing process.Users should expect revised editions of any given document. Because rapid changes in technology mayaffect the procedures, methods, and protocols in a standard or guideline, users should replace outdatededitions with the current editions of CLSI/NCCLS documents. Current editions are listed in the CLSIcatalog, which is distributed to member organizations, and to nonmembers on request. If yourorganization is not a member and would like to become one, and to request a copy of the catalog, contactus at: Telephone: +610.688.0100; Fax: +610.688.0700; E-Mail: exoffice@clsi.org; Website:www.clsi.org.10
  13. 13. Vol. 25 No. 1 M100-S15Updated Information in This EditionThis document includes all of the tables from the Clinical and Laboratory Standards Institute DiskDiffusion (M2) susceptibility testing and Aerobic Dilution (M7) susceptibility testing documents. Thereare several important changes to the tables that have resulted from meetings of the Subcommittee onAntimicrobial Susceptibility Testing during 2004. Included below is a summary of the changes in thisdocument, which supersede the tables published in 2004 and in earlier years.Summary of Major Changes in This DocumentThe list includes the “major” changes in this document. Other minor or editorial changes have been madeto the general formatting and to some of the table footnotes. Boldface type is used to highlight the changesin each table.Additions/Changes/DeletionsThe following are additions or changes unless otherwise noted as a “deletion.”Clarification of temperature range for incubation in “Testing Conditions” box (M2 and M7; Tables 2A-2K)Enterobacteriaceae:ESBL Testing (M2 and M7; Table 2A) Recommendations for testing Proteus mirabilis for ESBL production with slight modification of Summary of Changes several screening test breakpoints Escherichia coli ATCC® 25922 for QC of ESBL phenotypic confirmatory test (M7 only) Clarification of QC frequency for ESBL screening and confirmatory testsNon-Enterobacteriaceae:Separate lists of antimicrobial agents suggested for testing and reporting for Pseudomonas aeruginosa,Acinetobacter spp., Burkholderia cepacia, and Stenotrophomonas maltophilia (M2 and M7; Table 1).Footnotes j (M2 and M7) and k (M7) were modified accordingly.Qualification of suggestion that cefotaxime, ceftriaxone, and ceftizoxime be considered for reporting onlyon Pseudomonas spp. (not P. aeruginosa) and other nonfastidious, glucose-nonfermenting, gram-negativebacilli (Test/Report Group C) (M7; Table 1)Polymyxin BMIC interpretive criteria which can be used to predict results for colistin also (M7; Table 2B)Trimethoprim-sulfamethoxazoleDisk diffusion interpretive criteria for B. cepacia (M2; Table 2B)Staphylococcus spp.:Clindamycin induction testSuggestions for quality assessment and quality control (M2 and M7; Table 2C and “Minimal QCRecommendations” box)DaptomycinTest/Report Group B (M2 and M7; Table 1) 11
  14. 14. January 2005 M100-S15 Updated Information in This Edition (Continued) Daptomycin (Continued) Disk diffusion and MIC interpretive criteria (M2 and M7; Table 2C) Special broth and agar media recommendations for testing daptomycin (M7; Table 2C and “Testing Conditions” box) Flucloxacillin - results can be deducted from testing oxacillin (M7; Table 2C) Gatifloxacin - revised interpretive criteria (M2 and M7; Table 2C) Levofloxacin - revised interpretive criteria (M2 and M7; Table 2C) Moxifloxacin Test/Report Group C (M2 and M7; Table 1) Disk diffusion and MIC interpretive criteria (M2 and M7; Table 2C) Ofloxacin - revised interpretive criteria (M2 and M7; Table 2C) Telithromycin Test/Report Group B (M2 and M7; Table 1) Revised Test/Report Group (M2 and M7; Table 2C)Summary of Changes Vancomycin Suggestion for detecting S. aureus strains with reduced susceptibility to vancomycin with reference to BHI vancomycin agar screen test (M2 and M7; Table 2C) Oxacillin related issues/comments (M2 and M7; Table 2C) Clarification of recommendations for reporting beta-lactam results on oxacillin-susceptible staphylococci (M2 and M7; Table 2C) Expanded discussion on use of mecA and PBP 2a tests Expanded discussion on use of cefoxitin disk test Staphylococcus lugdunensis - cefoxitin (disk diffusion) and oxacillin (disk diffusion and MIC) interpretive criteria for S. aureus should be used for S. lugdunensis Enterococcus spp.: Daptomycin Test/Report Group B for vancomycin-susceptible Enterococcus faecalis only (M2 and M7; Table 1) Disk diffusion and MIC interpretive criteria (M2 and M7; Table 2D) Special broth and agar media recommendations for testing daptomycin (M7; Table 2D “Testing Conditions” box) Haemophilus spp.: Telithromycin Test/Report Group C (M2 and M7; Table 1A) Revised Test/Report Group (M2 and M7; Table 2E) 12
  15. 15. Vol. 25 No. 1 M100-S15Updated Information in This Edition (Continued)Streptococcus pneumoniae:FluoroquinolonesDeleted “or” designation and eliminated the ability to use results from testing one fluoroquinolone topredict results for another fluoroquinolone (M2 and M7; Group B, Table 1A and Table 2G)TelithromycinTest/Report Group B (M2 and M7; Table 1A)Revised Test/Report Group (M2 and M7; Table 2G)Streptococcus spp. Other Than Streptococcus pneumoniaeClindamycinRecommendation for detecting inducible clindamycin resistance in beta-hemolytic streptococci (M2 andM7; Table 2H)Clindamycin and ErythromycinRecommendation for testing Group B streptococci for intrapartum prophylaxis (M2 and M7; Table 2H)DaptomycinTest/Report Group C (M2 and M7; Table 1A) Summary of ChangesDisk diffusion and MIC interpretive criteria for beta-hemolytic streptococci only (M2 and M7; Table 2H)Special broth and agar media recommendations for testing daptomycin (M7; Table 2H “TestingConditions” box)Potential Agents of Bioterrorism:MIC Table expanded to include recommendations and interpretive criteria for Francisella tularensis(M7; Table 2K)Neisseria meningitidis:MIC interpretive standards listed in new table (M7; Table 2L)QC Range Changes/Additions (Table 3):Chloramphenicol - Staphylococcus aureus ATCC® 29213 (M7)Colistin - Escherichia coli ATCC® 25922 (M2 and M7) Pseudomonas aeruginosa ATCC® 27853 (M2 and M7)Dalbavancin - Staphylococcus aureus ATCC® 29213 (M7) Enterococcus faecalis ATCC® 29212 (M7)Daptomycin - Enterococcus faecalis ATCC® 29212 (M7) 13
  16. 16. January 2005 M100-S15 Updated Information in This Edition (Continued) Doripenem - Staphylococcus aureus ATCC® 25923 (M2) Staphylococcus aureus ATCC® 29213 (M7) Escherichia coli ATCC® 25922 (M2 and M7) Enterococcus faecalis ATCC® 29212 (M7) Pseudomonas aeruginosa ATCC® 27853 (M2 and M7) Doxycycline - Staphylococcus aureus ATCC® 29213 (M7) Enterococcus faecalis ATCC® 29212 (M7) Polymyxin B - Escherichia coli ATCC® 25922 (M2 and M7) Pseudomonas aeruginosa ATCC® 27853 (M2 and M7) Telavancin - Staphylococcus aureus ATCC® 25923 (M2) Staphylococcus aureus ATCC® 29213 (M7) Enterococcus faecalis ATCC® 29212 (M7) Tigecycline - Staphylococcus aureus ATCC® 25923 (M2) Staphylococcus aureus ATCC® 29213 (M7) Escherichia coli ATCC® 25922 (M2 and M7)Summary of Changes Pseudomonas aeruginosa ATCC® 27853 (M2) Enterococcus faecalis ATCC® 29212 added (M7) Tigecycline - instructions for using fresh CAMHB for broth microdilution tests QC Range Changes/Additions (Table 3A): Dalbavancin - Streptococcus pneumoniae ATCC® 49619 (M7) Doripenem - Streptococcus pneumoniae ATCC® 49619 (M2 and M7) Haemophilus influenzae ATCC® 49247 (M2 and M7) Doxycycline - Streptococcus pneumoniae ATCC® 49619 (M7) Telavancin - Streptococcus pneumoniae ATCC® 49619 (M2 and M7) Tigecycline - Haemophilus influenzae ATCC® 49247 (M2 and M7) Neisseria gonorrhoeae ATCC® 49226 (M2) Streptococcus pneumoniae ATCC® 49619 (M2 and M7) QC Ranges for MICs Generated in Cation-Adjusted MHB with Growth Supplement (M7; new Table 3B) Reference Guide to QC Testing Frequency (M2, Table 3B; M7, Table 3C) Clarification that recommendations in this table do not eliminate the need for routine weekly or daily QC testing (M2, Table 3B; M7, Table 3C) 14
  17. 17. Vol. 25 No. 1 M100-S15Updated Information in This Edition (Continued)Indication that users of FDA-cleared antimicrobial susceptibility test systems should utilize QC limitslisted in the product literature (M7; Table 3C)Suggestions for Verification of Antimicrobial Susceptibility Test Results and Confirmation ofOrganism Identification (MIC) (M2, Table 4; M7, Table 8)Daptomycin-NS under Category I for the following organisms: Enterococcus spp.; Enterococcus faecalis;Enterococcus faecium; Staphylococcus aureus; Staphylococcus, coagulase-negative; Streptococcus, betagroup; and Streptococcus, viridans group (M2, Table 4; M7, Table 8)Suggestion that laboratories report to their public health department Salmonella spp. found to beintermediate or resistant 3rd-generation cephalosporins and/or intermediate or resistant tofluoroquinolones or resistant to nalidixic acid. (M2, Table 4; M7, Table 8)Suggested Modifications of Standard Methods for Susceptibility Testing:Deletion:Recommendations for Neisseria meningitidis as standard recommendations of this species are now inTable 2L (M7, Table 7)Solvents and Diluents for Preparation of Stock Solutions of Antimicrobial Agents Summary of ChangesColistin, Dalbavancin, Daptomycin, Doripenem, Polymyxin B, Telavancin, and Tigecycline(M2, Table 4)Glossaries I and IIColistin, Dalbavancin, Doripenem, Oritavancin, Polymyxin B, Telavancin, and Tigecycline added(Glossaries I and II) It is important for users of M2-A8 and M7-A6 to recognize that commercial susceptibility testing devices are not addressed in these standards. The methods described herein are generic reference procedures that can be used for routine susceptibility testing by clinical laboratories, or that can be used by clinical laboratories to evaluate commercial devices for possible routine use. Results generated by the CLSI/NCCLS reference methods are used by the United States Food and Drug Administration to evaluate the performance of commercial systems before clearance is given for marketing in the United States. Clearance by the FDA indicates that the agency concludes that commercial devices provide susceptibility results that are substantially equivalent to results generated using the CLSI/NCCLS reference methods for the organisms and antimicrobial agents described in the manufacturer’s approved package insert. Some laboratories could find that a commercial dilution, antibiotic gradient, colorimetric, turbidimetric, fluorometric, or other method is suitable for selective or routine use. 15
  18. 18. January 2005 M100-S1516
  19. 19. Vol. 25 No. 1 M100-S15Subcommittee on Antimicrobial Susceptibility Testing Mission StatementThe Subcommittee on Antimicrobial Susceptibility Testing is composed of representatives from theprofessions, government, and industry, including microbiology laboratories, government agencies,healthcare providers and educators, and pharmaceutical and diagnostic microbiology industries. Usingthe CLSI voluntary consensus process, the subcommittee develops standards that promote accurateantimicrobial susceptibility testing and appropriate reporting.The mission of the Subcommittee on Antimicrobial Susceptibility Testing is to:• Develop standard reference methods for antimicrobial susceptibility tests.• Provide quality control parameters for standard test methods.• Establish interpretive criteria for the results of standard antimicrobial susceptibility tests.• Provide suggestions for testing and reporting strategies that are clinically relevant and cost- effective.• Continually refine standards and optimize the detection of emerging resistance mechanisms through the development of new or revised methods, interpretive criteria, and quality control parameters.• Educate users through multimedia communication of standards and guidelines.• Foster a dialogue with users of these methods and those who apply them.The ultimate purpose of the subcommittee’s mission is to provide useful information to enablelaboratories to assist the clinician in the selection of appropriate antimicrobial therapy for patient care.The standards and guidelines are meant to be comprehensive and to include all antimicrobial agents forwhich the data meet established CLSI/NCCLS guidelines. The values that guide this mission are quality,accuracy, fairness, timeliness, teamwork, consensus, and trust. 17
  20. 20. January 2005 M100-S1518
  21. 21. For Use With M2-A8–Disk Diffusion M100-S15Introduction to Tables 1 Through 1A and 2A Through 2I for Use With M2-A8—Disk Diffusion On the following pages, you will find: 1. Tables 1 and 1A—Suggested groupings of U.S. FDA-approved antimicrobial agents that should be considered for routine testing and reporting by clinical microbiology laboratories. 2. For each organism group, an additional table (Tables 2A through 2I) that contains: a. Recommended testing conditions. b. Minimal QC recommendations. (See also the M2-A8 text document, Section 10.) c. General comments for testing the organism group and specific comments for testing particular drug/organism combinations. d. Suggested agents that should be considered for routine testing and reporting by clinical microbiology laboratories as specified in Tables 1 and 1A (test/report groups A, B, C, U; the latter for “urine”). e. Additional drugs that have an approved indication for the respective organism group, but would generally not warrant routine testing by a clinical microbiology laboratory in the United States (test/report group O for “other”; test/report group Inv. for “investigational” [not yet FDA approved]). f. Zone diameter interpretive criteria and equivalent MIC values which represent MIC breakpoints used in determining approximate zone diameter interpretive criteria. They relate to MICs determined by M7 methodology. Occasional discrepancies may exist between M2 and M7 due to methodological limitations.I. Selecting Antimicrobial Agents for Testing and ReportingA. Selection of the most appropriate antimicrobial agents to test and to report is a decision best made by each clinical laboratory in consultation with the infectious disease practitioners and the pharmacy, as well as the pharmacy and therapeutics and infection control committees of the medical staff. The recommendations here for each organism group comprise agents of proven efficacy that show acceptable in vitro test performance. Considerations in the assignment of agents to specific test/report groups include clinical efficacy, prevalence of resistance, minimizing emergence of resistance, cost, FDA indications, and current consensus recommendations for first- choice and alternative drugs, in addition to the specific issues described. Tests of selected agents may be useful for infection control purposes.B. The listing of drugs together in a single box designates clusters of comparable agents that need not be duplicated in testing, because interpretive results are usually similar and clinical efficacy comparable. In addition, an “or” designates a related group of agents that has an almost identical spectrum of activity and interpretive results, and for which cross-resistance and susceptibility are nearly complete. Therefore, usually only one of the agents within each selection box (cluster or related group) need be selected for testing. Agents reported must be tested, unless reporting based on testing another agent provides a more accurate result (e.g., susceptibility of staphylococci to cefazolin or cephalothin based on oxacillin testing), and they usually should match those included in the hospital formulary; or else the report should include footnotes indicating the agents that usually show comparable interpretive results. Unexpected results should be considered for reporting (e.g., resistance of Enterobacteriaceae to third-generation cephalosporins or imipenem).© Clinical and Laboratory Standards Institute. All rights reserved. 19
  22. 22. January 2005 Vol. 25 No. 1C. Test/Report Groups 1. As listed in Tables 1 and 1A, agents in Group A are considered appropriate for inclusion in a routine, primary testing panel, as well as for routine reporting of results for the specific organism groups. 2. Group B comprises agents that are important clinically, particularly for nosocomial infections, and they may warrant primary testing. However, they may be reported only selectively, such as when the organism is resistant to agents of the same class, as in Group A. Other indications for reporting the result might include a selected specimen source (e.g., a third-generation cephalosporin for enteric bacilli from cerebrospinal fluid [CSF] or trimethoprim-sulfamethoxazole for urinary tract isolates); a polymicrobial infection; infections involving multiple sites; on request in case of allergy, intolerance, or failure to respond to an agent in Group A; or for reporting to infection control as an epidemiologic aid. 3. Group C comprises alternative or supplemental antimicrobial agents that may require testing in those institutions that harbor endemic or epidemic strains resistant to several of the primary drugs (especially in the same class, e.g., β-lactams or aminoglycosides); for treatment of patients allergic to primary drugs; for treatment of unusual organisms (e.g., chloramphenicol for extraintestinal isolates of Salmonella spp. or some vancomycin- resistant enterococci); or for reporting to infection control as an epidemiologic aid. 4. Group U (“urine”) lists certain antimicrobial agents (e.g., nitrofurantoin and certain quinolones) that are used only or primarily for treating urinary tract infections. These agents should not be routinely reported against pathogens recovered from other sites of infection. Other agents with broader indications may be included in Group U for specific urinary pathogens (e.g., P. aeruginosa). 5. Group O (“other”) includes agents that have a clinical indication for the organism group but are generally not candidates for routine testing and reporting in the United States. 6. Group Inv. (“investigational”) includes agents that are investigational for the organism group and have not yet been approved by the FDA.D. Selective Reporting Each laboratory should decide which agents in the tables to report routinely (Group A) and which might be reported only selectively (from Group B), in consultation with the infectious disease practitioners and the pharmacy, as well as the pharmacy and therapeutics and infection control committees of the medical staff of the hospital. Selective reporting should help improve the clinical relevance of test reports and help minimize the selection of multiresistant nosocomial strains by overuse of broad-spectrum agents. Results for Group B agents not reported routinely should be available on request, or they may be reported for selected specimens. Unexpected resistance, when confirmed, should be reported (e.g., resistance to a secondary agent but susceptibility to a primary agent).20 © Clinical and Laboratory Standards Institute. All rights reserved.
  23. 23. For Use With M2-A8–Disk Diffusion M100-S15II. Reporting Results Recommended interpretive criteria are based on usual dosage regimens and routes of administration in the U.S.A. Susceptible, intermediate, or resistant interpretations of zone diameter measurements are reported and defined as follows: 1. Susceptible (S) The “susceptible” category implies that an infection due to the strain may be appropriately treated with the dosage of antimicrobial agent recommended for that type of infection and infecting species, unless otherwise contraindicated. 2. Intermediate (I) The “intermediate” category includes isolates with antimicrobial agent MICs that approach usually attainable blood and tissue levels and for which response rates may be lower than for susceptible isolates. The “intermediate” category implies clinical applicability in body sites where the drugs are physiologically concentrated (e.g., quinolones and ß-lactams in urine) or when a high dosage of a drug can be used (e.g., ß- lactams). The “intermediate” category also includes a “buffer zone” which should prevent small, uncontrolled technical factors from causing major discrepancies in interpretations, especially for drugs with narrow pharmacotoxicity margins. 3. Resistant (R) Resistant strains are not inhibited by the usually achievable systemic concentrations of the agent with normal dosage schedules and/or fall in the range where specific microbial resistance mechanisms are likely (e.g., ß-lactamases) and clinical efficacy has not been reliable in treatment studies. If only “S” criteria are specified: For some organism/antimicrobial combinations, the absence of resistant strains precludes defining any results categories other than “susceptible.” For strains yielding results suggestive of a “nonsusceptible” category, organism identification and antimicrobial susceptibility test results should be confirmed. Subsequently, the isolates should be saved and submitted to a reference laboratory that will confirm results using a CLSI/NCCLS reference dilution method.B. For organisms excluded from Tables 2A through 2I (e.g., Campylobacter spp., Corynebacterium spp., Bacillus spp.) studies are not yet adequate to develop reproducible, definitive standards to interpret results. These organisms may require different media, different atmospheres of incubation, or show marked strain-to-strain variation in growth rate. For these microorganisms, consultation with an infectious disease specialist is recommended for guidance in determining the need for susceptibility testing and in the interpretation of results. Published reports in the medical literature and current consensus recommendations for therapy of uncommon microorganisms may obviate the need for testing. If necessary, a dilution method usually will be the most appropriate testing method, and this may require submitting the organism to a reference laboratory. Physicians should be informed of the limitations of results and advised to interpret results with caution.Clinical and Laboratory Standards Institute. All rights reserved.© 21
  24. 24. January 2005 Vol. 25 No. 1 C. Policies regarding the generation of cumulative antibiograms should be developed in concert with the infectious disease service, infection control personnel, and the pharmacy and therapeutics committee. Under most circumstances, the percentage of susceptible and intermediate results should not be combined into the same statistics. III. Therapy-Related Comments Some of the comments in the tables relate to therapy concerns. These are denoted with an Rx symbol. It may be appropriate to include some of these comments (or modification thereof) on the patient report. An example would be inclusion of a comment on enterococcus susceptibility reports from blood cultures that “enterococcal endocarditis requires combined therapy with high- dose penicillin or high-dose ampicillin or vancomycin or teicoplanin plus gentamicin or streptomycin for bactericidal action.” Antimicrobial dosage regimens often vary widely among practitioners and institutions. In some cases, the MIC interpretive criteria rely on pharmacokinetic-pharmacodynamic data using specific human dosage regimens. In cases where specific dosage regimens are important for proper application of breakpoints, a therapy-related comment is included. IV. Verification of Patient Results Multiple test parameters are monitored by following the quality control recommendations described in this standard. However, acceptable results derived from testing quality control strains do not guarantee accurate results when testing patient isolates. It is important to review all of the results obtained from all drugs tested on a patient’s isolate prior to reporting the results. This should include but not be limited to ensuring that: 1) the antimicrobial susceptibility results are consistent with the identification of the isolate; 2) the results from individual agents within a specific drug class follow established hierarchy of activity rules (e.g., third-generation cephems are more active than first- or second-generation cephems against Enterobacteriaceae); and 3) the isolate is susceptible to those agents for which resistance has not been documented (e.g., vancomycin and Streptococcus spp.) and for which only “susceptible” interpretive criteria exist in M100. Unusual or inconsistent results should be verified by checking for the following: 1) transcription errors; 2) contamination of the test (recheck purity plates, etc.); and 3) previous results on the patient (e.g., Did the patient have the same isolate with an unusual antibiogram previously?) If a reason for the unusual or inconsistent result cannot be ascertained, a repeat of the susceptibility test or the identification or both of these is in order. Sometimes it is helpful to use an alternative test method for the repeat test. A suggested list of results that may require verification is included in Table 4. Each laboratory must develop its own policies for verification of unusual or inconsistent antimicrobial susceptibility test results. This list should emphasize those results that are highly likely to impact patient care.22 © Clinical and Laboratory Standards Institute. All rights reserved.
  25. 25. For Use With M2-A8–Disk Diffusion M100-S15V. Warning Some of the comments in the tables relate to dangerously misleading results that can occur when certain antimicrobial agents are tested and reported as susceptible against specific organisms. These are denoted with the word “Warning.” “Warning”: The following antimicrobial agent/organism combinations may appear active in vitro but are not effective clinically and should not be reported as susceptible. Location Organism Antimicrobial Agents That Must Not be Reported as Susceptible Table 2A Salmonella spp., Shigella spp. 1st- and 2nd-generation cephalosporins, and aminoglycosides Table 2C oxacillin-resistant Staphylococcus spp. all penems, cephems, and other ß- lactams such as amoxicillin-clavulanic acid, piperacillin-tazobactam, and imipenem Table 2D Enterococcus spp. aminoglycosides (except high concentrations), cephalosporins, clindamycin, and trimethoprim- sulfamethoxazoleClinical and Laboratory Standards Institute. All rights reserved.© 23
  26. 26. January 2005 Vol. 25 No. 1 Table 1. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should Be Considered for Routine Testing and Reporting on Nonfastidious Organisms by Clinical Microbiology Laboratories j Enterobacteriaceaeg Enterococcus spp.n PRIMARY TEST Pseudomonas aeruginosa Staphylococcus spp. AND REPORT g Ceftazidime l o GROUP A Ampicillin Oxacillin Penicillin or Cefazolin a Gentamicin Penicillin l ampicillin a Cephalothin Gentamicin Mezlocillin or ticarcillin Piperacillin Amikacin Amikacin Azithromycinb or s Daptomycin b clarithromycin or Linezolid erythromycinb Quinupristin- Amoxicillin-clavulanic acid Aztreonam dalfopristinr or ampicillin-sulbactam Cefoperazone Clindamycinb Vancomycinp Piperacillin-tazobactam Ticarcillin-clavulanic acid Daptomycin Cefamandole or Linezolid cefonicid or Telithromycinb cefuroxime Cefepime Cefepime Trimethoprim- REPORT SELECTIVELY sulfamethoxazole Cefmetazole Ciprofloxacin Vancomycin PRIMARY TEST g Cefoperazone Levofloxacin GROUP Be Cefotetan Cefoxitin Cefotaximeg, h, i or Imipenem g, i Meropenem ceftizoxime or ceftriaxoneg, h, i Ciprofloxacing or Tobramycin g levofloxacin Ertapenem Imipenem or meropenem Mezlocillin or piperacillin Ticarcillin Trimethoprim- sulfamethoxazoleg Aztreonam Netilmicin Chloramphenicolb Gentamicin Ceftazidime (high-level (Both are helpful resistance screen only) indicators of extended- REPORT SELECTIVELY i Ciprofloxacin or Streptomycin spectrum β-lactamases.) levofloxacin or (high-level resistanceNonfastidious Groupings SUPPLEMENTAL Chloramphenicol b, g ofloxacin screen only) M2-Disk Diffusion GROUP Cf Gatifloxacin or moxifloxacin Suggested Table 1 Kanamycin Quinupristin- dalfopristinm Gentamicin Chloramphenicolb Netilmicin Erythomycinb Tetracyclinec Rifampind Tetracyclinec Rifampind Tobramycin Tetracyclinec (These agents may be q tested for VRE) Carbenicillin Carbenicillin Lomefloxacin or Ciprofloxacin norfloxacin Levofloxacin Norfloxacin FOR URINE ONLY SUPPLEMENTAL Cinoxacin Lomefloxacin or Nitrofurantoin Nitrofurantoin Lomefloxacin or norfloxacin or GROUP U norfloxacin or ofloxacin ofloxacin Gatifloxacin Loracarbef Sulfisoxazole Tetracyclinec Nitrofurantoin Sulfisoxazole Trimethoprim Trimethoprim 24 Clinical and Laboratory Standards Institute. All rights reserved. ©
  27. 27. For Use With M2-A8–Disk Diffusion M100-S15Table 1. (Continued) j,k j,k j,kPRIMARY TEST Acinetobacter spp. Burkholderia cepacia Stenotrophomonas maltophilia AND REPORT GROUP A Ceftazidime Trimethoprim- Trimethoprim- sulfamethoxazole sulfamethoxazole Imipenem Meropenem Amikacin Ceftazidime Levofloxacin Gentamicin Tobramycin Meropenem Minocycline Minocycline Ampicillin-sulbactam Piperacillin-tazobactam Ticarcillin-clavulanate Cefepime REPORT SELECTIVELY Cefotaxime PRIMARY TEST Ceftriaxone GROUP Be Ciprofloxacin Gatifloxacin Levofloxacin Doxycycline Minocycline Tetracycline Mezlocillin Piperacillin Ticarcillin Trimethoprim- sulfamethoxazole REPORT SELECTIVELY Nonfastidious Groupings SUPPLEMENTAL M2-Disk Diffusion GROUP Cf Suggested Table 1 FOR URINE ONLY SUPPLEMENTAL GROUP U© Clinical and Laboratory Standards Institute. All rights reserved. 25
  28. 28. January 2005 Vol. 25 No. 1 Table 1. (Continued) “Warning”: The following antimicrobial agents should not be routinely reported for bacteria isolated from the CSF and which are included in this document. These antimicrobial agents are not the drugs of choice and may not be effective for treating CSF infections caused by these organisms (i.e., the bacteria included in Tables 2A to 2I): agents administered by oral route only 1st- and 2nd-generationcephalosporins (except cefuroxime sodium) clindamycin macrolides tetracyclines fluoroquinolones NOTE 1: Selection of the most appropriate antimicrobial agents to test and to report is a decision made best by each clinical laboratory in consultation with the infectious disease practitioners and the pharmacy, as well as the pharmacy and therapeutics and infection control committees of the medical staff. The lists for each organism group comprise agents of proven efficacy that show acceptable in vitro test performance. Considerations in the assignment of agents to Groups A, B, C, and U include clinical efficacy, prevalence of resistance, minimizing emergence of resistance, cost, and current consensus recommendations for first-choice and alternative drugs, in addition to the specific comments in footnotes ”e” and “f.” Tests on selected agents may be useful for infection control purposes. NOTE 2: The boxes in the table designate clusters of comparable agents that need not be duplicated in testing, because interpretive results are usually similar and clinical efficacy is comparable. In addition, an “or” designates a related group of agents that has an almost identical spectrum of activity and interpretive results, and for which cross-resistance and susceptibility are nearly complete. Therefore, usually only one of the agents within each selection box (cluster or related group) need be selected for testing. Agents that are reported must be tested, unless reporting based on testing another agent provides a more accurate result (e.g., susceptibility of staphylococci to cefazolin or cephalothin based on oxacillin testing), and they should match those included in the hospital formulary; or else the report should include footnotes indicating the agents that usually show comparable interpretive results. Unexpected results should be considered for reporting (e.g., resistance of Enterobacteriaceae to third-generation cephalosporins or imipenem). NOTE 3: Information in boldface type is considered tentative for one year.Nonfastidious Groupings Footnotes M2-Disk Diffusion General Comments Suggested Table 1 a. Cephalothin can be used to represent cephalothin, cephapirin, cephradine, cephalexin, cefaclor, and cefadroxil. Cefazolin, cefuroxime, cefpodoxime, cefprozil, and loracarbef (urinary isolates only) may be tested individually, because some isolates may be susceptible to these agents when resistant to cephalothin. b. Not routinely reported on organisms isolated from the urinary tract. c. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline and minocycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline or minocycline or both. d. Rx: Rifampin should not be used alone for chemotherapy. e. Group B represents agents that may warrant primary testing but which should be reported only selectively, such as when the organism is resistant to agents of the same class in Group A. Other indications for reporting the result might include selected specimen sources (e.g., third-generation cephalosporin for isolates of enteric bacteria from cerebrospinal fluid or trimethoprim-sulfamethoxazole for urinary tract isolates); stated allergy or intolerance, or failure to respond to an agent in Group A; polymicrobial infections; infections involving multiple sites with different microorganisms; or reports to infection control as an epidemiologic aid. 26 © Clinical and Laboratory Standards Institute. All rights reserved.
  29. 29. For Use With M2-A8–Disk Diffusion M100-S15Table 1. (Continued)f. Group C represents alternative or supplemental antimicrobial agents that may require testing in those institutions that harbor endemic or epidemic strains resistant to one or more of the primary drugs (especially in the same class, e.g., β-lactams or aminoglycosides), or for treatment of unusual organisms (e.g., chloramphenicol for some Pseudomonas spp., and chloramphenicol, erythromycin, rifampin, and tetracycline for some vancomycin-resistant enterococci), or reporting to infection control as an epidemiologic aid.Enterobacteriaceaeg. For fecal isolates of Salmonella and Shigella spp., only ampicillin, a quinolone, and trimethoprim- sulfamethoxazole should be tested and reported routinely. In addition, chloramphenicol and a third- generation cephalosporin should be tested and reported for extraintestinal isolates of Salmonella spp.h. Cefotaxime and ceftriaxone should be tested and reported on isolates from CSF in place of cephalothin and cefazolin.i. Strains of Klebsiella spp. and E. coli that produce ESBLs may be clinically resistant to therapy with penicillins, cephalosporins, or aztreonam, despite apparent in vitro susceptibility to some of these agents. Some of these strains will show zones of inhibition below the normal susceptible population but above the standard breakpoints for certain extended-spectrum cephalosporins or aztreonam; such strains may be screened for potential ESBL production by using the screening breakpoints listed in the table at the end of Table 2A, Initial Screen Test. Other strains may test intermediate or resistant by standard breakpoints to one or more of these agents. In all strains with ESBLs, the zone diameters for one or more of the extended-spectrum cephalosporins should increase in the presence of clavulanic acid as described at the end of Table 2A, Phenotypic Confirmatory Test. For all confirmed ESBL-producing strains, the test interpretation should be reported as resistant for all penicillins, cephalosporins, and aztreonam. (See Glossary I for specific agents included in the antimicrobial class, penicillins, and antimicrobial subclass, cephalosporins.)Pseudomonas aeruginosa, Acinetobacter spp., Burkholderia cepacia, and Stenotrophomonasmaltophiliaj. Non-Enterobacteriaceae except for P. aeruginosa, Acinetobacter spp., B. cepacia, and S. maltophilia should be tested by the dilution method (see M7).k. Other agents may be approved for therapy but their performance has not been sufficiently studied to establish disk diffusion breakpoints.Staphylococcus spp. Nonfastidious Groupings M2-Disk Diffusionl. Penicillin-susceptible staphylococci are also susceptible to other penicillins, cephems, and carbapenems approved for use by the FDA for staphylococcal infections. Penicillin-resistant, oxacillin-susceptible strains Suggested are resistant to penicillinase-labile penicillins but susceptible to other penicillinase-stable penicillins, β- Table 1 lactam/β-lactamase inhibitor combinations, relevant cephems, and carbapenems. (See Glossary I for specific agents included in the antimicrobial class or antimicrobial subclass indicated). Oxacillin-resistant staphylococci are resistant to all currently available β-lactam antibiotics. Thus, susceptibility or resistance to a wide array of β-lactam antibiotics may be deduced from testing only penicillin and oxacillin. Routine testing of other penicillins, β-lactamase inhibitor combinations, cephems, and carbapenems is not advised.m. For reporting against methicillin-susceptible Staphylococcus aureus.Enterococcus spp.n. Warning: For Enterococcus spp., cephalosporins, aminoglycosides (except for high-level resistance screening), clindamycin, and trimethoprim-sulfamethoxazole may appear active in vitro but are not effective clinically, and isolates should not be reported as susceptible.o. Penicillin susceptibility may be used to predict the susceptibility to ampicillin, amoxicillin, ampicillin-Clinical and Laboratory Standards Institute. All rights reserved.© 27
  30. 30. January 2005 Vol. 25 No. 1 Table 1. (Continued) sulbactam, amoxicillin-clavulanic acid, piperacillin, and piperacillin-tazobactam for non-β-lactamase- producing enterococci. For blood and cerebrospinal fluid isolates, a β-lactamase test is also recommended. Rx: Combination therapy of penicillin or ampicillin, plus an aminoglycoside, is usually indicated for serious enterococcal infections, such as endocarditis. p. Rx: If vancomycin is used for serious enterococcal infections, such as endocarditis, combined therapy with an aminoglycoside is usually indicated. q. Because of limited alternatives, chloramphenicol, erythromycin, tetracycline (or doxycycline or minocycline), and rifampin may be tested for vancomycin-resistant enterococci (VRE), and consultation with an infectious disease practitioner is recommended. r. For reporting against vancomycin-resistant Enterococcus faecium. s. For reporting against vancomycin-susceptible Enterococcus faecalis.Nonfastidious Groupings M2-Disk Diffusion Suggested Table 1 28 © Clinical and Laboratory Standards Institute. All rights reserved.
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