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.
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 email@example.com or +610.688.0100 for standard or guideline. additional information on committee participation.
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
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.
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
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
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: firstname.lastname@example.org; Website:www.clsi.org.10
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
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
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
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
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
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