A History of CLSI's Work on Antimicrobial Susceptibility Testing
Through successful standards projects, CLSI (formerly NCCLS) was able to document and advance state of the art processes and procedures in the field of laboratory medicine. Through the cooperation of clinical microbiologists, laboratory industry professionals, and regulators, CLSI standards for antimicrobial susceptibility testing (AST) became a model for improving laboratory practice through voluntary consensus.
In December of 1986 NCCLS published the first edition of M100—Performance Standards for Antimicrobial Susceptibility Testing. M100 provides up-to-date AST breakpoints to laboratory professionals. This information helps health care providers treat their patients with the most effective antimicrobial drugs, as well as helping to slow antimicrobial resistance (AMR). AMR is currently one of the top global health threats. CLSI continues to publish M100 annually.
Scroll down or click the year to the left to learn more about the history of AST at CLSI.
In 1975 the first edition of Performance Standards for Antimicrobial Disc Susceptibility Tests—ASM-1, was published. This would later go on to become M100. Next near CLSI will publish the 29th edition of M100.
In 1981, the Subcommittee on Disc Diffusion Susceptibility Testing, chaired by Ronald N. Jones, MD, published the first supplement to the “Performance Standard for Antimicrobic Disc Susceptibility Testing” (M2-A2). The supplement provided new information on disc selection, interpretation, and quality control for many new drugs that had cleared the IND and NDA process at the FDA. In addition, data on interpretive disc criteria and quality control limits for older antimicrobials were included. The Subcommittee on Culture Media, co-chaired by Harry Frankel and Helen Pollock, PhD, developed an investigation protocol for the evaluation of various production lots of Mueller-Hinton agar.
The Area Committee on Microbiology, under the leadership of Arthur L. Barry, PhD, continued in 1982 to address the needs of both the manufacturer and the user. The Subcommittee on Disk Diffusion Susceptibility Testing, chaired by Ronald N. Jones, MD, issued the Second Informational Supplement to the “Performance Standard for Antimicrobial Disc Susceptibility Test” (M2-A2). The supplement contained updated interpretive criteria and quality control guidelines for several new antimicrobials and corrections of older quality control values. At that time, the supplement and the M2-A2 standard were the most widely used NCCLS standards internationally.
NCCLS also recognized the need for standardization of media, to further ensure reliable results of disk diffusion susceptibility testing. Because performance differences were observed between lots of Mueller-Hinton agar from different manufacturers, the Subcommittee on Culture Media undertook a Mueller-Hinton Agar Study project to identify a primary reference lot of standard disk diffusion susceptibility testing medium. Representative lots of Mueller-Hinton agar were solicited from seven manufacturers of dehydrated media. The testing protocol incorporated the standardized procedure in M2-A2.
Two important documents for clinical microbiology laboratories, M2-T3, the disk susceptibility standard, and M7-T, the procedure for tube (MIC) testing, were completed by the Area Committee on Microbiology, chaired by Arthur L. Barry, PhD. Both documents were substantively changed over previous editions. The Mueller Hinton project made great strides in 1983. The subcommittee identified a primary reference lot of Mueller-Hinton agar and was now in the final phase of the project.
In conjunction with the American Society for Microbiology meeting in March 1983, the committee presented a seminar on “The Current Status of Susceptibility Testing: The Role of the NCCLS Consensus Mechanism.”
The Area Committee on Microbiology, chaired by Ronald N. Jones, MD, had 16 current projects accessing antimicrobial susceptibility testing, media quality control, automation, and other areas of clinical microbiology in 1984. The committee produced the third edition of Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard (M2-A3). This document addressed the most requested test of the clinical microbiology laboratory, and the third edition contained important changes in quality control recommendations.
The committee also made significant progress to bring two other documents on susceptibility testing to the approved level: the dilution procedure for aerobic bacteria (M7) and the reference agar dilution procedure to anaerobic bacteria (M11).
In 1985, the committee produced five documents: two approved standards, a proposed standard, a proposed guideline, and a committee report.
In the area of antimicrobial susceptibility testing where the area committee’s work had been vital, the standards for a reference agar dilution procedure for testing anaerobic bacteria that grow aerobically (M7-A) were approved by NCCLS’s members and published for the first time at the approved level. These standards, along with the third approved edition of the disk diffusion standard (M2-A3) published in 1984, constituted the NCCLS authoritative “book” on antimicrobial susceptibility testing.
In antifungal susceptibility testing, the committee completed an extensive report (M20-CR) on the current state of such testing by US laboratories. This report laid the foundation for future standardization of an increasingly important area of clinical microbiology.
The first edition of M100 (M100-S) is published.
In 1987, microbiology was a busy and productive area. The area committee, chaired by Ronald N. Jones, MD, administered fourteen publications and six authorized projects in development, addressing antimicrobial, antifungal, and antimycobacterial susceptibility testing, quality assurance and performance criteria of culture media; parasitology; and other areas of clinical microbiology.
For the second straight year, a supplement to the interpretive tables in the three-document series of American National Standards on antimicrobial susceptibility testing was published under one cover. The supplement program carried out by the Subcommittee on Antimicrobial Susceptibility Testing, chaired by J. Allan Waitz, PhD, has again provided microbiology laboratories with current clinically relevant in vitro test information that has profound effects on chemotherapy.
Also published in 1987 was a guideline for manufacturers of antimicrobial agents, specifying the data needed for incorporating an agent into the interpretive tables of the NCCLS standards. This guideline, written by a subcommittee chaired by William J. Novick, PhD, greatly facilitated the evaluation of the in vitro performance of new antimicrobial agents, and contributed to the dynamic database available to the NCCLS susceptibility testing subcommittee.
The tentative edition of the standard on quality assurance for commercially prepared culture media was published in 1987. The standard, written by a subcommittee chaired by Raymond C. Bartlett, MD, has had a significant effect on the cost of quality control testing in the clinical microbiology laboratory. This success resulted from the voluntary cooperation of media manufacturers, regulatory agencies, and clinical microbiologists in addressing an important issue of laboratory practice.
At the end of the year, the area committee assumed responsibility for continued consensus review of the guideline on protection of laboratory workers from infectious disease, which would be a priority in 1988.
In 1988, the Area Committee on Microbiology, chaired by Ronald N. Jones, MD was very active in producing four new documents and having three standards accepted as American National Standards. The area committee now had 18 current publications and projects addressing antimicrobial, antifungal, and antimycobacterial susceptibility testing; quality control and performance criteria of culture media; and other areas of clinical microbiology.
For the first time in 1988, a supplement to the interpretive tables of the three-document series on antimicrobial susceptibility testing (M2-A3, M7-A, and M11-A) was published under one cover as M100-S. The supplement program was successfully used to update the information on document M2-A3, and now that all three standards were at the approved level, a combined document was prepared by a new committee, chaired by J. Allan Waitz, PhD. An important standard (M6-P) for manufacturers of Mueller-Hinton Agar, the medium recommended for use in disk susceptibility testing, was published in 1988.
Both the guideline on protection of laboratory workers and the guideline on antimicrobial susceptibility testing of anaerobic bacteria published in 1989 were in demand. The antimycobacterial susceptibility testing project, handled by a subcommittee chaired by Herbert M. Sommers, MD, offered recommendation for common culture media, standardization of drug concentrations, a method for standardizing inoculum dilutions, and clearly defined endpoints in susceptibility testing of TB-like organisms.
The ever-changing information on antimicrobial susceptibility testing was presented in its most up-to-date form in M100-S3, which was published in 1991. The Subcommittee on Antimicrobial Susceptibility Testing, chaired by James H. Jorgensen, PhD, revised the tables for M2, M7, and M11 for inclusion in this information supplement.
In response to the concern about risk of exposure to infectious disease, the Subcommittee on Protection of Laboratory Workers, chaired by Stanley Bauer, MD, updated M29 to the second edition tentative level. The new document incorporated information about chemoprophylaxis and also included new recommendations from CDC about protection of patients during invasive procedures.
The authorized project on antifungal reference methodology was being developed by the Subcommittee on Antifungal Susceptibility Testing chaired by John N. Galgiani, MD. The Subcommittee on Microbiological Tests and Reagent, chaired by Patricia Charache, MD, was working on development of a project which was to provide performance and quality control standards for working reagents and test systems used in microbiology laboratory procedures.