Amoxicillin-Clavulanate Breakpoints Against Enterobacterales: Rationale for Revision by the Clinical and Laboratory Standards Institute.

Amoxicillin-clavulanate (AMC) is among the most frequently prescribed antibiotics globally. It has broad antibacterial activity against gram-positive, gram-negative, and anaerobic bacteria and has been used to treat infections caused by a broad range of pathogens. AMC breakpoints against Enterobacterales were initially set in the 1980s. However, since that time, increases in antibiotic resistance, advances in pharmacokinetic/pharmacodynamic analyses, and publication of additional clinical data prompted a reassessment by the Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing. Based on this contemporary reappraisal, the CLSI retained the Enterobacterales breakpoints but revised comments regarding dosing associated with use of the AMC breakpoints in the 2022 supplement of M100. This viewpoint provides insight into the CLSI breakpoint reevaluation process and summarizes the data and rationale used to support these revisions to the AMC Enterobacterales breakpoint.
Competing Interests: Potential conflicts of interest. N. N. reports support from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (under award K23AI159396); honoraria from Astellas Pharma and Beckman Coulter; and research contracts with Merck and Shionogi Inc. E. W. reports honoraria from AbbVie Inc, Astellas Pharma, Ferring Pharmaceuticals, Melinta Therapeutics, Shionogi Inc, and Venatorx Pharmaceuticals. C. G. G. is immediate past-chair of the European Committee on Antimicrobial Susceptibility Testing. A. J. M. serves as a scientific advisor for Cepheid, DayZero Diagnostics and OpGen; and previously served as a scientific advisor for Merck, Qpex Biopharma, Venatorx Pharmaceuticals, and Melinta Therapeutics. N. M. M. reports research contracts from Cepheid, Inc and Abbott Molecular paid to his institution outside the submitted work; honoraria from the American Society for Clinical Laboratory Science; and serving as a member of the American Society for Clinical Laboratory Science Board of Directors and as a member of the Microbiology Resource Committee for the College of American Pathologists. All authors serve as unpaid volunteers for the Clinical and Laboratory Standards Institute. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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