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

Area of Science:

• Microbiology
• Infectious Diseases
• Clinical Pharmacology

Background:

• Amoxicillin-clavulanate (AMC) is a widely used antibiotic with broad-spectrum activity.
• Established breakpoints for Enterobacterales were set in the 1980s.
• Increased antibiotic resistance and new data necessitated a review.

Purpose of the Study:

• To reevaluate the Clinical and Laboratory Standards Institute (CLSI) breakpoints for amoxicillin-clavulanate against Enterobacterales.
• To provide insight into the CLSI breakpoint reassessment process.
• To summarize the rationale behind revised dosing comments.

Main Methods:

• Review of contemporary pharmacokinetic/pharmacodynamic data.
• Analysis of updated clinical data.
• Expert subcommittee reappraisal of existing breakpoints.

Main Results:

• CLSI retained the existing Enterobacterales breakpoints for amoxicillin-clavulanate.
• Revised comments regarding dosing associated with AMC breakpoints were published in the 2022 M100 supplement.
• The reevaluation process considered current antibiotic resistance trends.

Conclusions:

• The established breakpoints for amoxicillin-clavulanate against Enterobacterales are still considered valid.
• Updated dosing recommendations aim to optimize AMC therapy in light of current evidence.
• This reassessment highlights the dynamic nature of antimicrobial susceptibility testing guidelines.