Strategies for Updating Piperacillin-Tazobactam Breakpoints

Area of Science:

• Clinical Microbiology
• Antimicrobial Resistance
• Infectious Diseases

Background:

• Accurate antimicrobial susceptibility testing (AST) is vital for guiding effective antibiotic therapy.
• Piperacillin-tazobactam (TZP) is a critical antibiotic for treating infections caused by Enterobacterales.
• Evolving resistance patterns necessitate regular updates to clinical breakpoints for AST interpretation.

Purpose of the Study:

• To evaluate the performance of three U.S. Food and Drug Administration (FDA)-cleared AST devices for piperacillin-tazobactam (TZP) MIC testing.
• To compare device performance against the reference broth microdilution method for Enterobacterales.
• To assess the impact of updated Clinical and Laboratory Standards Institute (CLSI) breakpoints on TZP susceptibility categorization.

Main Methods:

• A multisite study was conducted to evaluate three FDA-cleared AST devices.
• Piperacillin-tazobactam (TZP) MICs were determined for Enterobacterales isolates.
• Results were compared to the reference broth microdilution method using both FDA and CLSI breakpoints.

Main Results:

• Overall performance of the three AST devices was comparable when using either FDA or CLSI TZP breakpoints.
• Failure to implement current CLSI breakpoints led to the misclassification of up to 20% of TZP-resistant isolates as susceptible.
• The study highlights discrepancies in susceptibility reporting based on breakpoint versions.

Conclusions:

• Timely adoption of updated CLSI breakpoints for piperacillin-tazobactam (TZP) is essential for accurate AST.
• Outdated breakpoints can lead to significant underestimation of resistance in Enterobacterales.
• Strategies for implementing updated breakpoints are necessary to ensure appropriate patient management and antimicrobial stewardship.