Proposed Meropenem Breakpoints for Interpretation of Antimicrobial Susceptibility Testing of Bacteria Isolated From...

Area of Science:

• Veterinary Pharmacology
• Antimicrobial Resistance
• Clinical Microbiology

Background:

• Meropenem, a carbapenem antibiotic, is rarely used in veterinary medicine.
• Lack of veterinary-specific carbapenem breakpoints hinders monitoring of carbapenem-resistant Enterobacterales (CRE) in animals.
• The Clinical and Laboratory Standards Institute (CLSI) lacks established breakpoints for veterinary use.

Purpose of the Study:

• To address the deficiency in veterinary antimicrobial susceptibility testing (AST) standards for meropenem.
• To propose clinical MIC breakpoints for meropenem for bacteria isolated from dogs.
• To support clinical laboratories, standard-setting organizations, and surveillance programs for antimicrobial resistance.

Main Methods:

• Collected pharmacokinetic data from published studies on meropenem in dogs.
• Utilized a forecasting program to conduct 10,000 Monte Carlo Simulations.
• Simulated various dosages to achieve a 90% Probability of Target Attainment (PTA) for unbound drug concentration above the Minimum Inhibitory Concentration (MIC).

Main Results:

• A meropenem MIC of ≤1 μg/mL for Enterobacterales can be achieved with 20-30 mg/kg IV every 8h or 10 mg/kg every 6h.
• For Pseudomonas aeruginosa with an MIC of ≤2 μg/mL, a dose of 20-30 mg/kg every 6h is required.
• Proposed breakpoints: Enterobacterales ≤1 μg/mL (Susceptible), 2 μg/mL (Intermediate), ≥4 μg/mL (Resistant); P. aeruginosa ≤2 μg/mL (S), 4 μg/mL (I), ≥8 μg/mL (R).

Conclusions:

• Established proposed meropenem MIC breakpoints for AST in dogs.
• These breakpoints are crucial for monitoring and surveillance of CRE and P. aeruginosa.
• The proposed breakpoints will aid veterinary clinical laboratories in accurate susceptibility testing.