Sulbactam-durlobactam susceptibility test method development and quality control ranges for MIC and disk diffusion...

Area of Science:

• Microbiology
• Clinical Laboratory Science

Background:

• Sulbactam-durlobactam is a novel combination therapy targeting hospital-acquired and ventilator-associated bacterial pneumonia caused by Acinetobacter baumannii-calcoaceticus complex (ABC).
• Durlobactam, a potent β-lactamase inhibitor, restores sulbactam's activity against multidrug-resistant ABC by inhibiting Ambler classes A, C, and D serine β-lactamases.

Purpose of the Study:

• To establish validated antimicrobial susceptibility testing (AST) methods for sulbactam-durlobactam.
• To define quality control (QC) ranges for broth microdilution (MIC) and disk diffusion tests.

Main Methods:

• Evaluated sulbactam-durlobactam combinations using genetically characterized A. baumannii isolates.
• Determined optimal MIC testing concentrations and disk diffusion criteria for discriminating susceptible and resistant strains.
• Conducted multi-laboratory QC studies using A. baumannii NCTC 13304 according to CLSI M23 Tier 2 criteria.

Main Results:

• MIC testing with doubling dilutions of sulbactam and a fixed 4 µg/mL durlobactam concentration showed optimal discrimination.
• A 10/10 µg sulbactam/durlobactam disk concentration demonstrated the best discrimination and MIC correlation.
• CLSI-approved QC ranges were established: 0.5/4-2/4 µg/mL for MIC and 24-30 mm for disk diffusion.

Conclusions:

• Established accurate and reproducible AST methods for sulbactam-durlobactam.
• These validated methods will support clinical laboratories in identifying patients who may benefit from sulbactam-durlobactam treatment.
• The defined QC ranges ensure reliable susceptibility testing for Acinetobacter baumannii infections.