Comparative in vitro activity of sulbactam with avibactam or durlobactam against carbapenem-resistant Acinetobacter baumannii

Objective To determine the in vitro activity of sulbactam in combination with avibactam or durlobactam with and without meropenem or imipenem against carbapenem-resistant Acinetobacter baumannii clinical isolates. Methods Standardized susceptibility testing by broth microdilution was performed to determine MICs for imipenem, meropenem and sulbactam alone, and for combinations including sulbactam/avibactam, sulbactam/durlobactam, sulbactam/avibactam/meropenem, sulbactam/avibactam/imipenem, sulbactam/durlobactacm/meropenem and sulbactam/durlobactam/imipenem. Whole-genome sequencing was also performed to compare MICs to key resistance determinants, including mutations in penicillin-binding proteins (PBPs). Results Median sulbactam/durlobactam and sulbactam/avibactam MICs were 2 and 16 mg/L, respectively. Imipenem potentiated the in vitro activity of both combinations to a greater extent than meropenem corresponding to median sulbactam/durlobactam/imipenem and sulbactam/avibactam/imipenem MICs of 1 and 8 mg/L, respectively. Carbapenem combinations were more active than combinations without a carbapenem against isolates with PBP3 mutations. Conclusions These data show that imipenem potentiates sulbactam-based combinations to a greater extent than meropenem; however, future studies are needed to define how these data should be applied in clinical practice.