An increasing number of untreatable infections are recorded every year. Many studies have focused their efforts on developing new β-lactamase inhibitors to treat multi-drug resistant (MDR) isolates. In the present study, sulbactam/avibactam and sulbactam/relebactam combination were tested against 187 multi-drug resistant (MDR) Acinetobacter clinical isolates; both sulbactam/avibactam and sulbactam/relebactam restored sulbactam activity. A decrease ≥2 dilutions in sulbactam MICs was observed in 89% of the isolates when tested in combination with avibactam. Sulbactam/relebactam was able to restore sulbactam susceptibility in 40% of the isolates. In addition, the susceptibility testing using twenty-three A. baumannii AB5075 knockout strains revealed potential sulbactam and/or sulbactam/avibactam target genes. We observed that diazabicyclooctanes (DBOs) β-lactamase inhibitors combined with sulbactam restore sulbactam susceptibility against carbapenem-resistant Acinetobacter clinical isolates. However, relebactam was not as effective as avibactam when combined with sulbactam. Exploring novel combinations may offer new options to treat Acinetobacter spp. infections, especially for widespread oxacillinases and metallo-β-lactamases (MBLs) producers.
Carbapenems are commonly used to treat infections caused by multidrug-resistant (MDR) bacteria. Unfortunately, carbapenem resistance is increasingly reported in many gram-negative bacteria, especially Acinetobacter baumannii. Diazabicyclooctane (DBO) β-lactamase inhibitors, such as avibactam (AVI), when combined with sulbactam successfully restore sulbactam susceptibility against certain carbapenem-resistant A. baumannii (CRAB) isolates. In the present study, we tested zidebactam, a novel DBO with an additional mechanism of action, in combination with sulbactam against CRAB isolates, including strains that exhibited resistance against sulbactam/avibactam combination. A panel of 43 geographically and genetically distinct CRAB isolates recovered from different hospitals and containing different mechanisms of resistance were included in the present study. We also tested three reference strains (AB0057, AB5075, and AYE). Minimum inhibitory concentrations (MICs) for sulbactam (range 0.12–512 mg/l) and sulbactam plus 4 mg/l zidebactam were performed using microdilution according to CLSI Standards. A decrease ≥2 dilutions in sulbactam MICs was observed in 84% of the isolates when tested in combination with zidebactam. The sulbactam/zidebactam combination was able to restore sulbactam susceptibility in 91% of the isolates, including isolates that were resistant to sulbactam/avibactam combination. These data encouraged us to further explore sulbactam/zidebactam in other experimental models especially against CRAB isolates resistant to other DBOs.
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