Objectives: To evaluate sulbactam/avibactam and sulbactam/relebactam combination to restore sulbactam activity against carbapenem-resistant Acinetobacter spp. clinical isolates.
Methods: 187 multi-drug resistant (MDR) Acinetobacter clinical isolates, including 175 carbapenem-resistant Acinetobacter clinical isolates, were used to determine the effect of sulbactam combinations. In vitro activities of sulbactam/avibactam and sulbactam/relebactam were determined by three different susceptibility assays.
Results: A decrease >= 2 dilutions in sulbactam MICs was observed in 89 % of the isolates when was tested in combination with avibactam. Against this collection of isolates, sulbactam/avibactam had a MIC50/MIC90 of 2/32 μg/ml compared to a MIC50/MIC90 of 16/>64 μg/ml for sulbactam alone. About 90% of oxacillinase producing carbapenem-resistant isolates were inhibited by 4 mg/L of sulbactam/avibactam, compared to only 9% with sulbactam alone. Sulbactam combined with relebactam was able to restore sulbactam susceptibility only in 40% of the isolates. In addition, Acinetobacter ATCC 17978 cells expressing blaNDM-1 and/or blaOXA-23 did not show significant changes in sulbactam MIC when either NDM-1, OXA-23 or both of them together were being expressed, suggesting another target for sulbactam/avibactam synergism.
Conclusions: In the present study, we show that avibactam combine with sulbactam successfully restores sulbactam susceptibility in ESBL producer and carbapenem-
resistant Acinetobacter clinical isolates. Relebactam was not as effective as avibactam when combined with sulbactam. We observed that “switching” avibactam’s β-lactam partner from ceftazidime to sulbactam, a new option could be explored to treat Acinetobacter spp. infections with limited therapeutic options, especially for pandemic oxacillinases and MBLs producers.