ABSTRACT
Introduction. The therapeutic options to treat Acinetobacter baumannii infections are very limited.Aim. Our aim was to evaluate the activity of sulbactam combined directly with avibactam or the ampicillin-sulbactam/ceftazidime-avibactam combination against extensively drug-resistant A. baumannii isolates.Methodology. Extensively drug-resistant A. baumannii isolates (n=127) collected at several South American hospitals were studied. Synergy with the sulbactam/avibactam combination was assessed in all isolates using the agar dilution method. Avibactam was used at a fixed concentration of 4 mg l-1. A disc diffusion synergy test was also performed. Synergy by a time-kill experiment was performed in a selected isolate.Results. Synergy with sulbactam/avibactam was demonstrated in 124 isolates and it showed MIC values ≤4 mg l-1. This synergy was not detected in the three New Delhi metallo-ß-lactamase-harbouring isolates. Similar results were observed with the disc diffusion synergy test of ampicillin-sulbactam/ceftazidime-avibactam. In the time-kill experiments, sulbactam/avibactam showed a rapid synergistic and bactericidal activity in ampicillin-sulbactam-resistant isolates.Conclusions. This study demonstrated that the sulbactam/avibactam combination displayed synergistic activity against A. baumannii isolates. This synergy was observed when both inhibitors were also used as part of the commercially available combinations: ampicillin-sulbactam and ceftazidime-avibactam.
Subject(s)
Acinetobacter Infections/therapy , Azabicyclo Compounds/metabolism , Sulbactam/pharmacology , Acinetobacter Infections/metabolism , Acinetobacter baumannii/metabolism , Ampicillin/pharmacology , Anti-Bacterial Agents/pharmacology , Azabicyclo Compounds/pharmacology , Ceftazidime/pharmacology , Drug Combinations , Drug Resistance, Bacterial/drug effects , Drug Resistance, Multiple, Bacterial/drug effects , Drug Therapy, Combination/methods , Humans , Microbial Sensitivity Tests , Thienamycins/pharmacologyABSTRACT
The objective of this study was to compare the performance of disk diffusion and agar dilution for the determination of susceptibility to ampicillin/sulbactam (SAM), ceftazidime, cefepime, imipenem, meropenem, polymyxin B and tigecycline of 121 Acinetobacter baumannii clinical isolates. The antimicrobial susceptibility testing methods were performed as recommended by the Clinical and Laboratory Standards Institute (CLSI). For SAM, in addition the Etest method was performed according to the manufacturer's instructions. The error rates for the antimicrobial agents for 121 isolates tested were within the acceptable ranges established by the CLSI, with the exception of SAM and polymyxin B. For polymyxin B, there were 1.7% very major errors and for SAM there were 15% comparing disk diffusion with agar dilution. The very major error rate of SAM comparing the Etest with agar dilution was 10%. These high observed rates of very major error cast doubt on the disk diffusion and Etest techniques as appropriate methods for detecting resistance to SAM.