Abstract Our objective was to compare the in vitro activity of sulbactam and sulbactam/durlobactam against carbapenem-resistant A. baumannii isolates carrying bla OXA−23 or both bla OXA−23 and bla PER-1 genes. We also aimed to investigate the possible mechanisms of resistance in sulbactam/durlobactam resistant isolates. Twenty-four carbapenem-resistant A. baumannii isolates (12 carrying bla OXA−23 , 12 carrying bla OXA−23 and bla PER-1 ) were included in the study. Genetic relations among isolates were determined by Pulsed-Field Gel Electrophoresis (PFGE). MICs of sulbactam and sulbactam/durlobactam were determined by gradient diffusion method. Whole-genome sequencing was performed on sulbactam/durlobactam resistant isolates. Among 24 isolates, PFGE revealed 5 distinct major clusters. One (4.2%) and 22 (91.7%) of isolates were susceptible to sulbactam and sulbactam/durlobactam, respectively. Sulbactam MIC 50 value for isolates carrying bla OXA−23 plus bla PER-1 (32 mg/L) were 2.7 fold higher than that for isolates carrying bla OXA−23 (12 mg/L). However, similar sulbactam/durlobactam MIC 50 values were observed for isolates carrying bla OXA−23 plus bla PER-1 (1 mg/L) or bla OXA−23 (1.5 mg/L). Both the two sulbactam/durlobactam resistant isolates had mutations in PBP3 gene. The isolate with sulbactam/durlobactam MIC of 12 mg/L had A515V and C1546T mutations in PBP3 gene. Also, the AdeN (repressor of AdeIJK efflux system) was absent in this isolate. The isolate with sulbactam/durlobactam MIC of >64 mg/L had one amino acid insertion at position 374 (-374D) in PBP3. Sulbactam/durlobactam demonstrated high activity against carbapenem-resistant A. baumannii isolates. Sulbactam/durlobactam resistance was likely due to mutations in PBP3 gene. Overexpression of AdeIJK efflux system may also have contributed to resistance in one isolate.
Mirza et al. (Fri,) studied this question.
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