Comparative activity of sulbactam and sulbactam/durlobactam against carbapenem-resistant A. baumannii isolates producing OXA-23 or OXA-23 plus PER-1 enzymes

OpenAlex İngilizce

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.