In vitro activity of cefoperazone and cefoperazone-sulbactam against carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa

Background: This study aimed to investigate the in vitro activity of cefoperazone–sulbactam against carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa , and to evaluate the antibiotic resistance mechanisms of these bacteria. Materials and methods: In total, 21 isolates of carbapenem-resistant P. aeruginosa and 15 isolates of carbapenem-resistant A. baumannii with different pulsed-field gel electrophoresis types were collected for assessment of the in vitro antibacterial activities of cefoperazone and cefoperazone–sulbactam and the associated resistance mechanisms of the bacteria. Results: For carbapenem-resistant P. aeruginosa , the minimum inhibitory concentration (MIC) value and antibiotic susceptibility rate were similar for cefoperazone and cefoperazone–sulbactam (at 1:1 and 2:1 ratios). In contrast, for carbapenem-resistant A. baumannii , the MIC values, including the MIC range, MIC that inhibited 50% of isolates (MIC 50 ) and MIC that inhibited 90% of isolates (MIC 90 ), were reduced after treatment with sulbactam and cefoperazone. We screened resistance genes, including VIM-2, OXA-2 and OXA-10, in 21 carbapenem-resistant P. aeruginosa isolates. Only one (4.8%) of the isolates showed expression of VIM-2, and neither the OXA-2 nor the OXA-10 gene was detected. However, 20 (95.2%) isolates among the carbapenem-resistant P. aeruginosa isolates selected for oprD sequencing showed the phenomenon of nucleotide substitution or deletion. Among 15 carbapenem-resistant A. baumannii isolates, we found that ten (66.7%) isolates had concomitant expression of the OXA-23 and ISAba1-OXA-23 genes, and six (40.0%) isolates had expression of the OXA-24-like gene. All 15 isolates had OXA-51-like gene expression, and only 1 (6.7%) isolate had ISAba1-OXA-51-like gene expression. None of the isolates contained the IMP-1, IMP-8, KPC, NDM, VIM-1 or OXA-48 genes. Conclusion: The in vitro antibacterial activity of cefoperazone against carbapenem-resistant A. baumannii can be enhanced by adding sulbactam to cefoperazone, but the addition does not affect carbapenem-resistant P. aeruginosa . This significant difference can be explained by the different resistance mechanisms of carbapenem-resistant A. baumannii and P. aeruginosa . Keywords: cefoperazone–sulbactam, Acinetobacter baumannii , Pseudomonas aeruginosa