Appropriate composites of cefoperazone–sulbactam against multidrug-resistant organisms

Objectives: This study aims to assess the in vitro activity of different cefoperazone–sulbactam ratios against different multidrug-resistant organisms (MDROs). Materials and methods: Minimum inhibitory concentrations (MICs) and susceptibility rates of cefoperazone, sulbactam and cefoperazone–sulbactam at fixed ratios of 2:1, 1:1 and 1:2 against 344 MDRO clinical isolates, including extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (n=58), ESBL-producing Klebsiella pneumoniae (n=58), carbapenem-resistant Enterobacteriaceae (n=57), carbapenem-resistant Pseudomonas aeruginosa (n=49) and carbapenem-resistant Acinetobacter baumannii (n=122), were measured. Results: Combined treatment with sulbactam and cefoperazone resulted in decreased MIC 50 values across all MDROs, as well as decreases in most MIC 90 values, except for carbapenem-resistant Enterobacteriaceae and carbapenem-resistant P. aeruginosa (MIC 90 values remained >64 mg/L). Susceptibility rates of treatment with cefoperazone alone against all MDROs were much lower than that of cefoperazone–sulbactam combination (all P <0.05), except in carbapenem-resistant P. aeruginosa . Additionally, the susceptibility rate gradually increased as the ratio of cefoperazone–sulbactam was adjusted from 2:1 to 1:1 and to 1:2 for carbapenem-resistant Enterobacteriaceae, ESBL-producing K. pneumoniae and carbapenem-resistant A. baumannii . There were no significant ratio-dependent changes in susceptibility rates with cefoperazone–sulbactam in carbapenem-resistant P. aeruginosa . Conclusion: Adding sulbactam enhances cefoperazone activity against most MDROs excluding carbapenem-resistant P. aeruginosa , and the activity of cefoperazone–sulbactam against these MDROs is greatest at a ratio of 1:2, followed by ratios of 1:1 and 2:1. Keywords: cefoperazone–sulbactam, extended-spectrum β-lactamases, Escherichia coli , Klebsiella pneumoniae , multidrug-resistant organisms