Appropriate composites of cefoperazone–sulbactam against multidrug-resistant organisms

Chih-Cheng Lai,1 Chi-Chung Chen,2,3 Ying-Chen Lu,3 Tsuey-Pin Lin,4 Yin-Ching Chuang,2,5 Hung-Jen Tang4,6 1Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, 2Department of Medical Research, Chi Mei Medical Center, Tainan, 3Department of Food Science, National Chiayi University, Chiayi, 4Department of Health and Nutrition, Chia-Nan University of Pharmacy and Science, 5Department of Internal Medicine, Chi Mei Medical Center, Liouying, 6Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan 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 MIC50 values across all MDROs, as well as decreases in most MIC90 values, except for carbapenem-resistant Enterobacteriaceae and carbapenem-resistant P. aeruginosa (MIC90 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