The impact of inoculum size on the activity of cefoperazone-sulbactam against multidrug resistant organisms

Objectives: This study aims to assess the in vitro activity of cefoperazone alone and different cefoperazone-sulbactam ratios against different inoculum sizes of multidrug resistant organisms. Methods: Minimum inhibitory concentrations (MICs) of cefoperazone, cefoperazone-sulbactam at fixed ratio of 1: 1 and 2: 1 against a normal inoculum size of 5 x 10(5) CFU/ml and a high inoculum size of 5 x 10(7) CFU/ml were measured. Results: Each 33 isolates of extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli, ESBL-producing Klebsiella pneumoniae, carbapenem-resistant E. coli, and carbapenem-resistant Pseudomonas aeruginosa and a total of 122 isolates of carbapenem-resistant Acinetobacter baumannii were collected. After the addition of sulbactam at a 1: 1 ratio, most MIC50 and MIC90 values decreased. Cefoperazone-sulbactam at a 1: 1 ratio had a higher susceptibility rate against ESBL-producing E. coli, carbapenem-resistant E. coli, and carbapenem-resistant A. baumannii than cefoperazone-sulbactam at a 2: 1 ratio (all P < 0.05). For ESBL-producing E. coli, the susceptibility rate of cefoperazone-sulbactam at ratios of (1: 1) and (2: 1) decreased from 97.0 to 87.9% and 90.9 to 60.6%, for normal to high inoculum, respectively. For ESBL-producing K. pneumoniae, both susceptibility rate of cefoperazone-sulbactam at ratios of (1: 1) and (2: 1) decreased from 75.8%, and 63.6% at normal inoculum to 51.5% and 42.4% at high inoculum. Conclusions: Cefoperazone-sulbactam at a 1: 1 ratio has greater in vitro activity against most multidrug resistant organisms than cefoperazone-sulbactam at a 2: 1 ratio. Such combinations were not influenced by the inoculum size of ESBL-producing E. coli and K. pneumoniae and could be a therapeutic option for treating severe infections. Copyright (C) 2017, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC.