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

Abstract 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 × 10 5  CFU/ml and a high inoculum size of 5 × 10 7  CFU/ml were measured. Results Each 33 isolates of extended-spectrum β-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 MIC 50 and MIC 90 values decreased. Cefoperazone-sulbactam at a 1:1 ratio had a higher susceptibility rate against ESBL-producing E. coli , carbapenem-resistant E. c oli, and carbapenem-resistant A. baumannii than cefoperazone-sulbactam at a 2:1 ratio (all P  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.