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

J Microbiol Immunol Infect. 2018 Apr;51(2):207-213. doi: 10.1016/j.jmii.2017.08.026. Epub 2017 Oct 6.

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 × 105 CFU/ml and a high inoculum size of 5 × 107 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 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.

Keywords: Cefoperazone-sulbactam; Escherichia coli; Extended-spectrum β-lactamases; Inoculum size; Klebsiella pneumoniae.

MeSH terms

  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Carbapenems / pharmacology
  • Cefoperazone / pharmacology*
  • Drug Resistance, Multiple, Bacterial / physiology
  • Escherichia coli / drug effects*
  • Escherichia coli / isolation & purification
  • Humans
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / isolation & purification
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / isolation & purification
  • Sulbactam / pharmacology*
  • beta-Lactam Resistance / physiology
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Cefoperazone
  • beta-Lactamases
  • Sulbactam