Evaluation of Ceftolozane-Tazobactam in Combination with Meropenem against Pseudomonas aeruginosa Sequence Type 175 in a Hollow-Fiber Infection Model

Antimicrob Agents Chemother. 2018 Apr 26;62(5):e00026-18. doi: 10.1128/AAC.00026-18. Print 2018 May.

Abstract

The aim of this study was to investigate the efficacy of ceftolozane-tazobactam in combination with meropenem against an extensively drug-resistant (XDR) Pseudomonas aeruginosa high-risk clone, sequence type 175, isolated in a Spanish university hospital. A 14-day hollow-fiber infection model was used to simulate clinical exposure of the two drug regimens alone and in combination, and serial samples were collected to determine drug concentrations and CFU counts. The untreated control failed, as did each study regimen when administered alone. However, when ceftolozane-tazobactam was administered in combination with meropenem, there was a >4-log10 CFU/ml bacterial density reduction and suppression of resistance for the duration of the study. These data suggest that ceftolozane-tazobactam plus meropenem may be a useful combination for treating XDR P. aeruginosa.

Keywords: Pseudomonas aeruginosa; multidrug resistance; pharmacokinetics/pharmacodynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cephalosporins / pharmacology*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Meropenem / pharmacology*
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects*
  • Tazobactam / pharmacology*

Substances

  • Cephalosporins
  • ceftolozane, tazobactam drug combination
  • ceftolozane
  • Meropenem
  • Tazobactam