In vitro activity of ceftolozane/tazobactam against clinical isolates of Pseudomonas aeruginosa in the planktonic and biofilm states

Diagn Microbiol Infect Dis. 2016 Jul;85(3):356-359. doi: 10.1016/j.diagmicrobio.2016.02.014. Epub 2016 Feb 18.

Abstract

Pseudomonas aeruginosa causes a variety of life-threatening infections, some of which are associated with planktonic and others with biofilm states. Herein, we tested the combination of the novel cephalosporin, ceftolozane, with the β-lactamase inhibitor, tazobactam, against planktonic and biofilm forms of 54 clinical isolates of P. aeruginosa, using cefepime as a comparator. MIC values were determined following Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum biofilm inhibitory concentration (MBIC) values were determined using biofilm-laden pegged lids incubated in antimicrobial challenge plates containing varying concentrations of ceftolozane/tazobactam. Pegged lids were then incubated in growth recovery plates containing cation-adjusted Mueller-Hinton broth to determine the minimum biofilm bactericidal concentration (MBBC). Ceftolozane/tazobactam was highly active against planktonic P. aeruginosa, with all 54 isolates studied testing susceptible (MIC ≤4/4μg/mL). On the other hand, 51/54 biofilm P. aeruginosa had MBICs ≥16/4μg/mL, and all 54 isolates had MBBCs >32μg/mL. Of the 54 isolates, 45 (83.3%) tested susceptible to cefepime, with the MIC50/MIC90 being 4/16μg/mL, respectively, and the MBIC90 and MBBC90 both being >256μg/mL. Although ceftolozane/tazobactam is a promising antimicrobial agent for the treatment of P. aeruginosa infections, it is not highly active against P. aeruginosa biofilms.

Keywords: Biofilm; Ceftolozane; Pseudomonas aeruginosa; Tazobactam.

MeSH terms

  • Anti-Infective Agents, Urinary / pharmacology*
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Cephalosporins / pharmacology*
  • Humans
  • Microbial Sensitivity Tests
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / pharmacology
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / isolation & purification
  • Pseudomonas aeruginosa / physiology*
  • Tazobactam
  • beta-Lactamase Inhibitors / pharmacology*

Substances

  • Anti-Infective Agents, Urinary
  • Cephalosporins
  • beta-Lactamase Inhibitors
  • ceftolozane, tazobactam drug combination
  • Penicillanic Acid
  • Tazobactam