In Vitro Susceptibility of Multidrug-Resistant Pseudomonas aeruginosa following Treatment-Emergent Resistance to Ceftolozane-Tazobactam

Antimicrob Agents Chemother. 2021 May 18;65(6):e00084-21. doi: 10.1128/AAC.00084-21. Print 2021 May 18.

Abstract

We compared the in vitro susceptibility of multidrug-resistant Pseudomonas aeruginosa isolates collected before and after treatment-emergent resistance to ceftolozane-tazobactam. Median baseline and postexposure ceftolozane-tazobactam MICs were 2 and 64 μg/ml, respectively. Whole-genome sequencing identified treatment-emergent mutations in ampC among 79% (11/14) of paired isolates. AmpC mutations were associated with cross-resistance to ceftazidime-avibactam but increased susceptibility to piperacillin-tazobactam and imipenem. A total of 81% (12/16) of ceftolozane-tazobactam-resistant isolates with ampC mutations were susceptible to imipenem-relebactam.

Keywords: Pseudomonas aeruginosa; antibiotic resistance; ceftolozane-tazobactam; imipenem-relebactam.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Cephalosporins / pharmacology
  • Drug Resistance, Multiple, Bacterial / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Pseudomonas Infections* / drug therapy
  • Pseudomonas aeruginosa* / genetics
  • Tazobactam / pharmacology

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • ceftolozane
  • Tazobactam