Ceftolozane-tazobactam and ceftazidime-avibactam activity against β-lactam-resistant Pseudomonas aeruginosa and extended-spectrum β-lactamase-producing Enterobacterales clinical isolates from U.S. medical centres

Elizabeth B. Hirsch, Hunter V. Brigman, Paola C. Zucchi, Alice Chen, Jadyn C. Anderson, George M. Eliopoulos, Nicole Cheung, Adam Gilbertsen, Ryan C. Hunter, Christopher L. Emery, Tiffany E. Bias

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Despite availability of ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) for several years, the individual spectrum of activity of each agent may not be widely known. We compared the activity of C/T and CZA against convenience samples of 119 extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and 60 β-lactam-resistant Pseudomonas aeruginosa clinical isolates collected from three U.S. institutions. Methods: Minimal inhibitory concentrations (MICs) for C/T and CZA were determined by broth microdilution. Molecular identification of nine β-lactamase gene targets was conducted for Enterobacterales and P. aeruginosa isolates with increased MICs to C/T or CZA. Results: More than 90% of Enterobacterales isolates demonstrated susceptibility to both C/T and CZA, in contrast to the other traditional β-lactam agents tested, which were much less active. The MIC50/90 values were nearly equivalent between agents. The most common β-lactamase genes identified in Enterobacterales isolates with MIC values ≥2 mg/L were the CTX-M-1 group (85%) and CMY-2-like (23%) β-lactamases. Both agents were active against >80% of β-lactam-resistant P. aeruginosa isolates tested, most of which had oprD mutations identified. One P. aeruginosa isolate was positive for a Klebsiella pneumoniae carbapenemase-type gene but remained meropenem-susceptible. The MIC50 values were four-fold lower in favour of C/T (1 mg/L vs. 4 mg/L) against P. aeruginosa. Conclusions: Our data suggest that either agent may be a reasonable choice for centres with a high proportion of ESBL producers; however, C/T may have improved activity against P. aeruginosa and may be preferred in institutions with a higher frequency of resistant pseudomonal isolates.

Original languageEnglish (US)
Pages (from-to)689-694
Number of pages6
JournalJournal of Global Antimicrobial Resistance
Volume22
DOIs
StatePublished - Sep 2020

Bibliographical note

Funding Information:
This study was funded through the Merck Investigator Studies Program (to EBH) and the University of Minnesota Undergraduate Research Opportunities Program (to JCA).

Funding Information:
TEB is currently an employee of Nabriva Therapeutics and has received research funding from Merck . GME has received consulting honoraria from Melinta Therapeutics and Nabriva Therapeutics . EBH has received research funding from Merck, and advisory board honoraria from Paratek Pharmaceuticals and Nabriva Therapeutics. All other authors: none to declare.

Keywords

  • ESBL
  • MDR
  • Multidrug-resistant
  • beta-lactamase

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