Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa

Authors

Robbie R. Haines
Papanin Putsathit, Edith Cowan UniversityFollow
Katherine A. Hammer
Anna S. Tai

Document Type

Journal Article

Publication Title

Scientific Reports

Volume

12

Issue

1

PubMed ID

36207358

Publisher

Nature

School

School of Medical and Health Sciences

RAS ID

51779

Funders

Conquer Cystic Fibrosis Research Grant from Conquer Cystic Fibrosis

Comments

Haines, R. R., Putsathit, P., Hammer, K. A., & Tai, A. S. (2022). Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa. Scientific reports, 12, Article 16814. https://doi.org/10.1038/s41598-022-21101-x

Abstract

Multidrug resistant (MDR) P. aeruginosa accounts for 35 % of all P. aeruginosa isolated from respiratory samples of patients with cystic fibrosis (CF). The usefulness of β-lactam antibiotics for treating CF, such as carbapenems and later generation cephalosporins, is limited by the development of antibacterial resistance. A proven treatment approach is the combination of a β-lactam antibiotic with a β-lactamase inhibitor. New β-lactam/β-lactamase inhibitor combinations are available, but data are lacking regarding the susceptibility of MDR CF-associated P. aeruginosa (CFPA) to these new combination therapies. In this study we determined MIC values for three new combinations; imipenem-relebactam (I-R), ceftazidime-avibactam (CZA), and ceftolozane-tazobactam (C/T) against MDR CFPA (n = 20). The MIC90 of I-R, CZA, and C/T was 64/4, 32/4, and 16/8 (all µg/mL), respectively. The susceptibility of isolates to imipenem was not significantly improved with the addition of relebactam (p = 0.68). However, susceptibility to ceftazidime was significantly improved with the addition of avibactam (p < 0.01), and the susceptibility to C/T was improved compared to piperacillin/tazobactam (p < 0.05) These data provide in vitro evidence that I-R may not be any more effective than imipenem monotherapy against MDR CFPA. The pattern of susceptibility observed for CZA and C/T in the current study was similar to data previously reported for non-CF-associated MDR P. aeruginosa.

DOI

10.1038/s41598-022-21101-x

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