2. Academic Validation
  3. Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa

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

  • Sci Rep. 2022 Oct 7;12(1):16814. doi: 10.1038/s41598-022-21101-x.
Robbie R Haines 1,  Papanin Putsathit 2,  Katherine A Hammer 3,  Anna S Tai 4 5 6
Affiliations

Affiliations

  • 1 School of Biomedical Sciences, The University of Western Australia, 30 Stirling Hwy, Crawley, Perth, WA, 6009, Australia. robbie.haines@uwa.edu.au.
  • 2 School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
  • 3 School of Biomedical Sciences, The University of Western Australia, 30 Stirling Hwy, Crawley, Perth, WA, 6009, Australia.
  • 4 Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
  • 5 Institute of Respiratory Health, Nedlands, WA, Australia.
  • 6 Medical School, The University of Western Australia, Perth, WA, Australia.
PMID: 36207358 DOI: 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.

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