In-vitro activity of the novel β-lactam/β-lactamase inhibitor combinations and cefiderocol against carbapenem-resistant Pseudomonas spp. clinical isolates collected in Switzerland in 2022

Abstract

To evaluate the in-vitro activity of the novel commercially-available drugs, including meropenem-vaborbactam (MEV), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam (IPR) as well as cefiderocol (FDC), against carbapenem-resistant Pseudomonas spp. (CRP) isolates. All CRP isolates collected at the Swiss National Reference Laboratory (NARA) over the year 2022 (n = 170) have been included. Most of these isolates (n = 121) were non-carbapenemase producers. Among the 49 carbapenemase producers, 47 isolates produced metallo-β-lactamases (MBL) including NDM-1 (n = 11), VIM-like (n = 28), IMP-like (n = 7), and both NDM-1 and VIM-2 (n = 1) and two isolates produced the class A carbapenemase GES-5. Susceptibility testing was determined by broth microdilution method (BMD), or disk diffusion test, and results interpreted following EUCAST guidelines. The susceptibility rates for MEV, CZA, C/T and IPR were found to be 41%, 45%, 59% and 58%, respectively, for the whole set of isolates tested. Among non-carbapenemase producers, susceptibility rates for these β-lactam/β-lactamase inhibitors (BL/BLI) combinations were higher, determined at 55%, 61%, 83%, and 82%, respectively. The overall susceptibility of carbapenemase-producing Pseudomonas spp. to novel BL/BLI was relatively low, while 80% of these isolates demonstrated susceptibility to FDC, with a similar proportion (79%) observed among MBL producers. A total of 10 MBL-producing isolates (6%), mainly NDM-1, were found to exhibit resistance to all drugs tested, with the exception of colistin. FDC exhibited an excellent in-vitro activity against this collection of CRP recovered from Switzerland in 2022, including MBL producers. The new BL/BLI combinations displayed significant activity against non-carbapenemase CRP, with IPR and C/T showing the highest susceptibility rates.

Keywords: Avibactam; Carbapenemase; Cefiderocol; Ceftolozane; Imipenem; Meropenem; Relebactam; Vaborbactam; Β-lactamase.