Synergistic Activity of Cefiderocol in Combination with Avibactam, Sulbactam or Tazobactam against Carbapenem-Resistant Gram-Negative Bacteria.

Autor: Lewis RE; Department of Molecular Medicine, University of Padova, 35122 Padova, Italy., Palombo M; IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40135 Bologna, Italy., Diani E; Department of Diagnostic and Public Health, Microbiology Section, Verona University, 37134 Verona, Italy., Secci B; IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40135 Bologna, Italy., Gibellini D; Department of Diagnostic and Public Health, Microbiology Section, Verona University, 37134 Verona, Italy., Gaibani P; Department of Diagnostic and Public Health, Microbiology Section, Verona University, 37134 Verona, Italy.
Jazyk: angličtina
Zdroj: Cells [Cells] 2024 Aug 06; Vol. 13 (16). Date of Electronic Publication: 2024 Aug 06.
DOI: 10.3390/cells13161315
Abstrakt: We investigated the activity of cefiderocol/β-lactamase inhibitor combinations against clinical strains with different susceptibility profiles to cefiderocol to explore the potentiality of antibiotic combinations as a strategy to contain the major public health problem of multidrug-resistant (MDR) pathogens. Specifically, we evaluated the synergistic activity of cefiderocol with avibactam, sulbactam, or tazobactam on three of the most "Critical Priority" group of MDR bacteria (carbapenem-resistant Enterobacterales , Pseudomonas aeruginosa , and Acinetobacter baumannii ). Clinical isolates were genomically characterized by Illumina iSeq 100. The synergy test was conducted with time-kill curve assays. Specifically, cefiderocol/avibactam, /sulbactam, or /tazobactam combinations were analyzed. Synergism was assigned if bacterial grow reduction reached 2 log 10 CFU/mL. We reported the high antimicrobial activity of the cefiderocol/sulbactam combination against carbapenem-resistant Enterobacterales , P. aeruginosa , and A. baumannii ; of the cefiderocol/avibactam combination against carbapenem-resistant Enterobacterales ; and of the cefiderocol/tazobactam combination against carbapenem-resistant Enterobacterales and P. aeruginosa. Our results demonstrate that all β-lactamase inhibitors (BLIs) tested are able to enhance cefiderocol antimicrobial activity, also against cefiderocol-resistant isolates. The cefiderocol/sulbactam combination emerges as the most promising combination, proving to highly enhance cefiderocol activity in all the analyzed carbapenem-resistant Gram-negative isolates, whereas the Cefiderocol/tazobactam combination resulted in being active only against carbapenem-resistant Enterobacterales and P. aeruginosa, and cefiderocol/avibactam was only active against carbapenem-resistant Enterobacterales.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje