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

被引：0

作者：

Lewis, Russell E. ^{[1
]}

Palombo, Marta ^{[2
]}

Diani, Erica ^{[3
]}

Secci, Benedetta ^{[2
]}

Gibellini, Davide ^{[3
]}

Gaibani, Paolo ^{[3
]}

机构：

[1] Univ Padua, Dept Mol Med, I-35122 Padua, Italy

[2] Univ Bologna, IRCCS Azienda Osped, I-40135 Bologna, Italy

[3] Verona Univ, Dept Diagnost & Publ Hlth, Microbiol Sect, I-37134 Verona, Italy

来源：

CELLS | 2024年 / 13卷 / 16期

关键词：

carbapenem-resistant Enterobacteriales; carbapenem-resistant Pseudomonas aeruginosa; carbapenem-resistant Acinetobacter baumannii; cefiderocol/avibactam; cefiderocol/sulbactam; cefiderocol/tazobactam;

D O I：

10.3390/cells13161315

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We investigated the activity of cefiderocol/beta-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 beta-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.

引用

页数：9