Multidrug-resistant Gram-negative clinical isolates with reduced susceptibility/resistance to cefiderocol: which are the best present and future therapeutic alternatives?

被引:9
作者
Le Terrier, Christophe [1 ,2 ]
Freire, Samanta [1 ]
Nordmann, Patrice [1 ,3 ]
Poirel, Laurent [1 ,3 ]
机构
[1] Univ Fribourg, Dept Med, Emerging Antibiot Resistance Unit, Med & Mol Microbiol, Chemin Musee 18, CH-1700 Fribourg, Switzerland
[2] Univ Hosp Geneva, Div Intens Care Unit, Geneva, Switzerland
[3] Swiss Natl Reference Ctr Emerging Antibiot Resist, Fribourg, Switzerland
关键词
Cefiderocol; Taniborbactam; Avibactam; Nacubactam; Zidebactam; Relebactam; Vaborbactam; beta-Lactamase; PSEUDOMONAS-AERUGINOSA; EXTENDED-SPECTRUM; AMPC; ENTEROBACTERALES;
D O I
10.1007/s10096-023-04732-4
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Purpose To evaluate the different present and future therapeutic beta-lactam/beta-lactamase inhibitor (BL/BLI) alternatives, namely aztreonam-avibactam, imipenem-relebactam, meropenem-vaborbactam, cefepime-zidebactam, cefepime-taniborbactam, meropenem-nacubactam, and sulbactam-durlobactam against clinical isolates showing reduced susceptibility or resistance to cefiderocol in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa.Methods MIC values of aztreonam, aztreonam-avibactam, cefepime, cefepime-taniborbactam, cefepime-zidebactam, imipenem, imipenem-relebactam, meropenem, meropenem-vaborbactam, meropenem-nacubactam, sulbactam-durlobactam, and cefiderocol combined with a BLI were determined for 67, 9, and 11 clinical Enterobacterales, P. aeruginosa or A. baumannii isolates, respectively, showing MIC values of cefiderocol being >= 1 mg/L. If unavailable, the respective beta-lactam breakpoints according to EUCAST were used for BL/BLI combinations.Results For Enterobacterales, the susceptibility rates for aztreonam, cefepime, imipenem, and meropenem were 7.5%, 0%, 10.4%, and 10.4%, respectively, while they were much higher for cefepime-zidebactam (91%), cefiderocol-zidebactam (91%), meropenem-nacubactam (71.6%), cefiderocol-nacubactam (74.6%), and cefiderocol-taniborbactam (76.1%), as expected. For P. aeruginosa isolates, the higher susceptibility rates were observed for imipenem-relebactam, cefiderocol-zidebactam, and meropenem-vaborbactam (56% for all combinations). For A. baumannii isolates, lower susceptibility rates were observed with commercially or under development BL/BLI combos; however, a high susceptibility rate (70%) was found for sulbactam-durlobactam and when cefiderocol was associated to some BLIs.Conclusions Zidebactam- and nacubactam-containing combinations showed a significant in vitro activity against multidrug-resistant Enterobacterales clinical isolates with reduced susceptibility to cefiderocol. On the other hand, imipenem-relebactam and meropenem-vaborbactam showed the highest susceptibility rates against P. aeruginosa isolates. Finally, sulbactam-durlobactam and cefiderocol combined with a BLI were the only effective options against A. baumannii tested isolates.
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页码:339 / 354
页数:16
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