Assessing the in vivo efficacy of rational antibiotics and combinations against difficult-to-treat Pseudomonas aeruginosa producing GES ß-lactamases.
J Antimicrob Chemother
; 78(8): 1843-1847, 2023 08 02.
Article
em En
| MEDLINE
| ID: mdl-37357368
ABSTRACT
OBJECTIVES:
We evaluated the in vivo efficacy of human-simulated regimens (HSRs) of cefiderocol, ceftazidime/avibactam, meropenem and ceftazidime/avibactam/meropenem combination against Guiana-extended spectrum (GES)-producing Pseudomonas aeruginosa isolates.METHODS:
Eighteen P. aeruginosa isolates producing GES-1 (nâ=â5), GES-5 (nâ=â5) or miscellaneous GESs (combinations of GES-19, GES-20 and/or GES-26; nâ=â8) were evaluated. In vitro MIC testing was determined using broth microdilution. In a validated murine thigh infection model, HSRs of cefiderocol 2 g q8h as a 3 h IV infusion, ceftazidime/avibactam 2.5 g q8h as a 2 h IV infusion, meropenem 2 g q8h as a 3 h IV infusion or ceftazidime/avibactam/meropenem were administered. Change in bacterial burden relative to baseline and the proportion of isolates in each genotypic group meeting 1-log10 kill endpoint were assessed.RESULTS:
Modal MICs (mg/L) ranged from 0.125 to 1 for cefiderocol, 4 to >64 for ceftazidime/avibactam and 2 to >64 for meropenem. Cefiderocol produced >1-log10 of kill against all 18 tested isolates. Meropenem was active against all GES-1 isolates whereas activity against GES-5 and miscellaneous GESs was lacking, consistent with the MICs. Ceftazidime/avibactam was active against all GES-1 and GES-5 isolates and retained activity against 62.5% of miscellaneous GESs including isolates with elevated MICs. For isolates where ceftazidime/avibactam failed, the addition of meropenem restored the in vivo efficacy.CONCLUSIONS:
As monotherapy, cefiderocol was active in vivo against all tested isolates. The activities of meropenem or ceftazidime/avibactam alone were variable; however, a combination of both was active against all isolates. Cefiderocol and ceftazidime/avibactam/meropenem could be valuable therapeutic options for GES-producing P. aeruginosa infections. Clinical confirmatory data are warranted.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ceftazidima
/
Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos