In vitro efficacy of imipenem-relebactam and cefepime-AAI101 against a global collection of ESBL-positive and carbapenemase-producing Enterobacteriaceae.
Int J Antimicrob Agents
; 56(1): 105925, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32084512
ABSTRACT
OBJECTIVES:
To evaluate the potential clinical in vitro efficacy of novel ß-lactam/ß-lactamase-inhibitor combinations - including imipenem-relebactam (IPM-REL) and cefepime-AAI101 (enmetazobactam) (FEP-AAI) - against contemporary multidrug-resistant (MDR) Enterobacteriaceae.METHODS:
Agar-based MIC screening against MDR Enterobacteriaceae (n = 264) was used to evaluate the in vitro efficacy of IPM-REL and FEP-AAI, to compare the results with established combinations, and to investigate alternative ß-lactam partners for relebactam (REL) and enmetazobactam (AAI). The inhibition activities of REL, AAI and the comparators avibactam (AVI) and tazobactam, against isolated recombinant ß-lactamases covering representatives from all four Ambler classes of ß-lactamases, were tested using a fluorescence-based assay.RESULTS:
Using recombinant proteins, all four inhibitors were highly active against the tested class A serine ß-lactamases (SBLs). REL and AVI showed moderate activity against the Class C AmpC from Pseudomonas aeruginosa and the Class D OXA-10/-48 SBLs, but outperformed tazobactam and AAI. All tested inhibitors lacked activity against Class B metallo-ß-lactamases (MBLs). In the presence of REL and IPM, but not AAI, susceptibility increased against Klebsiella pnuemoniae carbapenemase (KPC)-positive and OXA-48-positive isolates. Both aztreonam-AVI and ceftolozane-tazobactam were more effective than IPM-REL. In all the tested combinations, AAI was a more effective inhibitor of class A ß-lactamases (ESBLs) than the established inhibitors.CONCLUSION:
The results lead to the proposal of alternative combination therapies involving REL and AAI to potentiate the use of ß-lactams against clinical Gram-negative isolates expressing a variety of lactamases. They highlight the potential of novel combinations for combating strains not covered by existing therapies.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Inibidores de beta-Lactamases
/
Enterobacteriáceas Resistentes a Carbapenêmicos
/
Antibacterianos
Tipo de estudo:
Evaluation_studies
Limite:
Humans
Idioma:
En
Revista:
Int J Antimicrob Agents
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido