Evaluation of Antimicrobial Effects of a New Polymyxin Molecule (SPR741) When Tested in Combination with a Series of ß-Lactam Agents Against a Challenge Set of Gram-Negative Pathogens.
Microb Drug Resist
; 26(4): 319-328, 2020 Apr.
Article
em En
| MEDLINE
| ID: mdl-31596663
ABSTRACT
The antimicrobial activities of several ß-lactam agents were tested by broth microdilution alone and in combination with a new polymyxin analog, SPR741 (at a fixed concentration of 8 mg/L), against a challenge set of clinical isolates (202 Escherichia coli and 221 Klebsiella pneumoniae isolates). Using Clinical and Laboratory Standards Institute (CLSI) or European Committee on Antimicrobial Susceptibility Testing (EUCAST) susceptibility criteria for each partner antibiotic, mecillinam-SPR741, temocillin-SPR741, and piperacillin-tazobactam-SPR741 combinations had susceptibility rates higher (85.6-100.0%) than the respective agents tested alone (47.5-88.7%) against extended-spectrum ß-lactamase (ESBL)-producing E. coli and K. pneumoniae. Temocillin-SPR741 (97.8% susceptible) had MIC50 (minimum inhibitory concentration) and MIC90 results of 0.5 and 2 mg/L, respectively, against K. pneumoniae carbapenemase (KPC)-producing E. coli, 8- to 16-fold lower than temocillin alone (MIC50/90, 8/16 mg/L; 65.2% susceptible). The mecillinam MIC50/MIC90 results dropped to 1/4 mg/L (from 128/>256 mg/L when tested alone) against metallo-ß-lactamase (MBL)-producing E. coli. These MICs for mecillinam-SPR741 resulted in a susceptibility rate of 96.9% versus 9.4% for mecillinam. In general, a decrease in MICs for ß-lactams (MIC90, >32 mg/L) in the presence of SPR741 was not observed against KPC-, MBL- or OXA-48-like-producing K. pneumoniae. These study results indicate that some agents had a significant increase in in vitro activity in the presence of SPR741 and could become potential strategic options for treating serious infections caused by multidrug-resistant Enterobacteriaceae.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
3_ND
Problema de saúde:
3_neglected_diseases
/
3_zoonosis
Assunto principal:
Polimixinas
/
Peptídeos Catiônicos Antimicrobianos
/
Beta-Lactamas
/
Escherichia coli
/
Klebsiella pneumoniae
/
Antibacterianos
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Revista:
Microb Drug Resist
Assunto da revista:
MICROBIOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2020
Tipo de documento:
Article