Mycobacterium tuberculosis sterilizing activity of faropenem, pyrazinamide and linezolid combination and failure to shorten the therapy duration.
Int J Infect Dis
; 104: 680-684, 2021 Mar.
Article
em En
| MEDLINE
| ID: mdl-33556616
ABSTRACT
BACKGROUND:
Faropenem (F), an orally bioavailable ß-lactam, kills Mycobacterium tuberculosis (Mtb) without the help of a ß-lactamase inhibitor. This study explored the sterilizing effect of adding F once or twice daily to a linezolid (L) plus pyrazinamide (Z) backbone regimen.METHODS:
In vitro studies were performed using the hollow fiber model of tuberculosis (HFS-TB) to compare the kill rates of 1) ZL two-drug combination; 2) F administered once daily plus ZL (F1ZL); 3) F administered twice-daily plus once daily ZL (F2ZL); 4) F2ZL with high-dose Z (F2ZhiL); 5) standard therapy of isoniazid, rifampin and Z; and 6) non-treated controls. The study was performed over 56 days with three HFS-TB replicates for each regimen.RESULTS:
Mtb in the non-treated HFS-TB grew at a rate of 0.018 ± 0.007 log10 CFU/mL/day. The exponential kill rates for standard therapy were 6.6-13.2-fold higher than ZL dual therapy. The F1ZL and F2ZL regimens ranked third. The pre-existing isoniazid-resistant sub-population in the inoculum (1.34 ± 0.57 log10 CFU/mL) grew to 4.21 ± 0.58 log10 CFU/mL in 56 days in non-treated HFS-TB. However, no isoniazid-resistant sub-population was recorded in any of the FZL combination regimens.CONCLUSION:
Due to the slow kill rate compared to standard therapy, FZL regimens are unlikely to shorten therapy duration. Efficacy of these regimens against drug-resistant tuberculosis needs to be determined.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazinamida
/
Tuberculose
/
Beta-Lactamas
/
Linezolida
/
Mycobacterium tuberculosis
/
Antituberculosos
Limite:
Humans
Idioma:
En
Revista:
Int J Infect Dis
Assunto da revista:
DOENCAS TRANSMISSIVEIS
Ano de publicação:
2021
Tipo de documento:
Article