Sitafloxacin pharmacokinetics/pharmacodynamics against multidrug-resistant bacteria in a dynamic urinary tract infection in vitro model.
J Antimicrob Chemother
; 78(1): 141-149, 2022 12 23.
Article
en En
| MEDLINE
| ID: mdl-36329646
ABSTRACT
OBJECTIVES:
Sitafloxacin is one of the newer generation fluoroquinolones with highly active against multidrug-resistant (MDR) bacteria. Our objectives were to identify the sitafloxacin pharmacokinetic/pharmacodynamic (PK/PD) index and breakpoints against MDR isolate in the urinary tract infection model.METHODS:
Forty-eight MDR isolates underwent sitafloxacin and levofloxacin microdilution susceptibility testing. A 24â h in vitro model was established that simulated the healthy subjects urodynamics of sitafloxacin fumarate injection. Ten MDR isolates (four carbapenem-resistant Escherichia coli, three carbapenem-resistant P. aeruginosa and three vancomycin-resistant E. faecium) were selected. The drug efficacy was quantified by the change in log colony counts within 24â h. A sigmoid Emax model was fitted to the killing effect data. Monte Carlo simulations were performed to assess target attainment for the sitafloxacin fumarate doses of 100 and 200â mg q24h.RESULTS:
Analysis indicated that the MICs of sitafloxacin were all significantly lower than that of levofloxacin (Pâ<â0.01). The UAUC0-24h/MIC targets required to achieve stasis, 1-log10 killing and 2-log10 killing were 63.60, 79.49 and 99.45 (carbapenem-resistant E. coli), 60.85, 90.31 and 128.95 (carbapenem-resistant P. aeruginosa), 65.91, 77.81 and 103.11 (vancomycin-resistant E. faecium). Monte Carlo simulation showed the infusion of sitafloxacin fumarate 100â mg q24h was able to achieve 90% probability of target attainment against bacteria with MIC of 8â mg/L for the common complicated urinary tract infections.CONCLUSIONS:
Sitafloxacin fumarate injection is an alternative therapeutic agent for the treatment of UTIs caused by MDR isolates.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_neglected_diseases
/
3_zoonosis
Asunto principal:
Infecciones Urinarias
/
Antibacterianos
Límite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2022
Tipo del documento:
Article
País de afiliación:
China