Trimethoprim/sulfamethoxazole pharmacodynamics against Stenotrophomonas maltophilia in the in vitro chemostat model.
J Antimicrob Chemother
; 77(11): 3187-3193, 2022 10 28.
Article
en En
| MEDLINE
| ID: mdl-36101486
ABSTRACT
BACKGROUND:
Trimethoprim/sulfamethoxazole has historically been the treatment of choice for infection caused by Stenotrophomonas maltophilia. This study sought to define the pharmacodynamic indices and magnitude of exposure required for stasis and 1â log10â cfu reductions.METHODS:
Pharmacodynamic studies were conducted using the in vitro chemostat model over 24â h against three trimethoprim/sulfamethoxazole-susceptible S. maltophilia isolates with MICs from 0.25/4.75 to 2/38â mg/L. The primary endpoint was the change in cfu at 24â h relative to baseline. The log ratio of the area under the cfu curve (LR AUcfu) was a secondary endpoint. Trimethoprim and sulfamethoxazole exposures required for stasis and 1â log10â cfu/mL reduction were determined.RESULTS:
Trimethoprim/sulfamethoxazole exposures achieved stasis and 1â log10â cfu/mL reductions in 9/16 (56%) and 2/16 (13%) of experiments. Both the fAUC/MIC and fCmax/MIC were identified as equivalent pharmacodynamic drivers, with stasis achieved at an fAUC/MIC of 67.4 and 30.0 for trimethoprim and sulfamethoxazole, respectively. Clinically meaningful exposures required to achieve 1â log10â cfu/mL reductions were not quantifiable. The LR AUcfu analysis supported the lack of overall bacterial burden reduction against S. maltophilia.CONCLUSIONS:
In this in vitro chemostat model, trimethoprim/sulfamethoxazole monotherapy, even at higher doses, achieved limited activity against susceptible S. maltophilia.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Infecciones por Bacterias Gramnegativas
/
Stenotrophomonas maltophilia
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos