Trimethoprim/sulfamethoxazole pharmacodynamics against Stenotrophomonas maltophilia in the in vitro chemostat model.

Autor:	Lasko MJ; Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA., Tabor-Rennie JL; Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA., Nicolau DP; Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.; Division of Infectious Diseases, Hartford Hospital, Hartford, CT, USA., Kuti JL; Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2022 Oct 28; Vol. 77 (11), pp. 3187-3193.
DOI:	10.1093/jac/dkac304
Abstrakt:	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 1 log10 cfu reductions. Methods: Pharmacodynamic studies were conducted using the in vitro chemostat model over 24 h against three trimethoprim/sulfamethoxazole-susceptible S. maltophilia isolates with MICs from 0.25/4.75 to 2/38 mg/L. The primary endpoint was the change in cfu at 24 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 1 log10 cfu/mL reduction were determined. Results: Trimethoprim/sulfamethoxazole exposures achieved stasis and 1 log10 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 1 log10 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. (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu