Dose-fractionation of moxifloxacin for the treatment of tuberculosis: impact of dosing interval and elimination half-life on microbial kill and resistance suppression.

We examined 12, 24 and 48 hr dosing intervals with doses of 200 mg, 400 mg and 800 mg for each interval, respectively. Within each interval, we had an arm where half-lives of 12, 8 and 4 hr were simulated. We attempted to keep the CAvg (AUC) constant across arms. We found that susceptible bacterial load decline was linked to CAvg, as we had indicated previously. Resistance suppression, a non-monotonic function, had CMin as the linked index. The 48 hr interval with the 4 hr half-life had the largest less-susceptible population. Balancing bacterial kill, resistance suppression, toxicity (CPeak-linked) and adherence, we conclude that the 400 mg dose daily is optimal for moxifloxacin.
PMID: 33468465 [PubMed - as supplied by publisher]

Source: Antimicrobial Agents and Chemotherapy - January 19, 2021 Category: Microbiology Authors: Drusano GL, Rogers S, Brown D, Peloquin CA, Neely M, Yamada W, Kim S, Almoslem M, Schmidt S, Louie A Tags: Antimicrob Agents Chemother Source Type: research