Preserved Efficacy and Reduced Toxicity with Intermittent Linezolid Dosing in Combination with Bedaquiline and Pretomanid in a Murine Tuberculosis Model.

ABSTRACT: The novel regimen of bedaquiline, pretomanid, and linezolid (BPaL) is highly effective against drug-resistant tuberculosis, but linezolid toxicities are frequent. We hypothesized that, for a similar total weekly cumulative dose, thrice-weekly administration of linezolid would preserve efficacy while reducing toxicity compared with daily dosing, in the context of the BPaL regimen. Using C3HeB/FeJ and BALB/c mouse models of tuberculosis disease, thrice-weekly linezolid dosing was compared with daily dosing, with intermittent dosing introduced (i) from treatment initiation or (ii) after an initial period of daily dosing. In all animals, BPa was dosed daily throughout treatment. Blood counts were used to assess hematologic toxicity. After unexpected findings of apparent antagonism, we conducte

SUBMITTER: Bigelow KM 

PROVIDER: S-EPMC7508620 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature