Preserved Efficacy and Reduced Toxicity with Intermittent Linezolid Dosing in Combination with Bedaquiline and Pretomanid in a Murine Tuberculosis Model
Kristina M. Bigelow, Rokeya Tasneen, Yong S. Chang, Kelly E. Dooley, Eric L. Nuermberger
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.
Topics & Concepts
LinezolidDosingBedaquilineMedicineRegimenContext (archaeology)PharmacologyToxicityTuberculosisInternal medicineMycobacterium tuberculosisBiologyPathologyVancomycinStaphylococcus aureusGeneticsBacteriaPaleontologyTuberculosis Research and EpidemiologyAntimicrobial Resistance in StaphylococcusInfectious Diseases and Tuberculosis