Both Pharmacokinetic Variability and Granuloma Heterogeneity Impact the Ability of the First-Line Antibiotics to Sterilize Tuberculosis Granulomas.

ABSTRACT: Tuberculosis (TB) remains as one of the world's deadliest infectious diseases despite the use of standardized antibiotic therapies. Recommended therapy for drug-susceptible TB is up to 6 months of antibiotics. Factors that contribute to lengthy regimens include antibiotic underexposure in lesions due to poor pharmacokinetics (PK) and complex granuloma compositions, but it is difficult to quantify how individual antibiotics are affected by these factors and to what extent these impact treatments. We use our next-generation multi-scale computational model to simulate granuloma formation and function together with antibiotic pharmacokinetics and pharmacodynamics, allowing us to predict conditions leading to granuloma sterilization. In this work, we focus on how PK variability, determined from

SUBMITTER: Cicchese JM 

PROVIDER: S-EPMC7105635 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature