The risk of drug resistance during long-acting antimicrobial therapy

• DOI: 10.1098/rspb.2022.1444
• Publication Date: 2022-11-09T14:31:11Z
• Authors: Anjalika Nande; Alison L. Hill
• Keywords: 0303 health sciences; 03 medical and health sciences; Anti-Infective Agents; Drug Resistance, Viral; Humans; Tuberculosis; HIV Infections; Biological Applications; 3. Good health

The emergence of drug resistance during antimicrobial therapy is a major global health problem, especially for chronic infections like human immunodeficiency virus, hepatitis B and C, tuberculosis. Sub-optimal adherence to long-term treatment an important contributor risk. New long-acting drugs are being developed weekly, monthly or less frequent dosing improve adherence, but may lead exposure intermediate levels. In this study, we analyse the effect frequency on risk evolving time-varying We find that therapies can increase, decrease have little resistance, depending source (pre-existing de novo) degree rates absorption clearance. Long-acting with rapid absorption, slow clearance strong wild-type inhibition tend reduce caused by partially resistant strains in early stages even if they do not adherence. However, subpopulations microbes persist reactivate sub-optimal treatment, longer-acting substantially increase Our results show kinetics affect selection complicated manner, pathogen-specific models needed evaluate benefits new therapies.