Thioridazine Is an Efflux Pump Inhibitor in Mycobacterium avium Complex but of Limited Clinical Relevance

Abstract

Treatment of <i>Mycobacterium avium</i> complex pulmonary disease (MAC-PD) is challenging partly due to high efflux pump expression. Thioridazine might block these efflux pumps. We explore the efficacy of thioridazine against <i>M. avium</i> isolates using MICs, time-kill combination assays, <i>ex vivo</i> macrophage infection assays, and efflux assays. Thioridazine is bactericidal against <i>M. avium</i>, inhibits intracellular growth at 2× MIC, and blocks ethidium bromide efflux. However, its toxicity and low plasma concentrations make it unlikely to add efficacy to MAC-PD therapy.