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

Treatment of Mycobacterium avium 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 M. avium isolates using MICs, time-kill combination assays, ex vivo macrophage infection as- says, and efflux assays. Thioridazine is bactericidal against M. avium , inhibits intracellular growth at 2X MIC, and blocks ethidium bromide efflux. However, its toxicity and low plasma concentrations make it unlikely to add efficacy to MAC-PD therapy.