Thioridazine Is an Efflux Pump Inhibitor in Mycobacterium avium Complex but of Limited Clinical Relevance.
Ruth MM., Pennings LJ., Koeken VACM., Schildkraut JA., Hashemi A., Wertheim HFL., Hoefsloot W., van Ingen J.
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 assays, and efflux assays. Thioridazine is bactericidal against M. avium, 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.