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Mycobacterium avium complex (MAC) bacteria, the most common cause of nontuberculous mycobacterial pulmonary disease, also represent frequent opportunistic pathogens in immunocompromised individuals. MAC therapy consists of azithromycin (AZM), ethambutol (ETB), and rifampicin (RIF) for 12 months after sputum culture conversion. However, as a potent CYP3A4 inducer, RIF hinders the achievement of adequate AZM concentrations. Investigators used a hollow-fiber model with M. avium–infected THP-1 monocytes to simulate epithelial pharmacokinetics of AZM and ETB with or without RIF over a 21-day course. Bacterial load and THP-1 cell density were monitored, bacterial adaptation to drug exposure was assessed with RNA sequencing, and emergence of AZM r…