Multicenter, retrospective cohort study of antimycobacterial treatment-related harms among patients with non-tuberculosis <i>Mycobacterium</i> infections in the United States

Non-tuberculosis mycobacteria (NTM) are extensively drug-resistant organisms that require long-term therapy. The study purpose was to quantify the incidence of and risk factors for antimycobacterial-associated adverse drug events (ADEs) in persons with NTM infections receiving outpatient therapy. A multicenter, retrospective cohort was performed of persons with NTM infections who received antimycobacterial treatment from 2013 to 2024. Inclusion criteria were age ≥18 years, ≥1 month of outpatient treatment, and ≥1 follow-up outpatient visit within 3 months of index encounter. <i>Mycobacterium avium</i> complex and <i>Mycobacterium tuberculosis</i> complex were excluded. The primary outcome was development of pre-specified treatment-related ADE or acute kidney injury (AKI), thrombocytopenia, and/or <i>Clostridioides difficile</i> infection (CDI) through 12 months of therapy. Secondary outcomes included therapy discontinuation due to any treatment-related ADEs. Two hundred patients were included: 14% developed a pre-specified ADE. <i>Mycobacterium abscessus</i> (29%) was the most common pathogen; most initial regimens included a macrolide (54%), systemic aminoglycoside (24%), β-lactam (24%), or tetracycline derivative (22%). The most common pre-specified ADEs were thrombocytopenia (9%), AKI (8%), and CDI (<1%). The median (IQR) time-to-ADE was 25 (18-38) days from initial outpatient regimen; patients who received aminoglycoside- or oxazolidinone-based therapies were more likely to develop a pre-specified ADE (adjOR, 3.9; 95% CI, 1.7-9.2). Therapy discontinuation due to any ADE occurred in 35% of patients; the median (IQR) time-to-any ADE was 32 (21-58) days. ADEs in persons with NTM infections are common and occur near the first month of outpatient treatment. Intensified monitoring and/or use of more tolerable antimycobacterial regimens early in treatment may be an appropriate approach to avoid harms.Treatment of non-tuberculosis mycobacteria is complicated by adverse drug events (ADEs). This work quantified the incidence and time course of pre-determined, clinically relevant ADEs (acute kidney injury, thrombocytopenia, and <i>C. difficile</i> infection), which occurred in 14% of patients within 30 days of outpatient treatment.