Clofazimine for treatment of multidrug-resistant non-tuberculous mycobacteria

Background:/Question: Nontuberculous mycobacteria (NTM) infections are increasingly detected but difficult to cure given complex drug-resistance patterns. Select U. S. centers have incorporated clofazimine in the treatment of NTM but experience is limited as procurement restrictions hamper widespread use. Methods: A prospective cohort study was performed in patients diagnosed with pulmonary or extrapulmonary NTM infection and treated with clofazimine between February 2015 and April 2019 at a tertiary referral hospital. Treatment success was defined by a combined outcome of clinical stabilization, microbiologic cure and radiologic improvement. Secondary outcomes included all-cause mortality and time to sputum culture conversion. Uni/multi-variate regression were used to define associations between pre-determined predictor variables and overall treatment outcome. Results: Of 44 patients enrolled, 39 (89 %) received clofazimine along with a median of 3 concomitant antibiotics. Thirty-one (80 %) of patients had pulmonary NTM infection, with Mycobacterium abscessus group and Mycobacterium avium complex being the most common species groups identified. Of 36 people with evaluable outcomes, 35 (97 %) survived and 22 (58 %) had treatment success, including 12 of 19 (63 %) with Mycobacterium abscessus group. In multivariate analysis, patients with Mycobacterium abscessus group were more likely to experience treatment success (OR 18.22, 95%CI 0.972-341.43, p = 0.052), while macmlide resistance predicted a lack of treatment success (OR 0.053, 95%CI 0.003-0.841, p = 0.037). Clofazimine was well-tolerated. Conclusion: Adding clofazimine to multi-class antibiotic regimens for drug-resistant NTM infection led to treatment success in the majority treated. Randomized controlled studies are needed to determine the individual impact of clofazimine within an otherwise optimized drug regimen.

Automated summary

Incorporating clofazimine into the treatment of NTM infections showed promising treatment success rates, especially for patients with Mycobacterium abscessus group. However, drug resistance remains a key factor affecting treatment outcomes.