Clofazimine Beneficial in Treating Drug-Resistant Nontuberculous Mycobacteria

Mycobacterium avium-intracellulare, MAI, non-tuberculous mycrobacteria which cause opportunistic infections in HIV-infected patients, 3D illustration
Clofazimine, previously used for drug-resistant TB, may help stem the increase in morbidity and mortality from nontuberculous mycobacteria infections.

Adding clofazimine (CFZ) to multiclass antibiotic regimens is beneficial in treating patients with drug-resistant nontuberculous mycobacteria (NTM) infection, according to study results published Pulmonary Pharmacology & Therapeutics

A prospective, observational cohort study was conducted among patients treated for an NTM infection with a CFZ-containing antibiotic regimen between February 2, 2015, and April 26, 2019, at a tertiary referral hospital. Results of the

The investigators evaluated success among the patients treated with a CFZ-containing antibiotic regimen through a prospective, observational cohort study of 44 hospital patients treated with this regimen for an NTM infection between February 2015 and April 2019. Successful treatment was defined by a combined outcome of clinical stabilization, microbiologic cure, and radiologic improvement. Secondary study outcomes included all-cause mortality and time to sputum culture conversion. Demographic, microbiologic, radiologic, clinical, and outcomes data were obtained at baseline and at periodic follow-up intervals.

Among the 44 enrolled patients, 39 were treated with CFZ along with a median of 3 concomitant antibiotics. The average age of the treated patients was 48 years (range, 15 to 83 years). Of these patients, 38 had at least 1 documented culture that showed NTM growth prior to the initiation of CFZ and 1 patient had a presumed cerebral NTM infection in which tissue sampling was unavailable for culture. Among the 33 participants with chronic lung disease, 15 had cystic fibrosis. Overall, 29 patients had a previously treated NTM infection and had received a median of 1.5 treatment trial regimens (range, 1 to 6 trials) prior to being prescribed a CFZ-containing antibiotic regimen. Further, 2 patients had received CFZ earlier, as part of a prior treatment regimen.

A total of 31 patients had pulmonary NTM infection, with Mycobacterium abscessus group and Mycobacterium avium complex the most common groups of species that were identified. Among 36 participants with evaluable outcomes, 35 survived and 22 attained treatment success, which included 63% (12 of 19) of those in the Mycobacterium abscessus group.

Per multivariate analysis, individuals with Mycobacterium abscessus were more likely to achieve treatment success (odds ratio [OR], 18.22; 95% CI, 0.972–341.43; P =.052), whereas macrolide resistance was significantly predictive of a lack of treatment success (OR, 0.053; 95% CI, 0.003–0.841; P =.037). CFZ was generally well tolerated among the patients, with 15 reporting potential side effects. The most common adverse events included gastrointestinal upset in 12 patients and skin pigmentation in 6 individuals.

The investigators concluded that CFZ is an important, well-tolerated drug in an otherwise scarce armamentarium for the treatment of drug-resistant NTM. Study findings are suggestive of the ongoing need to improve the availability of CFZ and to ease restrictions in procurement of the drug. Species-specific randomized controlled trials of NTM are warranted, in order to determine the individual impact of CFZ and other novel, repurposed treatments.

Disclosure: None of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies.


Pfaeffle HOI, Alameer RM, Marshall MH, Houpt ER, Albon DP, Heysell SK. Clofazimine for treatment of multidrug-resistant non-tuberculous mycobacteria. Pulm Pharmacol Ther. Published online July 20, 2021. doi:10.1016/j.pupt.2021.102058