Clofazimine-Containing Regimen Shown to Safely, Effectively Treat Rapidly Growing Mycobacteria Infections

A clofazimine (CFZ)-containing regimen was found to be well tolerated and potentially effective in patients with rapidly growing mycobacteria (RGM) infection, especially nonpulmonary and non—Mycobacterium abscessus complex (MAbsC) infections, according to findings of a retrospective cohort study published this week in the journal Open Forum Infectious Diseases.

RGM, a subset of nontuberculous bacteria, are associated with high rates of natural antibiotic resistance, which requires prolonged antibiotic therapies associated with heightened toxicity exposure. Researchers sought to expand on the limited therapies available for these types of infections by seeking a therapy that was less toxic and more effective for patients. CFZ, a riminophenazine antibiotic, was noted by researchers for its promising in vitro activity in RGM, but its limited clinical data in RGM warranted further investigation.

Researchers conducted a 6-year retrospective cohort study of 55 patients treated for RGM infection with a CFZ-containing regimen in the University of Pennsylvania Health System. Analyses, which occurred from January 1, 2010, to December 31, 2016, included a primary outcome measurement of clinical cure, defined as no evidence of clinical or microbiologic infection recurrence after 1 year following treatment completion, as well as, several secondary outcomes:

• Treatments conducted during the study period were provided in combination with a median of 5 other antibiotic agents during each treatment course
• Secondary outcomes included clinical, radiologic, and microbiologic response; all-cause mortality; infection-specific mortality; and treatment-related adverse events
• Descriptive and unadjusted analyses performed to delineate associations between pertinent demographic and comorbidity data, clinical presentation, treatment history, and treatment outcomes

Of the 55 patients, 28 (51%) had isolated pulmonary disease, 4 (7%) had pulmonary and disseminated disease, and 23 (42%) had isolated nonpulmonary disease. Study results showed that for patients with pulmonary infection, 43% achieved clinical cure with initial treatment regimen, while patients with nonpulmonary infection exhibited a stark 71% clinical cure rate. CFZ was found to be well tolerated among the cohort and was discontinued prematurely in 20% of patients, in the context of discontinuing all antibiotic agents, noted the authors.

“For the first time, we demonstrate that therapy with CFZ-containing regimens can result in durable clinical cure after 12 months of post-treatment follow-up,” said the authors.

While CFZ was shown to potentially benefit patients with RGM infections, the authors listed several limitations to the study. Patients were treated with multiple antibiotics in addition to CFZ so it was not possible to determine which antibiotics were effective as part of the regimen. Outcomes were additionally derived from patients who completed therapy, which may leave out a section of patients who could have developed treatment failure. The relatively small sample size and lack of placebo control also warrants further analyses of this demographic.

“CFZ may be an effective component of treatment regimens for RGM infections in achieving durable clinical cures, specifically for cutaneous infections and in non-MAbsC infections,” said the authors.

Reference

Carey GB, Tebas P, Vinnard C, et al. Clinical outcomes of clofazimine use for rapidly growing mycobacterial infections [published online October 21, 2019]. Open Forum Infect Dis. doi: 10.1093/ofid/ofz456.