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Clofazimine-containing regimen effectively treats rapidly growing mycobacteria infections
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Findings from a retrospective cohort study showed that a clofazimine-containing regimen was safe and effective at treating rapidly growing mycobacteria, particularly in nonpulmonary and non-Mycobacterium abscessus complex infections, researchers reported.
Rapidly growing mycobacteria (RGM) are associated with high rates of natural antibiotic resistance, limiting treatment options, the researchers wrote.
“RGM infections require prolonged courses of oral and intravenous broad-spectrum antibiotics with considerable associated toxicity,” Keith W. Hamilton, MD, director of antimicrobial stewardship, infectious diseases transition service and internal medicine clerkship and associate professor of clinical medicine at Penn Medicine, and colleagues wrote. “More effective and better-tolerated therapies are needed.”
According to Hamilton and colleagues, clofazimine (CFZ) is a riminophenazine antibiotic originally used to treat Mycobacterium leprae infections that has “promising in vitro activity in RGM, with minimum inhibitory concentrations of 1 mg/L or more for almost all isolates of [Mycobacterium fortuitum, Mycobacterium chelonae, and M. abscessus complex (MAbsC)]. However, clinical data regarding CFZ in RGM infection are limited.”
"The medication must be obtained through an Investigational New Drug approval so it is not available to hospitals or clinics without going through this pathway," Hamilton told Infectious Disease News. "Therefore, if this medication is considered for a patient, the patient should be referred to a clinician or treatment center that is familiar with obtaining this antibiotic."
The researchers conducted a retrospective cohort study in the University of Pennsylvania Health System that included all patients treated for RGM infection with a CFZ-containing regimen between Jan. 1, 2010, and Dec. 31, 2016. They defined clinical cure, the primary outcome, as “no evidence of clinical or microbiologic infection recurrence after 1 year following the completion of treatment.”
During the study period, 55 patients with RGM infection were treated with CFZ-containing regimens. CFZ was combined with a median of five other antibiotics during each treatment course.
The researchers reported that 43% of patients with a pulmonary infection and 71% of patients with a nonpulmonary infection achieved clinical cure with an initial treatment regimen. Premature discontinuation occurred in 20% of patients in the “context of discontinuing all antibiotic agents,” according to the study.
Hamilton and colleagues said CFZ was well tolerated and may be an effective treatment option for RGM infections.
“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,” they wrote. “While lower response rates for pulmonary disease and MAbsC infections demonstrate the need for better therapies, our findings provide an encouraging improvement over past experiences.” – by Marley Ghizzone
Disclosures: The authors report no relevant financial disclosures.
Perspective
Back to TopFelice C. Adler-Shohet, MD
Although CFZ has been used for decades, it has been used mainly to treat M. leprae infections. Only more recently have we seen reports of its repurposed use for multidrug-resistant tuberculosis and nontuberculous mycobacterial infections, both of which are increasing in incidence. RGM can cause serious lung infections in those with underlying pulmonary disorders and infections with these organisms, and M. abscessus in particular, can be extremely difficult to treat because of antimicrobial resistance and the morbidity of the regimen.
It is very encouraging that this study shows CFZ retains good activity against most RGM and can be a safe and well tolerated part of a multidrug regimen to treat RGM, including pulmonary infections. Clinical response to the CFZ-containing regimens described in this paper also seemed to be similarly or more effective than previously described regimens.
It is hoped that future studies will confirm these findings. There is also a need for additional studies describing the pharmacokinetics and pharmacodynamics of CFZ in patients with RGM infections, especially in children and those with cystic fibrosis because patients with cystic fibrosis seem to have some of the worst treatment outcomes.
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