Drug combinations including clofazimine were effective in treating 54% of patients with rapidly growing mycobacterial infections, including 71% whose infections were non-pulmonary, new research found.
Clofazimine used in combination with other drugs, may be an option to treat some people with rapidly growing mycobacterial infections, new research has found.
The retrospective cohort study, published in Open Forum Infectious Diseases, included 55 patients treated with clofazimine, which is a riminophenazine antibiotic originally used for Mycobacterium leprae infections, in combination with other antibiotics in the University of Pennsylvania Health System from 2010 to 2016.
“Rapidly growing mycobacterial (RGM) infections are becoming more common,” corresponding author Keith Hamilton, MD, associate professor of clinical medicine and attending physician at the Hospital of the University of Pennsylvania, told Contagion®. “Treatment for these challenging infections often requires regimens that include several antibiotics, but treatment options are limited, contributing to historically poor cure rates. Because many antibiotic regimens must include intravenous antibiotics, adverse drug events and toxicity are common. Clofazimine may offer a safe and effective oral treatment option as a part of a multidrug antibiotic regimen.”
A daily dose of 100 mg of clofazimine was used. The investigators found that 71% of patients with non-pulmonary infection and 43% of those with pulmonary infection were cured, with no recurrence 1 year after treatment. The cure rate for all patients was 54% overall.
Among 22 patients with pulmonary disease, all had the species M abscessus complex (MAbsC). Among those without pulmonary disease, had 9 (39%) had M abscessus/bolletii, 2 (9%) had M massiliense, 9 (39%) had M chelonae, and 3 (13%) had M fortuitum.
“Even using multiple antibiotics that have in vitro susceptibility against RGM result in suboptimal cure rates, especially in pulmonary infections, Mycobacterium abscessus subspecies abscessus infections, and macrolide-resistant infections. Only 54% of all patients achieved clinical cure, but this cure rate is higher than that reported in some prior studies,” Hamilton told Contagion®.
RGM infections have proven difficult to cure, complicated by underlying pulmonary diseases or immunosuppression in many patients. RGM infections are increasing in the United States, making the disease an emerging health concern, the study noted.
“For the first time, we demonstrate that multidrug antibiotic regimens containing clofazimine can result in durable clinical cure for RGM after 12 months of follow up,” Hamilton told Contagion®. “Higher cure rates appear to be associated with non-pulmonary infections and infections caused by RGM other than Mycobacterium abscessus subspecies abscessus and by RGM that are macrolide-susceptible. However, the use of these multidrug regimens still requires close monitoring and use of medications that may be challenging to access due to restrictions, route of administration, or insurance coverage. Therefore, referral to providers with experience in treating RGM infections may facilitate more efficient treatment.”
Clofazimine was found to be well-tolerated, with only 20% of patients experiencing adverse effects significant enough to require discontinuation of all drugs in the treatment, the study said, noting that it was difficult to determine whether the effects were due to clofazimine or other antibiotics in the treatment. Those side effects included fatigue/malaise, nausea/vomiting/diarrhea, QTc prolongation, and drug-induced hepatitis. The most commonly reported adverse drug response was skin pigmentation, which was reported in 84% of patients.
“Study of clofazimine in larger patient cohorts and in combination with newer antibiotics that may have activity against RGM is warranted,” Hamilton told Contagion®. “New and more effective treatment options are still needed to treat these challenging infections.”
Clofazimine is among a range of emerging therapies being explored to treat non-tuberculosis mycobacteria. New drugs in the pipeline include bedquiline, delamanid, cyclines and SPR719. Others being repurposed include an inhaled preparation of amikacin enclosed in liposomes, linezolid/tedizolid, beta-lactams, and rifamycin.