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Mycobacterium avium complex bacteria cause severe and difficult to treat opportunistic pulmonary infections. Current treatment regimens of rifampicin, ethambutol and azithromycin have cure rates as low as 50%. These low cure rates despite aggressive and highly toxic regimens are unacceptable and new regimens are urgently needed.
Drug repurposing is an attractive way to build new regimens fast. Using the animal-free hollow fiber model, Sandra Salillas Berges and Jelmer Raaijmakers from the Department of Medical Microbiology (PI: Jakko van Ingen) demonstrated that treatment regimens become much more effective if rifampicin is replaced by clofazimine. Clofazimine is an old anti-leprosy drug. The high efficacy was seen for a 200mg once daily dose, which is higher than current doses in leprosy and tuberculosis treatment. Yet, this dose has been widely and safely applied in leprosy treatment in the past. The results are published in the Antimicrobial Agents and Chemotherapy journal, on 6 March.
The logical next step is a series of clinical studies on the safety and pharmacokinetics of these higher doses in actual patients. Radboudumc is the national reference center for treatment of these complex infection and has experience doing clinical trials for these infections. The first trial investigating the safety of higher loading doses has recently been completed. The potential of administering higher doses via inhalation will be studied next, both in the hollow fiber model and in a clinical trial.
Read the study here:
Salillas S, Raaijmakers J, Aarnoutse RE, Svensson EM, Asouit K, van den Hombergh E, Te Brake L, Stemkens R, Wertheim HFL, Hoefsloot W, van Ingen J. Clofazimine as a substitute for rifampicin improves efficacy of Mycobacterium avium pulmonary disease treatment in the hollow-fiber model. Antimicrob Agents Chemother. 2024 Mar 6;68(3):e0115723. doi: 10.1128/aac.01157-23.
