AI Article Synopsis
- - This study investigates the effects of Clofazimine (CFZ) on patients with Mycobacterium avium-intracellulare and Mycobacterium abscessus pulmonary diseases, focusing on identifying the optimal dosage by analyzing CFZ concentration in relation to safety and treatment outcomes.
- - Findings reveal that patients with moderate-to-severe pigmentation due to CFZ treatment had significantly higher drug concentrations, and a CFZ level of 1 mg/L was linked to a notable prolongation of the QTc interval.
- - The results indicate that while culture conversion occurred in a substantial number of patients, factors like previous surgery were more strongly associated with successful treatment outcomes than CFZ concentration alone.
Article Abstract
Background: Clofazimine (CFZ) has shown promising effects against Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) and Mycobacterium abscessus species pulmonary disease (MABS-PD). However, the optimal CFZ dose remains unknown. We aimed to explore the relationship between steady-state CFZ concentration and its safety and efficacy in MAC-PD and MABS-PD.
Methods: This prospective observational study focused on patients with MAC-PD and MABS-PD treated with CFZ (UMIN 000041053). To understand the safety and efficacy profile of CFZ and elucidate its optimal concentration, we analyzed CFZ-induced pigmentation grade, QTc interval, and culture conversion outcomes in relation to serum CFZ concentration using Student's t-test, a concentration-QTc model, and multivariable logistic regression analysis, respectively. In total, 64 patients (34 with MAC-PD; 30 with MABS-PD) were included.
Results: The steady-state concentration of CFZ was higher in the moderate-to-severe pigmentation group than in the none-to-light pigmentation group (P < 0.001). At a CFZ concentration of 1 mg/L, the QTc interval was prolonged by 17.3 ms (95 % confidence interval [CI], 3.9-25.4) from baseline. Culture conversion was achieved in 33 (51.6 %) patients. The only significant predictor of culture conversion was surgery (adjusted odds ratio, 5.4; 95 % CI, 1.3-38.0). CFZ concentration and MIC of CFZ less than 0.25 mg/L were not associated with culture conversion in this study.
Conclusion: CFZ-induced pigmentation and QT interval prolongation are associated with serum CFZ concentrations. CFZ dosage may be optimized by monitoring serum CFZ concentration.
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| http://dx.doi.org/10.1016/j.rmed.2024.107718 | DOI Listing |
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