New drug swap cuts MAC infection burden by 40% in lab tests
Researchers found that replacing rifampicin with minocycline in combination therapy for Mycobacterium avium complex pulmonary disease reduced bacterial load significantly while potentially lowering drug toxicity and interactions. The finding could reshape treatment protocols for a chronic infection that currently achieves only 65% cure rates and burdens patients with substantial side effects.
Originaltitel: Replacing rifampicin with minocycline increases the activity of the treatment regimen for<em> Mycobacterium</em><em> avium</em> complex pulmonary disease in a dynamic hollow-fibre system
<p>Objective: Mycobacterium avium complex bacteria cause chronic pulmonary disease (MAC-PD) in susceptible patients. The recommended treatment regimen (rifampicin, ethambutol and azithromycin) achieves 65% cure rates but with considerable toxicity and drug-drug interactions [[2], [3]]. Minocycline proved active in monotherapy experiments using the hollow-fibre model [4]. We compared the efficacy of the recommended regimen with a minocycline, ethambutol and azithromycin regimen using this model.</p><p>Methods: Epithelial lining fluid pharmacokinetic (PK) profiles of the recommended regimen and minocycline, ethambutol, azithromycin regimen were simulated. THP-1 cells infected with M. avium ATCC 700898 were exposed to these regimens for 21 d. PK profiles were determined at d 0 and d 21. The pharmacodynamic effect was measured by determining bacterial densities at d 0, 3, 7, 14 and 21 for intra- and extracellular fractions. Emergence of macrolide-resistance was monitored by inoculating azithromycin-containing agar, MIC measurements and resistance mutation analysis.</p><p>Results: The minocycline-containing regimen exhibited a 1.5 log10 CFU/mL lower bacterial burden than the recommended regimen at d 7, though both regimens lost effectiveness over time. Treatment failure in both arms was not linked to the emergence macrolide-resistance. PK profiles simulated in the model matched those in MAC-PD patients. </p><p>Conclusions: Replacing rifampicin with minocycline increased the antimycobacterial activity of the MAC-PD treatment regimen in the hollow-fibre model, without jeopardizing the prevention of macrolide-resistance. This promising minocycline-containing regimen is a candidate for inclusion in clinical trials. (c) 2024 The Author(s).</p>