Mefloquine, Moxifloxacin, and Ethambutol Are a Triple-Drug Alternative to Macrolide-Containing Regimens for Treatment of Mycobacterium avium Disease

• Published in: The Journal of infectious diseases Vol. 187; no. 12; pp. 1977 - 1980
• Main Authors: Bermudez, Luiz E, Kolonoski, Peter, Petrofsky, Mary, Wu, Martin, Inderlied, Clark B, Young, Lowell S
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.06.2003; University of Chicago Press; Oxford University Press
• Subjects: AIDS; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Anti-Infective Agents - pharmacology; Anti-Infective Agents - therapeutic use; Antibacterial agents; Antibacterials; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - pharmacology; Antimalarials - therapeutic use; Aza Compounds; Bacteria; Biological and medical sciences; Clarithromycin - pharmacology; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Ethambutol - pharmacology; Ethambutol - therapeutic use; Fluoroquinolones; Fungal infections; Infections; Liver; Lung diseases; Macrolides; Medical sciences; Mefloquine - pharmacology; Mefloquine - therapeutic use; Mice; Mycobacterium avium; Mycobacterium avium complex; Mycobacterium avium Complex - drug effects; Mycobacterium avium-intracellulare Infection - drug therapy; Mycobacterium avium-intracellulare Infection - microbiology; Pharmacology. Drug treatments; Quinolines; Spleen; Antimalarial; Mefloquine; Mycobacterium avium; Moxifloxacin; Macrolide; Chemotherapy; Fluoroquinolone derivatives; Treatment; Mycobacteriales; Parasiticid; Mycobacteriaceae; Bacteria; Ethambutol; Actinomycetes; Antituberculous agent; Antibacterial agent; Quinolone derivatives
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/375352

Macrolides are the core of effective drug regimens for the treatment of Mycobacterium avium complex (MAC) disease. Mefloquine (MFQ), moxifloxacin (MXF), and ethambutol (EMB), in combination, were evaluated against both clarithromycin-resistant (CLR-R) and CLR-susceptible (CLR-S) MAC; MFQ (40 mg/kg), MXF (100 mg/kg), or EMB (100 mg/kg/day) was given to mice for 4 weeks. MFQ was bactericidal, whereas MXF and EMB were bacteriostatic against both MAC 101 CLR-S and CLR-R. The combination of MFQ and EMB reduced (P<.05, for comparison with controls), and the combination of MFQ and MXF significantly reduced, the load of CLR-R in both the liver and the spleen. Treatment with all 3 drugs was associated with ∼1-log reduction of CLR-R after 1 week, 2.1-log reduction of CLR-R after 4 weeks, and 2.17-log reduction in MAC/mL blood. Treatment of MAC 101 CLR-S strain had comparable results