title: Mefloquine, moxifloxacin, and ethambutol are a triple-drug alternative to macrolide-containing regimens for treatment of Mycobacterium avium disease.
abstract: 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 approximately 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.
authors.affiliation: Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco, California, USA. luizb@cooper.cpmc.org
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Bermudez
authors.forename: Peter
authors.initials: P
authors.lastname: Kolonoski
authors.forename: Mary
authors.initials: M
authors.lastname: Petrofsky
authors.forename: Martin
authors.initials: M
authors.lastname: Wu
authors.forename: Clark B
authors.initials: CB
authors.lastname: Inderlied
authors.forename: Lowell S
authors.initials: LS
authors.lastname: Young
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D001372:Aza Compounds; D017291:Clarithromycin / Q000494:pharmacology; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000494:pharmacology / Q000627:therapeutic use*; D024841:Fluoroquinolones; D015767:Mefloquine / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D000077266:Moxifloxacin; D015269:Mycobacterium avium Complex / Q000187:drug effects; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology; D011804:Quinolines
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000962:Antimalarials; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D004977:Ethambutol; D017291:Clarithromycin; D015767:Mefloquine; D000077266:Moxifloxacin