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Identification of (+)-Erythro-Mefloquine as an Active Enantiomer with Greater Efficacy than Mefloquine against Mycobacterium avium Infection in Mice

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dc.creator Bermudez, Luiz E.
dc.creator Inderlied, Clark B.
dc.creator Kolonoski, Peter
dc.creator Chee, Christopher B.
dc.creator Aralar, Priscilla
dc.creator Petrofsky, Mary
dc.creator Parman, Toufan
dc.creator Green, Carol E.
dc.creator Lewin, Anita H.
dc.creator Ellis, William Y.
dc.creator Young, Lowell S.
dc.date.accessioned 2012-11-14T01:12:10Z
dc.date.available 2012-11-14T01:12:10Z
dc.date.issued 2012-08
dc.identifier.citation Bermudez, L. E., Inderlied, C. B., Kolonoski, P., Chee, C. B., Aralar, P., Petrofsky, M., ... Young, L. S. (2012, August). Identification of (+)-Erythro-Mefloquine as an Active Enantiomer with Greater Efficacy than Mefloquine against Mycobacterium avium Infection in Mice. Antimicrobial Agents and Chemotherapy, 56(8), 4202-4206. doi:10.1128/AAC.00320-12 en_US
dc.identifier.uri http://hdl.handle.net/1957/35064
dc.description This is the publisher’s final pdf. The published article is copyrighted by the American Society for Microbiology and can be found at: http://aac.asm.org/. To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work. en_US
dc.description.abstract Infection caused by Mycobacterium avium is common in AIDS patients who do not receive treatment with highly active antiretroviral therapy (HAART) or who develop resistance to anti-HIV therapy. Mefloquine, a racemic mixture used for malaria prophylaxis and treatment, is bactericidal against M. avium in mice. MICs of (+)-erythro-, (−)-erythro-, (+)-threo-, and (−)-threo-mefloquine were 32 μg/ml, 32 μg/ml, 64 μg/ml, and 64 μg/ml, respectively. The postantibiotic effect for (+)-erythro-mefloquine was 36 h (MIC) and 41 h for a concentration of 4× MIC. The mefloquine postantibiotic effect was 25 h (MIC and 4× MIC). After baseline infection was established (7 days), the (+)- and (−)-isomers of the diastereomeric threo- and erythro-α-(2-piperidyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol were individually used to orally treat C57BL/6 bg+/bg+ beige mice that were infected intravenously with M. avium. Mice were also treated with commercial mefloquine and diluent as controls. After 4 weeks of treatment, the mice were harvested, and the number of bacteria in spleen and liver was determined. Mice receiving (+)- or (−)-threo-mefloquine or (−)-erythro-mefloquine had numbers of bacterial load in tissues similar to those of untreated control mice at 4 weeks. Commercial mefloquine had a bactericidal effect. However, mice given the (+)-erythro-enantiomer for 4 weeks had a significantly greater reduction of bacterial load than those given mefloquine. Thus, (+)-erythro-mefloquine is the active enantiomer of mefloquine against M. avium and perhaps other mycobacteria. en_US
dc.description.sponsorship This work was supported by contract numbers N02-AI-75322 and NO1-AI-05417 of the National Institute of Allergy and Infectious Diseases. en_US
dc.language.iso en_US en_US
dc.publisher American Society for Microbiology en_US
dc.relation.ispartofseries Antimicrobial Agents and Chemotherapy en_US
dc.relation.ispartofseries Vol. 56 no. 8 en_US
dc.title Identification of (+)-Erythro-Mefloquine as an Active Enantiomer with Greater Efficacy than Mefloquine against Mycobacterium avium Infection in Mice en_US
dc.type Article en_US
dc.description.peerreview yes en_US
dc.identifier.doi 10.1128/AAC.00320-12


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