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Antimicrobial Agents and Chemotherapy, February 2003, p. 524-528, Vol. 47, No. 2
0066-4804/03/$08.00+0 DOI: 10.1128/AAC.47.2.524-528.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Department of Pharmacology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma 74107-1898
Received 5 September 2002/ Returned for modification 11 October 2002/ Accepted 31 October 2002
Inhalation of fresh water containing the free-living ameba Naegleria fowleri may lead to a potentially fatal infection known as primary amebic meningoencephalitis. Amphotericin B is the only agent with established clinical efficacy in the treatment of primary amebic meningoencephalitis in humans, but therapy with this drug is often associated with adverse effects on the kidneys and other organs, and not all persons treated with amphotericin B have survived. We investigated the in vitro activity and in vivo efficacy of newer therapeutic agents in an attempt to identify other useful agents for treating primary amebic meningoencephalitis. Azithromycin has shown in vitro activity against Acanthamoeba spp. and in vivo activity against experimental toxoplasmosis. In our study, the MIC of azithromycin against N. fowleri was 13.4 µM (10 µg/ml), which was 123 times greater than the MIC of amphotericin B, which was 0.108 µM (0.1 µg/ml). Azithromycin protected 100% of mice infected with N. fowleri at a dose of 75 mg/kg/day for 5 days, whereas amphotericin B protected only 50% of mice at a dose of 7.5 mg/kg/day for 5 days, and all control mice died during the 28-day observation period. We conclude that azithromycin has both in vitro and in vivo activity versus N. fowleri and may be a useful addition to therapy for primary amebic meningoencephalitis.
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