Activities of therapeutic agents against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis.
Inhalation of water contaminated with Naegleria fowleri may lead to a potentially fatal infection of the central nervous system known as primary amebic meningoencephalitis (PAM). Amphotericin B (AMB), an antifungal drug, is the only agent with established clinical efficacy in the treatment of PAM, though therapy with this drug is not always effective and has been associated with adverse effects on the kidneys and other organs. We investigated the activity of various therapeutic agents against N. fowleri in an attempt to identify other useful agents for treating PAM. Several of these agents exhibited in vitro activity against the Lee (M67) strain of N. fowleri. The minimum inhibitory concentrations of these agents were 0.1 microg/ml (ketoconazole), 1 microg/ml (liposomal AMB), and 10 microg/ml (minocycline, quinupristin-dalfopristin, and trifluoperazine). Other agents had a minimum inhibitory concentration > 10 microg/ml (linezolid) or > 100 microg/ml (rifampin). In a mouse model of PAM, none of the untreated control mice survived, whereas the survival of treated animals was 50% (quinupristin-dalfopristin), 30% (ketoconazole and liposomal AMB), 20% (trifluoperazine), and 10% (linezolid and minocycline). Further studies are needed to ascertain whether these agents have synergistic activity with AMB in vitro and in vivo.
Goswick
Shannon M
SM
Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma 74107-1898, USA.
Brenner
George M
GM
D000081:Acetamides / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000562:Amebiasis / Q000188:drug therapy* / Q000469:parasitology; D000563:Amebicides / Q000494:pharmacology* / Q000627:therapeutic use; D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D020808:Central Nervous System Protozoal Infections / Q000188:drug therapy* / Q000469:parasitology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology / Q000627:therapeutic use; D000069349:Linezolid; D008081:Liposomes; D008297:Male; D051379:Mice; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use; D016848:Naegleria fowleri / Q000187:drug effects*; D023303:Oxazolidinones / Q000494:pharmacology / Q000627:therapeutic use; D014268:Trifluoperazine / Q000494:pharmacology / Q000627:therapeutic use; D014769:Virginiamycin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000081:Acetamides; D000563:Amebicides; D008081:Liposomes; D023303:Oxazolidinones; D014769:Virginiamycin; D014268:Trifluoperazine; C113825:quinupristin; D000666:Amphotericin B; D008911:Minocycline; D000069349:Linezolid; D007654:Ketoconazole; C113826:dalfopristin