Activities of Therapeutic Agents Against Naegleria Fowleri in Vitro and in a Mouse Model of Primary Amebic Meningoencephalitis

Abstract

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.

Therapeutic effect of rokitamycin in vitro and on experimental meningoencephalitis due to Naegleria fowleri

“…or Acanthamoeba spp. [7,9,26,27]. Although amphotericin B is the only agent used consistently as treatment for patients with PAME, amphotericin B is a very toxic antibiotic and may cause renal toxicity, electrolyte disturbances, haematopoietic effects and other organ damage, as well as chills, fever, nausea, vomiting and headache [11][12][13].…”

Human infections caused by free-living amoebae

“…All reported recoveries revealed that the patients were successfully cured by mixed treatment, but always with amphotericin B. Phenothiazine compounds (chlorpromazine and rifluoperazine), which can accumulate in the CNS, were tested in vitro and were found to have inhibitory effects on N. fowleri [20]. Azithromycin has been shown to be effective against Naegleria in a mouse model of disease both in vitro and in vivo [21]. Other macrolides are less effective.…”

Importance of Nonenteric Protozoan Infections in Immunocompromised People

“…However, amphotericin B is probably the drug of choice for the treatment of N. fowleri infection due to its successful use in a few cases of PAM (66,575). Amphotericin B has also demonstrated good anti-Naegleria activity in vitro (242,243,548,549). However, amphotericin B therapy is not always successful (503).…”