Primary Amoebic Meningoencephalitis in Britain

In vitro effects of the polvene antibiotic amphotericin B (AmB) on growth, viability, and ultrastructure of amoeboflagellates of the genus Naegleria were examined. The strains studied were the nonpathogenic Naegleria gruberi EGB and the Carter and TY strains of the pathogenic Naegleria fowleri. AmB was amoebicidal at all concentrations used (0.25, 0.50, and 1.0 ,ug/ml) when the drug was added to cultures in lag phase, as determined by viability testing, but was mainly inhibitory when added to log-phase cultures. The drug produced ultrastructural modifications at all concentrations (0.05 to 1.0 gg/ml). These changes included distortion of nuclear shape, increase in cytoplasmic membranes (both rough and smooth endoplasmic reticulum), decrease in number of food vacuoles, absence of pseudopod formation, mitochondrial abnormalities, increase in autophagic vacuoles, and blebbing of the plasma membrane. These alterations of amoebic ultrastructure became more pronounced with increased time in AmB and with increase in AmB concentration in the growth medium.

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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In Vitro Effects of Amphotericin B on Growth and Ultrastructure of the Amoeboflagellates Naegleria gruberi and Naegleria fowleri

Schuster

Rechthand

1975

“…Studies have demonstrated the in vitro and in vivo activity of amphotericin B against various strains of N. fowleri (5-8, 13, 17, 19, 20, 21), and at least seven patients with primary amebic meningoencephalitis have been successfully treated with amphotericin B alone or in combination with other drugs (1,2,14,16,19,25).…”

mentioning

confidence: 99%

Activities of Azithromycin and Amphotericin B against Naegleria fowleri In Vitro and in a Mouse Model of Primary Amebic Meningoencephalitis

Goswick

Brenner

2003

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 M (10 g/ml), which was 123 times greater than the MIC of amphotericin B, which was 0.108 M (0.1 g/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.Primary amebic meningoencephalitis is a rapidly fatal infection caused by the free-living ameba Naegleria fowleri. Victims are usually healthy, young individuals with a recent history of swimming or other water-related activities. N. fowleri gains entry to the nasal cavity during inhalation or aspiration of contaminated water. The ameba then migrates along the olfactory nerves, crosses the cribriform plate, and gains access to the central nervous system. Within the brain, N. fowleri causes extensive inflammation, hemorrhage, and necrosis, leading to death in 3 to 7 days (12).Mortality among patients with primary amebic meningoencephalitis is greater than 95% (4). This grave prognosis is due to the rapid progression of the disease, the often delayed diagnosis, and the lack of effective therapeutic agents. Since primary amebic meningoencephalitis was identified, a wide range of therapeutic agents against N. fowleri have been evaluated, including many antifungal, antiprotozoal, antibacterial, and antipsychotic agents. Most of these drugs were determined to have little or no efficacy against N. fowleri, either in vitro or in vivo (5)(6)(7)(8)22).Of the drugs that have been evaluated against N. fowleri, amphotericin B, an antifungal drug, is the only agent with established clinical efficacy. Studies have demonstrated the in vitro and in vivo activity of amphotericin B against various strains of N. fowleri (5-8, 13, 17, 19, 20, 21), and at least seven patients with primary amebic meningoencephalitis have been successfully treated with amphotericin B alone or in combination with other drugs (1,2,14,16,19,25).Although amphotericin B remains the first choice for treatment of primary amebic me...

“…PAM, caused by free-living amoebae of the genus Naegleria, usually results in death; of the approximately 80 documented cases, there have been only three survivors (1,2,6). Many different antimicrobial agents (and treatment regimens) have been used to treat PAM, but the most promising appears to be the antifungal polyene, AMB.…”

mentioning

confidence: 99%

In Vitro Susceptibilities of Naegleria fowleri Strain HB-1 to Selected Antimicrobial Agents, Singly and in Combination

Lee

Karr

Wong

et al. 1979

The overall prognosis of primary amoebic meningoencephalitis remains poor. The results of this study support previous finding that amphotericin B is the most efficacious drug against the Naegleria species in in vitro testing. In additon, the methyl ester of amphotericin B, a new derivative, also appears to be an effective agent. Of the drug combinations studied, amphotericin B plus minocycline and amphotericin B plus tetracycline showed synergy. The clinical significance of these findings remains to be determined.A strain of Naegleria fowleri (HB-1) was tested in vitro for susceptibility to amphotericin B (AMB), the methyl ester of AMB, miconazole, minocycline, and tetracycline, both singly and in combination with one another. The mean minimal inhibitory concentrations (MICs), defined as an absence of cytopathic effect by amoebae on monkey kidney cell (MKC) monolayers, were, respectively: AMB, 0.024 ug/ml; methyl ester of AMB, 0.103 ug/ml; minocycline, 2.8 ,ug/ ml; miconazole, 6.25 lAg/ml; and tetracycline, 10.0 ,ug/ml. Synergism