Survival of Naegleria fowleri primary amebic meningocephalitis (PAM) could be improved with an intensive multi-route chemo- and biotherapeutic regimen.

BACKGROUND Naegleria fowleri primary amebic meningoencephalitis (PAM) has a very high mortality rate, probably exceeding 95%. A few people have survived after getting intravenous and intrathecal amphotericin, variably coupled with other agents that include dexamethasone, diflucan, chloramphenicol and rifampin, but even with prompt initiation of therapy, it is still a very uphill battle. PRESENTATION OF THE HYPOTHESIS Survival could be improved by combined intrathecal, intranasal and intravenous amphotericin, diflucan and rifampin, with aduvant intravenous chloramphenicol, muramyl dipeptide, azithromycin, minocycline and linezolid, intramuscular trifluoperazine, intranasal Cry1C protoxin and intrathecal anti-Naegleria immune globulin and dexamethasone. HYPOTHESIS RATIONALE: Instilling medications intranasally, intravenously and intrathecally would target the primary reservoir of infection and its common sites of spread. Intrathecal dexamethasone should attenuate cerebral edema, a primary cause of death in PAM. Azithromycin and minocycline appear to have synergy with amphotericin in killing N. fowleri in animal models, and the other agents, which also showed efficacy in animal models, should also be additive or synergistic as well. In essence one would approach PAM in the manner of chemotherapy for tuberculosis and cancer, with multidrug therapy to assure complete eradication. TESTING THE HYPOTHESIS The hypothesis could be validated using murine and bovine models of N. fowleri PAM. IMPLICATIONS OF THE HYPOTHESIS PAM may be emerging as a significant public health threat, underscoring the need for effective therapeutic regimens.