Amebic Meningoencephalitis Treatment & Management

Updated: Oct 12, 2021
  • Author: Linda Nguyen, MD; Chief Editor: Russell W Steele, MD  more...
  • Print

Approach Considerations

Admit patients with amebic meningoencephalitis to the intensive care unit (ICU) for intensive monitoring and therapy. Arrange transfer if appropriate specialists and resources are otherwise unavailable.

Typically, PAM rapidly progresses, appearing like an overwhelming acute bacterial meningitis unresponsive to routine antibacterial agents.



Measures to prevent PAM and GAE include the following:

  • The clinician should routinely discuss with individuals the risks of exposure to free-living amoebae in warm, typically stagnant, freshwater

  • Some have advocated the avoidance of diving and jumping into these waters

  • Advise individuals to consider the use of nose plugs for unavoidable exposures

  • Advise individuals to verify adequate chlorination of swimming pools

  • Since Acanthamoeba can cause keratitis, contact lens wearers should be advised to visit their provider for regular eye exams, replace contacts as prescribed, remove lenses before activity involving contact with water, wash hands with soap before handling contact lenses, and clean lenses as instructed by manufacturer

  • Immunocompromised patients are more susceptible to developing these infections, however, there are no additional preventive measures for this population



Emergent consultations with infectious disease specialists, neurologists, and neurosurgeons are recommended if PAM or GAE is suspected. There is 24/7 diagnostic assistance, specimen collection guidance with shipping instructions, and treatment recommendations offered by the CDC Emergency Operations Center at 770-488-7100. The CDC also offers an investigational drug called Miltefosine for free-living ameba infections caused by N. fowleri, B. mandrillaris, and Acanthamoeba species.


Medical Care

In both PAM and GAE, the mortality rate is approximated at 95%, and all survivors have received combination amoebicidal therapy.  Because of the low incidence of these infections and the high mortality rate, there have been no clinical trials to date defining optimal therapy. CDC recommendations are based on data accumulated from published case reports and in vitro data.

Primary amebic meningoencephalitis

The cornerstone of PAM treatment is amphotericin B deoxycholate (AMB), at maximally tolerated doses, plus miltefosine with adjunctive therapy. The CDC currently recommends the following multidrug regimen:

  • Amphotericin B 1.5 mg/kg/day intravenous (IV) in 2 divided doses for 3 days, then 1 mg/kg/day for 11 days

  • Amphotericin B 1.5 mg intrathecal daily for 2 days, then 1 mg/day every 48 hours for the next 8 days

  • Azithromycin 10 mg/kg/day IV/oral (PO) for 28 days

  • Fluconazole 10mg/kg/day IV/PO for 28 days

  • Rifampin 10 mg/kg/day IV/PO for 28 days

  • Miltefosine 50 mg bid (if weight is less than 45 kg) and 50mg tid (if weight is more than 45 kg) PO for 28 days

  • Dexamethasone 0.6 mg/kg/day IV in 4 divided doses for 4 days

In vitro studies and mouse models have indicated that miltefosine, chlorpromazine, and rokitamycin may have activity against PAM. Miltefosine in particular has been used in 2 of the 5 known cases to have survived.  In the first, the treatment regimen, which included miltefosine as well as induced hypothermia, there was complete neurologic recovery (32-34C). [21] The second patient, also treated with miltefosine but without induced hypothermia, survived with permanent brain damage. [34] Thus, the CDC recommends miltefosine as well as amphotericin B deoxycholate as the backbone of any treatment regimen.

Of note, although liposomal formulations of AMB tend to be preferred for other types of CNS infections, the conventional formulation, amphotericin B deoxycholate, is the preferred formulation for PAM and GAE. In vitro data indicates that for N. fowleri, the minimum inhibitory concentration (MIC) for conventional AMB was 0.1 ug/mL compared to an MIC of 1 ug/mL for liposomal AMB.

Steroids, which have a protective role against short-term neurologic sequelae, mortality, and severe hearing loss in patients with bacterial meningitis, are recommended for PAM for the same theoretical benefits.

Granulomatous amebic encephalitis

There has been success with several combination treatment regimens:


  • Several cases: Pentamidine +Sulfadiazine + Flucytosine + Fluconazole or Itraconazole

  • AIDS: Sulfadiazine + Pyrimethamine + Fluconazole + surgical resection of CNS lesion

  • Chronic Acanthamoeba meningitis: Trimethoprim/Sulfamethoxazole + Rifampin + Ketoconazole

  • Disseminated cutaneous infection: IV Pentamidine + topical Chlorhexidine + 2% Ketoconazole cream, followed by PO Itraconazole + Voriconazole + Amphotericin B lipid complex

Balamuthia mandrillaris

  • Two cases: Flucytosine + Pentamidine + Fluconazole + Sulfadiazine + Azithromycin or Clarithromycin + surgical resection of CNS lesion

  • One case: Pentamidine + Fluconazole + Sulfadiazine + Clarithromycin

Sappinia diploidea (1 case)

  • Azithromycin + Pentamidine + Itraconazole + flucytosine + surgical resection of CNS lesion

In conjunction with the FDA, the CDC has an expanded access investigational new drug (IND) protocol in effect to make miltefosine, an amebicidal agent, available directly from the CDC for treatment of free-living amebae (FLA) in the United States. These infections include primary amebic meningoencephalitis (PAM) caused by N. fowleri and granulomatous amebic encephalitis caused by B. mandrillaris and Acanthamoeba species. [35]


Surgical Care

Primary amebic meningoencephalitis

PAM may require the placement of a reservoir for intrathecal amphotericin B or miconazole. Hydrocephalus may necessitate shunting.

Granulomatous amebic encephalitis

Brain biopsy is essential for diagnosis. Excision of solitary or isolated lesions may be of clinical benefit. Retrospective analysis of survival cases show a combination of surgical management and antibiotic therapy. [36] Hydrocephalus may necessitate shunting.