Treatment

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Clinicians: For 24/7 diagnostic assistance, specimen collection guidance, shipping instructions, and treatment recommendations, please contact the CDC Emergency Operations Center at 770-488-7100. More detailed guidance is under Information for Public Health & Medical Professionals.

CDC no longer provides miltefosine for treatment of free-living ameba infections. Miltefosine is now commercially available. Please visit impavido.com for more information on obtaining miltefosine in the United States. If you have a patient with suspected free-living ameba infection, please contact the CDC Emergency Operations Center at 770-488-7100 to consult with a CDC expert.

Survivor Medications

Although most cases of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri infection have been fatal,1 there have been five documented survivors (one from the United States in 1978,2,3 one from Mexico in 2003,4 two from the United States in 2013,5,6 and one from the United States in 2016) who received the following treatment:

Survivor Medications
U.S. Survivor2,3 (1978) Mexico Survivor4 (2003) U.S. Female Survivor5 (2013) U.S. Male Survivor6 (2013
Amphotericin B (IV and intrathecal) Amphotericin B (IV) Amphotericin B (IV and intrathecal) Amphotericin B (IV and intrathecal)
Rifampin (oral) Rifampin (oral) Rifampin (IV/oral) Rifampin (oral)
Miconazole (IV and intrathecal) – no longer available in US Fluconazole (IV and oral) Fluconazole (IV/oral) Fluconazole (IV)
Dexamethasone Dexamethasone (IV) Dexamethasone (IV) Dexamethasone (IV)
Sulfisoxazole (IV) – discontinued after Naegleria diagnosed Ceftriaxone (IV) Azithromycin (IV/oral) Azithromycin (IV/oral)
Phenytoin Miltefosine (oral) Miltefosine (oral)

*The 2016 U.S. survivor received the same treatment protocol as the 2013 U.S. female survivor.

Recommended Treatment for Primary Amebic Meningoencephalitis Caused by Naegleria fowleri

Recommended Treatment for Primary Amebic Meningoencephalitis Caused by Naegleria fowleri
Drug Dose Route Maximum Dose Duration Comments
Amphotericin B *2 1.5 mg/kg/day in 2 divided doses IV 1.5 mg/kg/day 3 days

then

 1 mg/kg/day once daily IV 11 days 14-day course
Amphotericin B *2 1.5 mg once daily Intrathecal 1.5 mg/day 2 days

then

 1 mg/day every other day Intrathecal 8 days 10-day course
Azithromycin 8,11 10 mg/kg/day once daily IV/PO 500 mg/day 28 days
Fluconazole 4 10 mg/kg/day once daily IV/PO 600 mg/day 28 days
Rifampin 2 10 mg/kg/day once daily IV/PO 600 mg/day 28 days
Miltefosine ** Weight<45 kg 50 mg BID
Weight>45kg 50 mg TID		 PO 2.5 mg/kg/day 28 days 50 mg tablets
Dexamethasone 4,18 0.6 mg/kg/day in 4 divided doses IV 0.6 mg/kg/day 4 days

* Conventional amphotericin (AMB) is preferred. When AMB was compared with liposomal AMB against Naegleria fowleri, the minimum inhibitory concentration (MIC) for AMB was 0.1 µg/mL, while that of liposomal AMB was 10x higher at 1 µg/ml. Liposomal AMB was found to be less effective in the mouse model and in in vitro testing than the more toxic form of AMB 7,8. AMB methyl ester was also found to be less effective in the mouse model 9,10. Because of the extremely poor prognosis of Naegleria fowleri infection, it’s worth considering aggressive treatment.

** Miltefosine 12, a breast cancer and anti-leishmania drug, has shown some promise against the free-living amebae in combination with some of these other drugs. Miltefosine has shown in vitro and mouse model amebicidal activity against Balamuthia, Naegleria fowleri, and Acanthamoeba 13-15 and has been used to successfully treat patients with Balamuthia infection 16 and disseminated Acanthamoeba infection 17. The standard miltefosine dosing in adults is as follows:

Miltefosine (oral)

  • Up to 45 kg body weight: 100 mg daily (i.e., one 50 mg cap po BID, given with food if possible to reduce gastrointestinal side effects)
  • 45 kg body weight and higher: 150 mg daily (i.e., one 50 mg cap po TID, given with food if possible to reduce gastrointestinal side effects)

These standard doses are the maximal tolerated with respect to gastrointestinal symptoms. A higher dose would lead to increased nausea, vomiting, or diarrhea. Miltefosine is mildly nephrotoxic and the dosing might need to be adjusted for patients with impaired kidney function. However, because few data are available about the effective dose for amebic infection, the risk for nephrotoxicity should be balanced with the risk for mortality from PAM. If you have a patient with suspected Naegleria or other free-living ameba infection, please contact the CDC Emergency Operations Center at 770-488-7100 to consult with a CDC expert.

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  2. Seidel J, Harmatz P, Visvesvara GS, Cohen A, Edwards J, Turner J. Successful treatment of primary amebic meningoencephalitis. New Engl J Med 1982;306:346-8.
  3. Visvesvara GS, Moura H, Schuster FL. Pathogenic and opportunistic free-living amoebae: Acanthamoeba, Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol Med Microbiol. 2007;50:1-26.
  4. Vargas-Zepeda J, Gomez-Alcala AV, Vasquez-Morales JA, Licea-Amaya L, De Jonckheere JF, Lores-Villa F. Successful treatment of Naegleria PAM using IV amphotericin B, fluconazole, and rifampin. Arch Med Res. 2005;36:83-6.
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