Key points
- Primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri is treated with a combination of medications.
- There have been five well-documented survivors of PAM in North America.
Medication options
Recommended treatment for PAM caused by Naegleria fowleri infection
A combination of medications is recommended for treatment of Naegleria fowleri infections. These drugs have been used in PAM survivors. Many have been found to have antiamebic activity against Naegleria fowleri in the laboratory.
| Drug | Dose | Route | Maximum Dose | Duration | Comments |
|---|---|---|---|---|---|
| Amphotericin B1 | 1.5 mg/kg/day in 2 divided doses, THEN | IV | 1.5 mg/kg/day | 3 days | |
| 1 mg/kg/day once daily | IV | 11 days | 14-day course | ||
| Amphotericin B | 1.5 mg once daily, THEN | Intrathecal | 1.5 mg/day | 2 days | |
| 1 mg/day every other day | Intrathecal | 8 days | 10-day course | ||
| Azithromycin | 10 mg/kg/day once daily | IV/PO | 500 mg/day | 28 days | |
| Posaconazole2,3 |
Note to providers: Posaconazole dosing must be monitored and adjusted according to your institution’s therapeutic drug monitoring protocols. Optimal dosing for Naegleria fowleri infections is unknown. Below is a suggested initial regimen. Consult infectious disease specialists or clinical pharmacists for guidance. Adults (IV or DRT):
Children (IV or DRT):
|
IV/PO | 300 mg/day | 28 days | Review footnote below for important considerations |
| Rifampin | 10 mg/kg/day once daily | IV/PO | 600 mg/day | 28 days | |
| Miltefosine4 | Weight<45 kg 50 mg BID Weight>45kg 50 mg TID |
PO | 2.5 mg/kg/day | 28 days | 50 mg tablets |
| Dexamethasone | 0.6 mg/kg/day in 4 divided doses | IV | 0.6 mg/kg/day | 4 days | |
| Nitroxoline5 | Contact ÐÇ¿ÕÓéÀÖ¹ÙÍø for dosing |
1Conventional 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. AMB methyl ester was also found to be less effective in the mouse model. Because the prognosis of Naegleria fowleri infection is extremely poor, consider aggressive treatment.
2Posaconazole has been found to have superior in vitro activity and may be more effective than fluconazole, which has been historically recommended and used in the treatment regimen for 3 of 4 U.S. survivors. Isavuconazole has also shown in vitro activity, though studies are limited. Azole selection should be considered on an individual basis.
3 Due to limited availability, limited data, and variable absorption for some posaconazole formulations, intravenous (IV) and delayed release tablet (DRT) enteral formulations are preferred. Some clinicians have Immediate release suspension is not recommended.
4The table lists the standard miltefosine dose in adults. A higher dose leads to increased nausea, vomiting, or diarrhea. Miltefosine is mildly nephrotoxic and the dosing may need to be adjusted for patients with impaired kidney function. However, few data are available about the effective dose for amebic infection. The risk of nephrotoxicity should be balanced with the risk for death from PAM. Miltefosine is now commercially available. Please visit for more information.
5Nitroxoline is an investigational drug that may be effective for Naegleria fowleri infections. It is not FDA-approved in the United States, but available for treatment of free-living ameba infections through ÐÇ¿ÕÓéÀÖ¹ÙÍø's expanded access Investigational New Drug program. Contact the ÐÇ¿ÕÓéÀÖ¹ÙÍø Emergency Operations Center at 770-488-7100 for more information.
Survivor medications
Medications given to people who survived PAM
Although most people who get PAM caused by a Naegleria fowleri infection don't survive, there have been five documented cases of survivors in North America.
| U.S. Survivor (1978) |
Mexico Survivor (2003) |
U.S. Female Survivor (2013) |
U.S. Male Survivor (2013) |
U.S. Survivor (2016) |
|---|---|---|---|---|
| Amphotericin B (IV and intrathecal) |
Amphotericin B (IV) |
Amphotericin B (IV and intrathecal) |
Amphotericin B (IV and intrathecal) |
Amphotericin B (IV and intrathecal) |
| Rifampin (oral) |
Rifampin (oral) |
Rifampin (IV/oral) |
Rifampin (oral) |
Rifampin (IV/oral) |
| Miconazole (IV and intrathecal) No longer available in the U.S. |
Fluconazole (IV and oral) |
Fluconazole (IV/oral) |
Fluconazole (IV) |
Fluconazole (IV/oral) |
| Sulfisoxazole (IV) Discontinued after Naegleria fowleri infection diagnosed |
Ceftriaxone (IV) |
Azithromycin (IV/oral) | Azithromycin (IV/oral) |
Azithromycin (IV/oral) |
| Phenytoin | Miltefosine (oral) |
Miltefosine (oral) |
Miltefosine (oral) |
|
| Dexamethasone | Dexamethasone (IV) | Dexamethasone (IV) | Dexamethasone (IV) | Dexamethasone (IV) |