Treatment

Effective treatment for infections caused by Balamuthia mandrillaris has not been established. The following recommendations are based on the small number of Balamuthia survivor case reports in the literature.

The following combination of five drugs has been successfully given to the few survivors of Balamuthia GAE and should be given in combination to a patient with suspected or confirmed Balamuthia GAE:

Recommended Treatment for Granulomatous Amebic Encephalitis Caused by Balamuthia mandrillaris ^†

^† Duration of treatment has not been established. In case reports of survivors, duration of treatment has ranged from several weeks to several months or even years. The decision to stop treatment should be made on a case-by-case basis and include consideration of the patient’s clinical status and review of laboratory and radiographic findings. Empiric trials of amphotericin B have not been successful.

^a Azithromycin has been used successfully in combination therapy to treat Balamuthia infection, but was changed in some cases to clarithromycin because of persistent elevation of creatinine levels (concern about interstitial nephritis with azithromycin), and potentially better penetration of clarithromycin into the cerebrospinal fluid; however, in vitro studies indicate that azithromycin is more active than clarithromycin against other free-living amebae (Naegleria).

^b Recently, miltefosine, an anti-leishmania drug, has shown some promise in combination with some of these other drugs. Miltefosine has shown good in vitro amebicidal activity against Balamuthia and has been used to successfully treat a few patients with Balamuthia GAE and disseminated Acanthamoeba (another free-living ameba) in combination with some of the drugs listed above. The standard miltefosine dosing recommended for the treatment of leishmaniasis is presented in the table. Unfortunately, the oral preparation is the only formulation available.

^c The standard doses of miltefosine listed above are the maximal tolerated with respect to gastrointestinal symptoms. A higher dose would lead to increased nausea, vomiting, or diarrhea. Miltefosine is mildly nephrotoxic but is not cleared by the kidneys; therefore, dosing does not need to be adjusted for patients with impaired renal function. Because little data are available about the effective dose for amebic infection, the risk for nephrotoxicity should be balanced with the risk for mortality from GAE or disseminated disease.

Although Balamuthia GAE is often fatal, there are several recorded cases of Balamuthia infection in the United States in which the patient survived after long-term treatment with multiple drugs; a few survivors have also been reported in other countries. All of the U.S. survivors had GAE; some of the survivors had excisional biopsies of one of their multiple brain lesions. At least one survivor had an accompanying cutaneous lesion.  In some of the US cases, the patients were able to return to normal functioning with no reported sequelae. Early diagnosis and treatment might increase the chances for survival.