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 ^{1, 6, 7}, but was changed in some cases to clarithromycin ¹ 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) ⁸.

^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 ⁹ 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 ^{5–7, 10}. 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.

^d Although miltefosine has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of leishmaniasis, it remains unavailable commercially in the U.S. Therefore, CDC has obtained an expanded access Investigational New Drug (IND) protocol that allows for the storage and release of miltefosine from CDC headquarters in Atlanta, Georgia. If, in consultation with CDC free-living ameba subject matter experts, it is felt that your patient may benefit from miltefosine, arrangements will be made to send a limited supply of miltefosine to your medical center.

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 ^{1–3, 6, 7, 11, 12}; a few survivors have also been reported in other countries ^{5, 13}. 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 ^{1, 5}.  In some of the US cases, the patients were able to return to normal functioning with no reported sequelae ^{2, 11}. Early diagnosis and treatment might increase the chances for survival.

References

1. Deetz TR, Sawyer MH, Billman G, Schuster FL, Visvesvara GS. Successful treatment of Balamuthia amoebic encephalitis: presentation of 2 cases. Clin Infect Dis. 2003;37:1304-12.
2. Jung S, Schelper RL, Visvesvara GS, Chang HT. Balamuthia mandrillaris meningoencephalitis in an immunocompetent patient: an unusual clinical course and a favorable outcome. Arch Pathol Lab Med. 2004;128:466-8.
3. Cary LC, Maul E, Potter C, Wong P, Nelson PT, Given C, Robertson W. Balamuthia mandrillaris meningoencephalitis: survival of a pediatric patient. [PDF – 7 pages] Pediatrics. 2010;125:e699-703.
4. Sanderson L, Dogruel M, Rodgers J, De Koning HP, Thomas SA. Pentamidine movement across the murine blood-brain and blood-cerebrospinal fluid barriers: effect of trypanosome infection, combination therapy, p-glycoprotein, and multidrug resistance-associated protein. J Pharmacol Exp Ther. 2009;329:967–77.
5. Martinez DY, Seas C, Bravo F, Legua P, Ramos C, Cabello AM, Gotuzzo E. Successful treatment of Balamuthia mandrillaris amoebic infection with extensive neurological and cutaneous involvement. Clin Infect Dis. 2010;51:e7-11.
6. CDC. Balamuthia mandrillaris transmitted through organ transplantation — Mississippi, 2009. MMWR Morb Mortal Wkly Rep. 2010;59:1165–70.
7. Orozco LD, Khan MA, Fratkin JD, Hanigan WC. Asymptomatic aneurysm of the cavernous and supraclinoid internal carotid artery in a patient with Balamuthia mandrillaris encephalitis. J Clin Neurosci 2011;18:1118–20.
8. Schuster FL, Visvesvara GS. Opportunistic amebae: challenges in prophylaxis and treatment. Drug Resist Updat. 2004;7:41-51.
9. Schuster FL, Guglielmo BJ, Visvesvara GS. In-vitro activity of miltefosine and voriconazole on clinical isolates of free-living amebas: Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria fowleri. J Eukaryot Microbiol. 2006;53:121-6.
10. Aichelburg AC, Walochnik J, Assadian O, Prosch H, Steuer A, Perneczky G, Visvesvara GS, Aspöck H, Vetter N. Successful treatment of disseminated Acanthamoeba sp. infection with miltefosine. Emerg Infect Dis. 2008;14:1743-6.
11. Healy JF. Balamuthia amebic encephalitis: radiographic and pathologic findings. AJNR Am J Neuroradiol. 2002;23:486-9.
12. CDC. Balamuthia amebic encephalitis – California, 1999-2007. MMWR Morb Mortal Wkly Rep. 2008;57(28):768-71.
13. Doyle JS, Campbell E, Fuller A, Spelman DW, Cameron R, Malham G, Gin D, Lewin SR. Balamuthia mandrillaris brain abscess successfully treated with complete surgical excision and prolonged combination antimicrobial therapy. J Neurosurg. 2011;114:458–62.