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Medication

Medication Summary

To date, the most effective proven therapy remains amphotericin B (intravenous and intrathecal). Eight patients have survived PAM, and nearly all of them received amphotericin B with or without additional agents. One survivor was treated with intravenous and intrathecal miconazole plus rifampin and sulfisoxazole.

One report has described highly effective and selective in vitro activity of voriconazole (Vfend) against N fowleri.^[12]It showed lasting inhibition from concentrations of more than 1 µg/mL. The antiprotozoal drug miltefosine (Miltex) was also tested and found to be amebicidal in serum concentrations of more than 55 µmol. Neither drug is currently recommended in the treatment of PAM, but these preliminary data may lead to in vivo studies or case reports of empirical use.

In conjunction with the FDA, the CDC has an expanded access investigational new drug (IND) protocol in effect with the FDA to make miltefosine 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 Naegleria fowleri and granulomatous amebic encephalitis caused by Balamuthia mandrillaris and Acanthamoeba species.^[11]

Class Summary

Amphotericin B is the most effective drug against N fowleri.

Amphotericin B desoxycholate (Fungizone)

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Polyene antibiotic produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.

Class Summary

Antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Rifampin (Rifadin, Rimactane)

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Inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which in turn blocks RNA transcription.

Follow-up

Hamaty E Jr, Faiek S, Nandi M, Stidd D, Trivedi M, Kandukuri H. A fatal case of primary amoebic meningoencephalitis from recreational waters. Case Rep Crit Care. 2020. 2020:9235794. [QxMD MEDLINE Link]. [Full Text].
Naegleria fowleri — Primary Amebic Meningoencephalitis (PAM) — Amebic Encephalitis. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/parasites/naegleria/index.html. September 24, 2015; Accessed: September 12, 2016.
Fowler M, Carter RF. Acute pyogenic meningitis probably due to Acanthamoeba sp: a preliminary report. Br Med J. 1965 Sep 25. 5464:740-2. [QxMD MEDLINE Link].
Butt CG. Primary amebic meningoencephalitis. N Engl J Med. 1966 Jun 30. 274(26):1473-6. [QxMD MEDLINE Link].
Hebbar S, Bairy I, Bhaskaranand N, et al. Fatal case of Naegleria fowleri meningo-encephalitis in an infant: case report. Ann Trop Paediatr. 2005 Sep. 25(3):223-6. [QxMD MEDLINE Link].
Lozano-Alarcon F, Bradley GA, Houser BS, Visvesvara GS. Primary amebic meningoencephalitis due to Naegleria fowleri in a South American tapir. Vet Pathol. 1997 May. 34(3):239-43. [QxMD MEDLINE Link].
Chu DM, Ferguson TJ, Marciano-Cabral F. Protein kinase activation and protein phosphorylation in Naegleria fowleri amebae in response to normal human serum. J Eukaryot Microbiol. 2000 Jan-Feb. 47(1):40-7. [QxMD MEDLINE Link].
Gharpure R, Gleason M, Salah Z, et al. Geographic range of recreational water-associated primary amebic meningoencephalitis, United States, 1978-2018. Emerg Infect Dis. 2021 Jan. 27 (1):271-4. [QxMD MEDLINE Link]. [Full Text].
Linam WM, Ahmed M, Cope JR, Chu C, Visvesvara GS, da Silva AJ, et al. Successful treatment of an adolescent with Naegleria fowleri primary amebic meningoencephalitis. Pediatrics. 2015 Mar. 135 (3):e744-8. [QxMD MEDLINE Link].
Barnett ND, Kaplan AM, Hopkin RJ, et al. Primary amoebic meningoencephalitis with Naegleria fowleri: clinical review. Pediatr Neurol. 1996 Oct. 15(3):230-4. [QxMD MEDLINE Link].
Investigational Drug Available Directly from CDC for the Treatment of Infections with Free-Living Amebae. MMWR Morb Mortal Wkly Rep. 2013 Aug 23. 62(33):666. [QxMD MEDLINE Link]. [Full Text].
Schuster FL, Visvesvara GS. Free-living amoebae as opportunistic and non-opportunistic pathogens of humans and animals. International Journal for Parasitology. 2004. Vol 34, Issue 9:1001-1027. [Full Text].
Anderson K, Jamieson A. Primary amoebic meningoencephalitis. Lancet. 1972 Apr 22. 1(7756):902-3. [QxMD MEDLINE Link].
Brown RL. Successful treatment of primary amebic meningoencephalitis. Arch Intern Med. 1991 Jun. 151(6):1201-2. [QxMD MEDLINE Link].
CDC. From the Centers for Disease Control. Primary amebic meningoencephalitis--North Carolina, 1991. JAMA. 1992 Aug 19. 268(7):862-3. [QxMD MEDLINE Link].
Cerva L. Laboratory diagnosis of primary amoebic meningo-encephalitis and methods for the detection of limax amoebae in the environment. Folia Parasitol (Praha). 1980. 27(1):1-9. [QxMD MEDLINE Link].
DeNapoli TS, Rutman JY, Robinson JR, Rhodes MM. Primary amoebic meningoencephalitis after swimming in the Rio Grande. Tex Med. 1996 Oct. 92(10):59-63. [QxMD MEDLINE Link].
Duma RJ, Rosenblum WI, McGehee RF, et al. Primary amoebic meningoencephalitis caused by Naegleria. Two new cases, response to amphotericin B, and a review. Ann Intern Med. 1971 Jun. 74(6):923-31. [QxMD MEDLINE Link].
Gustavo dos Santos Neto. Fatal primary amebic meningoencephalitis. A retrospective study in Richmond, Virginia. Am J Clin Pathol. 1970 Nov. 54(5):737-42. [QxMD MEDLINE Link].
Jarolim KL, McCosh JK, Howard MJ, John DT. A light microscopy study of the migration of Naegleria fowleri from the nasal submucosa to the central nervous system during the early stage of primary amebic meningoencephalitis in mice. J Parasitol. 2000 Feb. 86(1):50-5. [QxMD MEDLINE Link].
Primary amebic meningoencephalitis--Arizona, Florida, and Texas, 2007. MMWR Morb Mortal Wkly Rep. 2008 May 30. 57(21):573-7. [QxMD MEDLINE Link].
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 Mar-Apr. 53(2):121-6. [QxMD MEDLINE Link].
Vargas-Zepeda J, Gómez-Alcalá AV, Vásquez-Morales JA, Licea-Amaya L, De Jonckheere JF, Lares-Villa F. Successful treatment of Naegleria fowleri meningoencephalitis by using intravenous amphotericin B, fluconazole and rifampicin. Arch Med Res. 2005 Jan-Feb. 36(1):83-6. [QxMD MEDLINE Link].
Capewell LG, Harris AM, Yoder JS, Cope JR, Eddy BA, Roy SL, et al. Diagnosis, Clinical Course, and Treatment of Primary Amoebic Meningoencephalitis in the United States, 1937-2013. J Pediatric Infect Dis Soc. 2015 Dec. 4 (4):e68-75. [QxMD MEDLINE Link].

Media Gallery

Number of identified cases of primary amoebic meningoencephalitis (PAM), 1937-2007.

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Author

Nicholas John Bennett, MBBCh, PhD, FAAP, MA(Cantab) Assistant Professor of Pediatrics, Co-Director of Antimicrobial Stewardship, Medical Director, Division of Pediatric Infectious Diseases and Immunology, Connecticut Children's Medical Center

Nicholas John Bennett, MBBCh, PhD, FAAP, MA(Cantab) is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics

Disclosure: Received research grant from: Cubist<br/>Received income in an amount equal to or greater than $250 from: Horizon Pharmaceuticals, Shire<br/>Medico legal consulting for: Various.

Coauthor(s)

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa

Disclosure: Received research grant from: Pfizer;GlaxoSmithKline;AstraZeneca;Merck;American Academy of Pediatrics, Novavax, Regeneron, Diassess, Actelion<br/>Received income in an amount equal to or greater than $250 from: Sanofi Pasteur.

Asad A Khan, MD Fellow, Department of Internal Medicine, Division of Infectious Diseases, Louisiana State University Health Science Center

Asad A Khan, MD is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

John W King, MD Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University School of Medicine in Shreveport; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center

John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

J Thomas Cross, Jr, MD, MPH President, A-Cross Medicine Reviews

J Thomas Cross, Jr, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American College of Physicians, Pediatric Infectious Diseases Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

José Rafael Romero, MD Director of Pediatric Infectious Diseases Fellowship Program, Associate Professor, Department of Pediatrics, Combined Division of Pediatric Infectious Diseases, Creighton University/University of Nebraska Medical Center

José Rafael Romero, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, New York Academy of Sciences, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Pediatric Naegleria Medication

Medication Summary

Polyene antibiotics

Class Summary

Amphotericin B desoxycholate (Fungizone)

Amphotericin B desoxycholate (Fungizone)

Antibiotic agents

Class Summary

Rifampin (Rifadin, Rimactane)

Rifampin (Rifadin, Rimactane)

Pediatric Naegleria Medication

Medication Summary

Polyene antibiotics

Class Summary

Amphotericin B desoxycholate (Fungizone)

Amphotericin B desoxycholate (Fungizone)

Antibiotic agents

Class Summary

Rifampin (Rifadin, Rimactane)

Rifampin (Rifadin, Rimactane)

References

Tables

Contributor Information and Disclosures

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