eMedicine Specialties > Infectious Diseases > CNS Infections

Naegleria Infection: Treatment & Medication

Author: Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, Director-Professor of Microbiology, Head of Department of Microbiology, Jawaharlal Institute, Postgraduate Medical Education and Research, India
Coauthor(s): Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Barnett Gibbs, MD, Assistant Chief, Department of Clinical Trials, Walter Reed Army Institute of Research, Infectious Disease Service, National Capital Consortium; Assistant Professor of Medicine, Uniformed Services University of the Health Sciences; Diane H Johnson, MD, Assistant Director, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Winthrop-University Hospital, State University of New York at Stony Brook School of Medicine
Contributor Information and Disclosures

Updated: Aug 3, 2009

Treatment

Medical Care

Early diagnosis, treatment, and aggressive supportive care hold the only chance for survival in patients with primary amebic meningoencephalitis (PAM). Very few survivors have been reported, with probably no more than a dozen survivors of an estimated 200 cases.

The best described and authenticated case of successful treatment of PAM involved a 9-year-old girl who was diagnosed early in the disease course and treated with intravenous and intrathecal amphotericin B, intravenous and intrathecal miconazole, and oral rifampin. The patient survived with minimal neurologic sequelae.14

The variables in determining the survival likelihood include how early the diagnosis is made and treatment initiated, the infectious dose of amebae, the virulence of the infecting strain, and the health of the patient.

Naegleria species are highly sensitive to the antifungal drug amphotericin B, and it has been used as the core antimicrobial in virtually all cases in which recovery occurred. Minimum amebacidal concentrations of amphotericin B were determined to be 0.02–0.078 µg/mL. Ultrastructural examination of amebae treated with amphotericin B revealed membrane distortions, including the nuclear envelope, rough and smooth endoplasmic reticula, and plasma membrane blebbing.

The macrolide antibiotic azithromycin is effective against Naegleria species in vitro and in murine models, but it has been reported to have poor CSF penetrance. Other antimicrobials that have been tested, mostly in vitro, include clotrimazole, itraconazole, fluconazole, and ketoconazole, with varying degrees of efficacy. Differences in reported drug sensitivities are due to the use of different N fowleri strains in different laboratories, which show variation to drugs. However, amphotericin B remains the drug of choice in the treatment of PAM.

Surgical Care

Upon evidence of increased intracranial pressure and possible herniation, emergent consultation with a neurosurgeon is warranted for ventriculostomy.

Consultations

Consult with an infectious disease specialist early in the course of illness.

Medication

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.

Amphotericin B offers the only clear evidence for a survival benefit in the treatment of primary amebic meningoencephalitis (PAM).

Antifungals

The mechanism of action usually involves inhibiting pathways (enzymes, substrates, transport) necessary for sterol/cell membrane synthesis or altering the permeability of the cell membrane (polyenes) of the fungal cell.


Amphotericin B (Amphocin, Fungizone)

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.

Adult

25-300 mcg IT q48-72h and increase to 500 mcg as tolerated; alternatively, 0.25-1.5 mg/kg/d IV

Pediatric

25-100 mcg IT q48-72h and increase to 500 mcg as tolerated; alternatively, 0.5-0.7 mg/kg/d IV

Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the risk of renal toxicity is increased with cyclosporine

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC, and hemoglobin concentrations; resume the therapy at the lowest level (eg, 0.25 mg/kg) when the therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock

More on Naegleria Infection

Overview: Naegleria Infection
Differential Diagnoses & Workup: Naegleria Infection
Treatment & Medication: Naegleria Infection
Follow-up: Naegleria Infection
Multimedia: Naegleria Infection
References
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References

  1. Schuster FL. Cultivation of pathogenic and opportunistic free-living amebas. Clin Microbiol Rev. Jul 2002;15(3):342-54. [Medline].

  2. Centers for Disease Control and Prevention (CDC). Primary amebic meningoencephalitis--Arizona, Florida, and Texas, 2007. MMWR Morb Mortal Wkly Rep. May 30 2008;57(21):573-7. [Medline].

  3. Parija SC, Jayakeerthee SR. Naegleria fowleri: a free living amoeba of emerging medical importance. J Commun Dis. Sep 1999;31(3):153-9. [Medline].

  4. Cervantes-Sandoval I, Serrano-Luna Jde J, García-Latorre E, Tsutsumi V, Shibayama M. Mucins in the host defence against Naegleria fowleri and mucinolytic activity as a possible means of evasion. Microbiology. Dec 2008;154(Pt 12):3895-904. [Medline].

  5. Jung SY, Kim JH, Song KJ, Lee YJ, Kwon MH, Kim K. Gene silencing of nfa1 affects the in vitro cytotoxicity of Naegleria fowleri in murine macrophages. Mol Biochem Parasitol. May 2009;165(1):87-93. [Medline].

  6. Factsheet of Naeglaria fowleri. Available at http://www.cdc.gov/ncidod/dpd/parasites/Naegleria/factsht_naegleria.htm.

  7. Jamerson M, Remmers K, Cabral G, Marciano-Cabral F. Survey for the presence of Naegleria fowleri amebae in lake water used to cool reactors at a nuclear power generating plant. Parasitol Res. Apr 2009;104(5):969-78. [Medline].

  8. Naegleria fowleri. Wikipedia. Available at http://en.wikipedia.org/wiki/Naegleria_fowleri. Accessed 9/25/2008.

  9. Parija SC. Amoebae. In: Textbook of Medical Parasitology: Protozoology & Helminthology. 3rd ed. New Delhi, India: All India Publishers and Distributors; 2006:26-61.

  10. Rai R, Singh DK, Srivastava AK, Bhargava A. Primary amebic meningoencephalitis. Indian Pediatr. Dec 2008;45(12):1004-5. [Medline].

  11. Réveiller FL, Cabanes PA, Marciano-Cabral F. Development of a nested PCR assay to detect the pathogenic free-living amoeba Naegleria fowleri. Parasitol Res. May 2002;88(5):443-50. [Medline].

  12. Marciano-Cabral F, MacLean R, Mensah A, LaPat-Polasko L. Identification of Naegleria fowleri in domestic water sources by nested PCR. Appl Environ Microbiol. Oct 2003;69(10):5864-9. [Medline].

  13. Johnson PE, Deromedi AJ, Lebaron P, Catala P, Havens C, Pougnard C. High throughput, real-time detection of Naegleria lovaniensis in natural river water using LED-illuminated Fountain Flow Cytometry. J Appl Microbiol. Sep 2007;103(3):700-10. [Medline].

  14. 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. Jan-Feb 2005;36(1):83-6. [Medline].

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Further Reading

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Keywords

Naegleria fowleri, Naegleria infection, N fowleri, primary amebic meningoencephalitis, PAM, purulent meningoencephalitis, N fowleri meningoencephalitis, Naegleria fowleri meningoencephalitis, Naegleria australiensis, Naegleria italica, Naegleria philippinensis, N australiensis, N italica, N philippinensis

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Contributor Information and Disclosures

Author

Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, Director-Professor of Microbiology, Head of Department of Microbiology, Jawaharlal Institute, Postgraduate Medical Education and Research, India
Subhash Chandra Parija, MBBS, MD, PhD, FRCPath is a member of the following medical societies: Indian Academy of Tropical Parasitology, Indian Association of Biomedical Scientists, Indian Association of Medical Microbiologists, Indian Association of Pathologists and Microbiologists, Indian Medical Association, Indian Society for Parasitology, National Academy of Medical Sciences, India, and Royal College of Pathologists
Disclosure: Jawaharlal Institute of Postgraduate Medical education & Research , Pondicherry , India Salary Employment

Coauthor(s)

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

Barnett Gibbs, MD, Assistant Chief, Department of Clinical Trials, Walter Reed Army Institute of Research, Infectious Disease Service, National Capital Consortium; Assistant Professor of Medicine, Uniformed Services University of the Health Sciences
Disclosure: Nothing to disclose.

Diane H Johnson, MD, Assistant Director, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Winthrop-University Hospital, State University of New York at Stony Brook School of Medicine
Diane H Johnson, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Women's Association, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Daniel R Lucey, MD, MPH, Chief, Fellowship Program Director, Department of Internal Medicine, Division of Infectious Diseases, Washington Hospital Center; Professor, Department of Internal Medicine, Uniformed Services University of the Health Sciences
Daniel R Lucey, MD, MPH is a member of the following medical societies: Alpha Omega Alpha and American College of Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Thomas M Kerkering, MD, Chief of Infectious Diseases, Virginia Tech, Carilion School of Medicine, Roanoke, Virginia
Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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