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Naegleria Infection Treatment & Management

  • Author: Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, DSc; Chief Editor: Mark R Wallace, MD, FACP, FIDSA  more...
 
Updated: Nov 23, 2015
 

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 was treated with intravenous and intrathecal amphotericin B, intravenous and intrathecal miconazole, and oral rifampin. The patient survived with minimal neurologic sequelae.[22] In addition, the most recent survivor from India, a 25-day-old boy, was successfully treated with the regimen comprising of amphotericin B, rifampicin, and fluconazole for 4 weeks, along with ventriculoperitoneal shunt for obstructive hydrocephalous. The child was free of neurological sequelae at 8-month of follow-up.[1]

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.

Other drugs that have been evaluated for the treatment of meningoencephalitis due to Naegleria species are miltefosine and chlorpromazine. Kim et al studied the effect of these 2 agents on N fowleri both in vitro as well as in vivo in mice models and compared them with the therapeutic effect of amphotericin B. Chlorpromazine was found to have the best therapeutic activity against Naegleria, both in vitro and in vivo.[37]

In conjunction with the FDA, the CDC has an expanded access investigational new drug (IND) protocol in effect 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 N fowleri and granulomatous amebic encephalitis caused by B mandrillaris and Acanthamoeba species.[38]

Owing to the increasing number of cases being reported and the controversial efficacy of amphotericin B, active research is being carried out to identify newer drugs that are more effective with fewer adverse effects. Recently by using high throughput screening, Debnath et al have identified a novel macrolide, corifungin, with higher activity against Naegleria than amphotericin B. By using in vitro and in vivo animal studies, the authors have demonstrated the superiority of corifungin over amphotericin B. Based on these results, corifungin has been given an orphan drug status by the US Food and Drug Administration for the treatment of PAM.[39]

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Surgical Care

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

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Consultations

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

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Contributor Information and Disclosures
Author

Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, DSc Director-Professor of Microbiology, Head of Department of Microbiology, Jawaharlal Institute, Postgraduate Medical Education and Research, India

Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, DSc is a member of the following medical societies: Royal College of Pathologists, Indian Society for Parasitology, Indian Medical Association, National Academy of Medical Sciences (India), Indian Association of Medical Microbiologists, Indian Association of Biomedical Scientists, Indian Association of Pathologists and Microbiologists, Indian Academy of Tropical Parasitology

Disclosure: Received salary from Jawaharlal Institute of Postgraduate Medical education & Research , Pondicherry , India for employment.

Coauthor(s)

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Thomas M Kerkering, MD Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

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, Wilderness Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Mark R Wallace, MD, FACP, FIDSA Clinical Professor of Medicine, Florida State University College of Medicine; Clinical Professor of Medicine, University of Central Florida College of Medicine

Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, Florida Infectious Diseases Society

Disclosure: Nothing to disclose.

Additional Contributors

Daniel R Lucey, MD, MPH, MD, MPH 

Daniel R Lucey, MD, MPH, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians

Disclosure: Nothing to disclose.

Acknowledgements

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.

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Hematoxin and eosin (H&E)-stained photomicrograph (125X) that shows the cytoarchitectural histopathology found in a case of primary amoebic meningoencephalitis (PAM), caused by Naegleria gruberi. Courtesy of the US Centers for Disease Control and Prevention and Dr. George R. Healy.
 
 
 
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