eMedicine Specialties > Infectious Diseases > Parasitic Infections

Acanthamoeba: Treatment & Medication

Author: Nancy F Crum-Cianflone, MD, Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Naval Medical Center at San Diego; HIV Research Physician, Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences
Contributor Information and Disclosures

Updated: Jun 30, 2008

Treatment

Medical Care

Medical therapy for Acanthamoeba infection is not well established. Listed below are treatments that have been reported in the literature.

  • Keratitis
    • Successful treatment of keratitis consists of early diagnosis and aggressive surgical and medical therapies.
    • Medical treatment consists of topical antimicrobial agents, which can achieve high concentrations at the site of the infection.
    • Because the cyst form may be highly resistant to therapy, a combination of agents is generally used.
    • Many authorities recommend a combination of propamidine 0.1%, miconazole nitrate 1%, and neomycin. Others suggest a combination of a diamide (propamidine isethionate) with a cationic antiseptic (polyhexamethylene biguanide [PHMB] or chlorhexidine).
    • These topical antimicrobials are administered every hour immediately after corneal debridement. These agents are then continued hourly during waking hours for 3 days (at least 9 times/day is recommended). The frequency is then reduced to every 3 hours. Two weeks may be required before a response is observed, and the total duration of therapy is a minimum of 3-4 weeks. Some advocate treating for 6-12 months. When therapy is discontinued, close observation is warranted to rule out recurrent disease.
    • No clear consensus exists about use of steroids. Most authorities recommend that steroid use is probably best avoided. Patients receiving steroids should continue antiamebic therapy for several weeks after the steroids are stopped. Rabinovitch and coworkers (1991) showed that steroid use was significantly greater among patients in whom medical therapy failed than in those whose medical therapy was successful.4  A more recent study by Park et al (1997) revealed no difference in response to medical therapy in patients who used topical steroids compared with those who did not. However, in this study, patients treated with topical steroids required longer duration of medical therapy (38.5 wk vs 20 wk).5
  • Granulomatous amebic encephalitis
    • Treatment is not standardized and is limited. Most use a combination of therapies for the treatment of GAE, which should be urgently administered. Antibiotic sensitivity testing should be performed and may help guide therapy.
    • In vitro and in vivo data suggest that the following medications have activity against Acanthamoeba:
      • Ketoconazole, miconazole, itraconazole, fluconazole
      • Pentamidine
      • Amphotericin B
      • Paromomycin
      • Polymyxin
      • Trimethoprim-sulfamethoxazole
      • Sulfadiazine
      • Flucytosine
      • Clotrimazole
      • Rifampin
    • Two immunocompetent children survived with treatment that consisted of ketoconazole, rifampin, and trimethoprim-sulfamethoxazole. A recent case reported discussed the use of this combination, but the patient ultimately relapsed and died of progressive leukemia.6
    • Other potential regimens include (1) fluconazole and sulfadiazine or (2) pentamidine, amphotericin, flucytosine, rifampin, itraconazole, and chlorhexidine.
  • Disseminated disease: A case that involved only the skin was treated with intravenous pentamidine, topical chlorhexidine gluconate, and 2% ketoconazole cream, followed by oral itraconazole.

Surgical Care

  • Keratitis: The abnormal epithelium is débrided. Penetrating keratoplasty may be necessary in cases that do not respond to medical therapy.

Consultations

  • Keratitis
    • Infectious diseases specialist
    • Ophthalmologist
  • Granulomatous amebic encephalitis and disseminated disease
    • Infectious diseases specialist
    • Neurologist

Medication

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

Antifungals

The mechanism of action of these agents may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.


Ketoconazole (Nizoral)

Imidazole broad-spectrum antifungal agent. Inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.

Adult

400 mg PO qd

Pediatric

<2 years: Not established
>2 years: 3.3-6.6 mg/kg/d PO

Isoniazid may decrease bioavailability of ketoconazole; coadministration decreases effects of either rifampin or ketoconazole; may increase effect of anticoagulants; may increase toxicity of corticosteroids and cyclosporine (cyclosporine dosage can be adjusted); may decrease theophylline levels

Documented hypersensitivity; fungal meningitis

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Hepatotoxicity may occur; may reversibly decrease corticosteroid serum levels (adverse effects are avoided with dose of 200-400 mg/d); administer antacid, anticholinergics, or H2-blockers at least 2 h after taking ketoconazole


Itraconazole (Sporanox)

Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Adult

200-400 mg PO qd

Pediatric

Not established

Antacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; may increase tacrolimus and cyclosporine plasma concentrations when high doses are used; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin or simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death; may increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce itraconazole levels (phenytoin metabolism may be altered)

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in hepatic insufficiencies


Pentamidine (Pentam-300, Pentacarinat, NebuPent)

Inhibits growth of protozoa by blocking oxidative phosphorylation and inhibiting incorporation of nucleic acids into RNA and DNA, causing inhibition of protein and phospholipid synthesis.

Adult

4 mg/kg/d IV; dose reduction to 3 mg/kg often is employed after first 3 d to manage toxicity

Pediatric

Administer as in adults

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in diabetes mellitus, hypertension or hypotension, hepatic dysfunction, hypoglycemia, leukopenia, and thrombocytopenia


Flucytosine (Ancobon)

Converted to fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against Candida and Cryptococcus and generally used in combination with amphotericin B.

Adult

100 mg/kg/d PO divided qid

Pediatric

Not established

Amphotericin B may increase toxicity of flucytosine; cytosine may inactivate flucytosine

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in bone marrow suppression; adjust dose in renal impairment

More on Acanthamoeba

Overview: Acanthamoeba
Differential Diagnoses & Workup: Acanthamoeba
Treatment & Medication: Acanthamoeba
Follow-up: Acanthamoeba
References
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References

  1. Schaumberg DA, Snow KK, Dana MR. The epidemic of Acanthamoeba keratitis: where do we stand?. Cornea. Jan 1998;17(1):3-10. [Medline].

  2. Wilhelmus KR, Jones DB, Matoba AY, et al. Bilateral acanthamoeba keratitis. Am J Ophthalmol. Feb 2008;145(2):193-197. [Medline].

  3. Parmar DN, Awwad ST, Petroll WM, et al. Tandem scanning confocal corneal microscopy in the diagnosis of suspected acanthamoeba keratitis. Ophthalmology. Apr 2006;113(4):538-47. [Medline].

  4. Rabinovitch T, Weissman SS, Ostler HB, et al. Acanthamoeba keratitis: clinical signs and analysis of outcome. Rev Infect Dis. Mar-Apr 1991;13 Suppl 5:S427. [Medline].

  5. Park DH, Palay DA, Daya SM, et al. The role of topical corticosteroids in the management of Acanthamoeba keratitis. Cornea. May 1997;16(3):277-83. [Medline].

  6. Gupta D, Panda GS, Bakhshi S. Successful treatment of acanthamoeba meningoencephalitis during induction therapy of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. Jun 2008;50(6):1292-3. [Medline].

  7. Acanthamoeba keratitis in soft-contact-lens wearers. MMWR Morb Mortal Wkly Rep. Jul 3 1987;36(25):397-8, 403-4. [Medline].

  8. Acanthamoeba keratitis multiple states, 2005-2007. MMWR Morb Mortal Wkly Rep. Jun 1 2007;56(21):532-4. [Medline].

  9. Cunha BA. Antibiotic Essentials. 5th ed. Royal Oak, Mich: Physician's Press; 2006.

  10. De Jonckheere JF. Ecology of Acanthamoeba. Rev Infect Dis. Mar-Apr 1991;13 Suppl 5:S385-7. [Medline].

  11. Hammersmith KM. Diagnosis and management of Acanthamoeba keratitis. Curr Opin Ophthalmol. Aug 2006;17(4):327-31. [Medline].

  12. Kaji Y, Hu B, Kawana K, et al. Swimming with soft contact lenses: danger of acanthamoeba keratitis. Lancet Infect Dis. Jun 2005;5(6):392. [Medline].

  13. Lindquiest td. Treatment of Acanthamoeba keratitis. Cornea. 1998;17:11-16.

  14. Marciano-Cabral F, Cabral G. Acanthamoeba spp. as agents of disease in humans. Clin Microbiol Rev. Apr 2003;16(2):273-307. [Medline].

  15. Martinez AJ. Infection of the central nervous system due to Acanthamoeba. Rev Infect Dis. Mar-Apr 1991;13 Suppl 5:S399-402. [Medline].

  16. Mathers WD, Nelson SE, Lane JL, et al. Confirmation of confocal microscopy diagnosis of Acanthamoeba keratitis using polymerase chain reaction analysis. Arch Ophthalmol. Feb 2000;118(2):178-83. [Medline].

  17. Migueles S, Kumar P. Primary cutaneous acanthamoeba infection in a patient with AIDS. Clin Infect Dis. Dec 1998;27(6):1547-8. [Medline].

  18. Nachega JB, Rombaux P, Weynand B, et al. Successful treatment of Acanthamoeba rhinosinusitis in a patient with AIDS. AIDS Patient Care STDS. Oct 2005;19(10):621-5. [Medline].

  19. Oliva S, Jantz M, Tiernan R, et al. Successful treatment of widely disseminated acanthamoebiasis. South Med J. Jan 1999;92(1):55-7. [Medline].

  20. Paltiel M, Powell E, Lynch J, et al. Disseminated cutaneous acanthamebiasis: a case report and review of the literature. Cutis. Apr 2004;73(4):241-8. [Medline].

  21. Schaumberg DA, Snow KK, Dana MR. The epidemic of Acanthamoeba keratitis: where do we stand?. Cornea. Jan 1998;17(1):3-10. [Medline].

  22. Singh U. Free-Living Amebas. Mandell, Douglas, and Bennetts Principles and Practices of Infectious Diseases.

  23. Singhal T, Bajpai A, Kalra V, Kabra SK, Samantaray JC, Satpathy G, et al. Successful treatment of Acanthamoeba meningitis with combination oral antimicrobials. Pediatr Infect Dis J. Jun 2001;20(6):623-7. [Medline].

  24. Sison JP, Kemper CA, Loveless M, et al. Disseminated acanthamoeba infection in patients with AIDS: case reports and review. Clin Infect Dis. May 1995;20(5):1207-16. [Medline].

  25. Slater CA, Sickel JZ, Visvesvara GS, et al. Brief report: successful treatment of disseminated acanthamoeba infection in an immunocompromised patient. N Engl J Med. Jul 14 1994;331(2):85-7. [Medline].

  26. Stapleton F, Seal DV, Dart J. Possible environmental sources of Acanthamoeba species that cause keratitis in contact lens wearers. Rev Infect Dis. Mar-Apr 1991;13 Suppl 5:S392. [Medline].

  27. Sun X, Zhang Y, Li R, et al. Acanthamoeba keratitis: clinical characteristics and management. Ophthalmology. Mar 2006;113(3):412-6. [Medline].

  28. Thebpatiphat N, Hammersmith KM, Rocha FN, et al. Acanthamoeba keratitis: a parasite on the rise. Cornea. Jul 2007;26(6):701-6. [Medline].

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Further Reading

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Keywords

Acanthamoeba, Acanthamoeba castellanii, A castellanii, Acanthamoeba polyphaga, A polyphaga, Acanthamoeba culbertsoni, A culbertsoni, Acanthamoeba palestinensis, A palestinensis, Acanthamoeba astronyxis, A astronyxis, Acanthamoeba hatchetti, A hatchetti, Acanthamoeba rhysodes, A rhysodes, Acanthamoeba divionensis, A divionensis, Acanthamoeba quna, A quna, Acanthamoeba lugdunensis, A lugdunensis, Acanthamoeba griffini, A griffini,Naegleria, Balamuthia, acanthamebic infection, keratitis in contact lens wearers, granulomatous amebic encephalitis, GAE, disseminated disease, free-living amoebas, disseminated granulomatous amebic disease, amebic keratitis, Acanthamoeba keratitis

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Contributor Information and Disclosures

Author

Nancy F Crum-Cianflone, MD, Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Naval Medical Center at San Diego; HIV Research Physician, Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences
Nancy F Crum-Cianflone, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

David Hall Shepp, MD, Program Director, Fellowship in Infectious Diseases, Department of Medicine, North Shore University Hospital; Associate Professor, New York University School of Medicine
David Hall Shepp, MD is a member of the following medical societies: Infectious Diseases Society of America
Disclosure: Gilead Sciences Salary Management position

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine
Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and Massachusetts 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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