Medication Summary

Asymptomatic amebiasis in nonendemic areas should be treated with a luminal agent (iodoquinol, paromomycin, or diloxanide furoate) to eradicate infection. Asymptomatic Entamoeba dispar infections should not be treated, but education should be pursued.

Amebic colitis is treated first with a nitroimidazole derivative and then with a luminal agent to eradicate colonization. Paromomycin is safe, well tolerated, and effective in the treatment of intestinal amebiasis, including in patients with HIV infection.^[96]Diloxanide is a dichloroacetamide derivative that is amebicidal against trophozoite and cyst forms of E histolytica. It is not available in the United States.

Amebic liver abscess can be cured without drainage by using metronidazole. Treatment with a luminal agent should also follow. Disseminated amebiasis should be treated with metronidazole, which can cross the brain-blood barrier. Empirical antibacterial therapy should be used concomitantly if perforated bowel is a concern.

Class Summary

Several agents are active against anaerobic bacteria and protozoa. Metronidazole is the drug of choice for symptomatic, invasive disease; paromomycin is the drug of choice for noninvasive disease. Because parasites persist in the intestines of 40-60% of patients treated with metronidazole, this drug should be followed with paromomycin to cure luminal infection. Do not give the 2 medications at the same time; the diarrhea that often results from paromomycin might be confused with continuing active intestinal disease from the parasite.

Metronidazole (Flagyl)

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Metronidazole kills trophozoites of Entamoeba histolytica in intestines and tissue but does not eradicate cysts from intestines. It appears to be absorbed into cells. Intermediate metabolized compounds are formed and bind DNA and inhibit protein synthesis, causing cell death. Antimicrobial effect may be due to production of free radicals. Metronidazole is indicated for invasive amebiasis.

Tinidazole (Tinidazole)

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Tinidazole is a 5-nitroimidazole derivative used to treat susceptible protozoal infections. The mechanism by which it acts against Giardia and Entamoeba species is not known. Tinidazole is indicated for treatment of intestinal amebiasis and amebic liver abscess caused by E histolytica in adults and children aged 3 years and older.

Paromomycin

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Paromomycin is an amebicidal and antibacterial aminoglycoside obtained from a strain of Streptomyces rimosus; it is poorly absorbed and is active only against the intraluminal form of amebiasis. Used to eradicate cysts of E histolytica after treatment with metronidazole or tinidazole for invasive disease.

Parasite biochemical pathways are sufficiently different from those of the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Iodoquinol (Yodoxin)

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Iodoquinol is a halogenated hydroxyquinoline that is a luminal amebicide; it acts primarily in the bowel lumen because it is poorly absorbed. It is best tolerated when given with meals. Because iodoquinol is active only against intraluminal form of amebiasis, it is used to eradicate cysts of E histolytica after treatment of invasive disease.

Chloroquine phosphate (Aralen)

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Chloroquine phosphate inhibits growth by concentrating within acid vesicles of the parasite, thereby increasing the organism's internal pH. It also inhibits the organism's hemoglobin utilization and metabolism.

In vitro studies involving trophozoites of E histolytica demonstrate that chloroquine possesses amebicidal activity comparable to that of emetine. It is highly effective in treating amebic liver abscess when administered with emetine or dehydroemetine; however, like emetine and dehydroemetine, it is not effective against luminal forms. Irreversible retinal damage does not occur with the dosage and treatment duration used for treatment of hepatic amebiasis.

Dehydroemetine (Mebadin)

Dehydroemetine is preferred to emetine because it is less toxic. It eradicates amebic tissue infections, including liver abscess, but does not act on luminal forms. To eradicate a bowel luminal infection, a luminal amebicide must be used as well. Dehydroemetine is effective only against trophozoites, not against cysts. In the United States, it is available only from the Parasitic Disease Drug Service of the Centers for Disease Control and Prevention (CDC).

Questions

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Media Gallery

Trichrome stain of Entamoeba histolytica trophozoites in amebiasis. Two diagnostic characteristics are observed. Two trophozoites have ingested erythrocytes, and all 3 have nuclei with small, centrally located karyosomes.
Trichrome stain of Entamoeba histolytica cyst in amebiasis. Each cyst has 4 nuclei with characteristically centrally located karyosomes. Cysts measure 12-15 mm.
Entamoeba histolytica trophozoite. Image courtesy of Centers for Disease Control and Prevention.
Entamoeba histolytica cyst. Image courtesy of Centers for Disease Control and Prevention.
Gross pathology of intestinal ulcers due to amebiasis. Image courtesy of Centers for Disease Control and Prevention.
Histopathology of typical flask-shaped ulcer of intestinal amebiasis. Image courtesy of Centers for Disease Control and Prevention.
Entamoeba histolytica in liver aspirate, trichrome stain. Image courtesy of Centers for Disease Control and Prevention.
Histopathology of amebiasis. Image courtesy of Centers for Disease Control and Prevention.
Life cycle of amebiasis (Entamoeba histolytica). Courtesy of the Centers for Disease Control and Prevention (CDC).

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Author

Vinod K Dhawan, MD, FACP, FRCPC, FIDSA Clinical Professor, Department of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Clinical Professor, Department of Clinical Medicine, Charles R Drew University of Medicine and Science

Vinod K Dhawan, MD, FACP, FRCPC, 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, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Coauthor(s)

Kerry O Cleveland, MD Professor of Medicine, University of Tennessee College of Medicine; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Methodist Healthcare of Memphis

Kerry O Cleveland, MD is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

J Robert Cantey, MD Professor, Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina College of Medicine

J Robert Cantey, MD is a member of the following medical societies: Alpha Omega Alpha, American Society for Clinical Investigation, American Society for Microbiology, Infectious Diseases Society of America, International Society of Travel Medicine, Musculoskeletal Infection Society, Phi Beta Kappa, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Chief Editor

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; Fellow of the Royal College of Physicians, London

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

Disclosure: Nothing to disclose.

Acknowledgements

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 Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation