What is the recommended treatment regimen for intestinal amoebiasis caused by Entamoeba histolytica, including first‑line tissue‑active therapy, luminal agents, dosing, and alternatives for pregnancy, children, and metronidazole intolerance?

Treatment of Intestinal Amoebiasis

For intestinal amoebiasis caused by Entamoeba histolytica, treat with metronidazole 750 mg orally three times daily for 5-10 days, followed immediately by a luminal amebicide (paromomycin 25-35 mg/kg/day in three divided doses for 5-10 days) to eliminate intestinal cysts and prevent relapse. 1, 2, 3

First-Line Tissue-Active Therapy

Metronidazole remains the standard tissue amebicide:

• Adults: 750 mg orally three times daily for 5-10 days 1, 2
• Children: 35-50 mg/kg/24 hours divided into three doses for 10 days 2
• Achieves approximately 88% parasitological cure when followed by luminal therapy 1
• Most patients respond within 72-96 hours of initiating treatment 4

Tinidazole is the preferred alternative when metronidazole causes intolerance:

• Adults: 2 g orally once daily for 3 days for intestinal disease 5, 6
• Children >3 years: Approved for use per FDA labeling 6
• Superior tolerability with significantly fewer gastrointestinal side effects compared to metronidazole 5, 7
• Achieves cure rates exceeding 90% 5
• In comparative trials, tinidazole provided 96.5% cure rate versus 55.5% for metronidazole in symptomatic intestinal amebiasis 7

Essential Luminal Amebicide Phase

Critical pitfall: Failure to provide luminal therapy after tissue-active treatment is the most common cause of relapse 4

All patients must receive a luminal amebicide after completing metronidazole or tinidazole, even if stool microscopy becomes negative: 1, 5, 4

Paromomycin (preferred):

• Adults and children: 25-35 mg/kg/day orally in three divided doses with meals for 5-10 days 1, 3
• FDA-approved dosing: 25-35 mg/kg/day for 5-10 days 3

Diloxanide furoate (alternative):

• Adults: 500 mg orally three times daily for 10 days 1, 4
• Not available in all countries

Special Populations

Pregnancy

• Avoid treatment during first trimester 2
• If treatment is absolutely necessary after first trimester, use the 7-10 day metronidazole regimen rather than single-dose therapy, as single-dose results in higher serum levels that reach fetal circulation 2
• Follow with luminal amebicide as in non-pregnant patients 1

Children

• Metronidazole: 35-50 mg/kg/24 hours divided into three doses for 10 days 2
• Tinidazole: Approved for children >3 years of age 6
• Paromomycin: 25-35 mg/kg/day in three divided doses for 5-10 days 3

Metronidazole Intolerance

• Switch to tinidazole 2 g once daily for 3 days 5
• If symptoms persist beyond 72-96 hours, consider adding paromomycin immediately rather than waiting for treatment completion 5
• Still requires luminal amebicide follow-up 5

Treatment Monitoring and Follow-Up

Assess clinical response:

• Expect improvement within 72-96 hours of treatment initiation 4
• If no improvement within 2 days, consider alternative diagnoses or drug resistance 4

Confirm parasitological cure:

• Perform stool examination at least 14 days after completing both treatment phases 1
• Three stool specimens collected on different days should be examined 1

For repeat courses:

• Allow 4-6 weeks interval between courses 2
• Reconfirm presence of trophozoites by appropriate laboratory measures 2
• Obtain total and differential leukocyte counts before and after retreatment 2

Critical Diagnostic Considerations

Before initiating treatment:

• Confirm diagnosis by microscopic examination of fresh feces demonstrating E. histolytica trophozoites 4
• If microscopy unavailable or trophozoites not definitively identified, treat for shigellosis first with ampicillin or TMP-SMX 4
• Do not initiate treatment unless trophozoites are confirmed OR two different antibiotics for shigellosis have failed after 4 days 4
• Distinguish large white cells (nonspecific dysentery indicator) from actual trophozoites to avoid misdiagnosis 4

Common Pitfalls to Avoid

The most critical error is omitting the luminal amebicide phase after tissue-active therapy—this leads to relapse even when stool microscopy appears negative. 5, 4

• Metronidazole and tinidazole alone are ineffective for eliminating luminal cysts due to rapid absorption and short duration 8
• Misdiagnosis between amebic and bacterial dysentery leads to inappropriate treatment 4
• Premature discontinuation before completing both phases increases relapse risk 1