eMedicine Specialties > Gastroenterology > Liver
Amebic Hepatic Abscesses: Treatment & Medication
Updated: Sep 19, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
Most uncomplicated amebic liver abscesses can be treated successfully with amebicidal drug therapy alone. Use tissue amebicides to eradicate the invasive trophozoite forms in the liver. After completion of treatment with tissue amebicides, administer luminal amebicides for eradication of the asymptomatic colonization state. Failure to use luminal agents can lead to relapse of infection in approximately 10% of patients. In general, metronidazole, tinidazole, emetine, and dehydroemetine are active in invaded tissues; chloroquine is active only in the liver; tetracycline acts on the bowel wall; and diloxanide furoate, paromomycin, and iodoquinol are luminal agents only. The details on tissue and luminal amebicidal agents are discussed in Medication.
- Metronidazole remains the drug of choice for amebic liver abscess. Metronidazole enters the protozoa by passive diffusion and is converted to reactive cytotoxic nitroradicals by reduced ferredoxin or flavodoxin. Tinidazole, another nitroimidazole closely related to metronidazole, was approved for the treatment of amebic liver abscess and invasive amebiasis. Tinidazole is well tolerated by patients. Tinidazole may be administered once daily and appears to be at least as effective as metronidazole, with a clinical cure rate of more than 90%.
- Metronidazole, 750 mg 3 times a day orally for 10 days, was reported to be curative in 90% of patients with amebic liver abscess. The drug also is available for intravenous administration for those patients who are unable to take medication by the oral route.
- Resolution of symptoms is fairly rapid and is observed within 3 days in most of the patients in the United States. In endemic areas outside the United States, it takes relatively longer to resolve symptoms because the abscesses are quite large or multiple by the time patients seek medical attention.
- In vivo resistance to metronidazole by E histolytica has not been reported. Nevertheless, in vitro studies have shown an association between metronidazole resistance and decreased expression of ferredoxin 1 and flavodoxin and increased expression of iron-containing superoxide dismutase and peroxiredoxin in E histolytica.
- Usual adverse effects of metronidazole include nausea, headache, and metallic taste. Abdominal cramps, vomiting, diarrhea, and dizziness also may occur. Dark urine may occur from a metabolite of the drug.
- No randomized controlled trials exist that demonstrate the benefits of combination therapy over monotherapy.
- Outside the United States, other closely related amebicidal agents, such as secnidazole or ornidazole, can be substituted in appropriate dosages. These drugs are not available in the United States.
- Chloroquine phosphate may be substituted or added in the event of failure of resolution of clinical symptoms with metronidazole or another nitroimidazole within 5 days or intolerance to metronidazole or a nitroimidazole. Chloroquine has the disadvantage of being associated with higher relapse rates than nitroimidazoles. Adverse effects include gastrointestinal upset, headache, dizziness, and blurred vision. Retinopathy does not occur at the dose used for amebic liver abscess.
- Emetine or dehydroemetine has a direct lethal action on the trophozoites of E histolytica. These agents are very toxic and, therefore, should be used only as a second-line therapy. Their toxicity includes cardiac arrhythmias, precordial pain, muscle weakness, vomiting, and diarrhea. Dehydroemetine is less toxic than emetine.
- Administer a luminal amebicidal agent to eradicate the intestinal carriage after the amebic liver abscess has been treated with one of the above tissue amebicides. Failure to use luminal agents can lead to relapse of infection in approximately 10% of patients. Luminal agents with proven efficacy include diloxanide furoate, iodoquinol, and paromomycin.
- Diloxanide furoate is free of major adverse effects. The most common adverse effect is flatulence and occasional gastrointestinal upset.
- Iodoquinol (diiodohydroxyquin) rarely causes abdominal pain, diarrhea, or rash. A structurally related diiodohydroxyquin caused subacute myelopticoneuropathy and is obsolete now.
- Although paromomycin may occasionally cause nausea, abdominal cramps, or diarrhea, it is the preferred luminal amebicidal.
- The details on the luminal amebicides are discussed in Medication.
Surgical Care
- Consider therapeutic aspiration of amebic liver abscess in the following situations: (1) high risk of abscess rupture, as defined by cavity size greater than 5 cm; (2) left lobe liver abscess, which is associated with higher mortality and frequency of peritoneal leak or rupture into the pericardium; (3) failure to observe a clinical medical response to therapy within 5-7 days; and (4) cannot differentiate from a pyogenic liver abscess.
- The following are predictive of the need for aspiration: (1) age older than 55 years, (2) abscess greater than 5 cm in diameter, and (3) failure of medical therapy after 7 days.21
- In endemic areas, because of the late presentation and the existence of multiple abscesses, as many as 50% of patients may require aspiration.22
- Routine needle aspiration offers only minimal benefit over medical care alone for uncomplicated amebic liver abscess and, unless one of the above indications exists, should be avoided.23 Prompt medical care decreases the need for aspiration.24
- Imaging-guided needle aspiration and catheter drainage are the procedures of choice. Generally, surgical drainage is not necessary and should be avoided; however, consider open surgical drainage when the abscess is inaccessible to needle drainage or a response to therapy has not occurred in 5-7 days.
- Simple needle aspiration is less invasive, is less expensive, and has the advantage of being able to drain multiple abscesses in the same session. Simple needle aspiration avoids problems related to catheter care (see Procedures).
- Although catheter drainage may be more effective than needle aspiration, in a study by Rajak et al,25 the average time for clinical improvement, mean hospital stay, and time to resolution were similar among the patients who were successfully treated in the 2 treatment groups.
Consultations
- Interventional radiologist for imaging-guided aspiration of the abscess
- General surgeon for open surgical drainage of the abscess under rare circumstances (see Surgical Care)
Diet
No specific diet change or modification is required. However, discuss food hygiene with patients because amebiasis is associated with suboptimal personal or food hygiene. See Deterrence/Prevention.
Activity
- No restriction of activity is needed, except during the first few days of acute illness with pain.
- If emetine or dehydroemetine is used, the patient should remain sedentary for approximately 4 weeks after completing therapy because of their toxicity.
Medication
The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.
Amebicides
Used to eliminate the trophozoites of E histolytica in the liver and bowel wall.
Metronidazole (Flagyl)
Oral synthetic antiprotozoal and antibacterial agent. Effectively eradicates amebic tissue infections, including liver abscess, but is only partially effective against luminal forms. Luminal amebicide also must be used to eradicate bowel luminal infection. Only effective against trophozoites and not cyst forms.
Adult
750 mg PO tid for 10 d
Pediatric
30-50 mg/kg/d PO divided tid for 10 d; not to exceed 500-750 mg/dose
Cimetidine may increase toxicity; may increase effects of anticoagulants; may increase toxicity of lithium and phenytoin; ingestion of ethanol during therapy may induce a disulfiramlike reaction with abdominal cramps, nausea, and emesis
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy; alcoholic beverages should be avoided during administration and for 3 d after; aggravates candidiasis, which may be previously unrecognized; secreted in human milk in concentrations similar to those found in plasma, benefit of using metronidazole in women who are breastfeeding should be weighed against this risk; tumors were increased in rats and mice treated with metronidazole; in elderly patients, monitoring of serum levels may be necessary to adjust dose (plasma clearance is decreased in patients with decreased liver function)
Tinidazole (Tindamax, Fasigyn)
Nitroimidazole derivative used for susceptible protozoal infections. Eradicates amebic tissue infections, including liver abscess, but it is only partially effective against luminal forms. Luminal amebicide must also be used to eradicate bowel luminal infection. Only effective against trophozoites and not cyst forms.
Adult
600 mg PO bid or 800 mg PO tid for 5 d; alternatively, 2 g PO qd for 3-5 d with food
Pediatric
<3 years: Not established
>3 years: 50 mg/kg/d PO for 3-5 d with food; not to exceed 2 g/dose, limited data exist for pediatric patients treated > 3 d (monitor closely)
Limited data exist; interaction information based on experience with other nitroimidazole derivatives (ie, metronidazole); may prolong PT when coadministered with warfarin; avoid alcoholic beverages and preparations containing ethanol or propylene glycol during and 3 d after administration (may cause disulfiramlike reaction); may increase serum levels of lithium, phenytoin, cyclosporine, tacrolimus, and fluorouracil; CYP450 inducers (eg, phenobarbital, rifampin, phenytoin) may increase elimination; CYP450 inhibitors (eg, cimetidine, ketoconazole) may decrease elimination; concurrent administration with cholestyramine may decrease oral bioavailability; oxytetracycline may antagonize effect
Documented hypersensitivity; first trimester of pregnancy
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Carcinogenicity has been observed in mice and rats receiving long-term treatment with metronidazole (another nitroimidazole); although not observed with tinidazole, use cautiously; seizures and peripheral neuropathy have been reported; caution with history of blood dyscrasia; may cause metallic/bitter taste, nausea, anorexia, vomiting, weakness, fatigue, dizziness, or headache; if administered on day of hemodialysis, administer additional dose equivalent to half of recommended dose following dialysis
Dehydroemetine (Dametine)
Preferred agent because it is less toxic than emetine. Eradicates amebic tissue infections, including liver abscess, but does not act on luminal forms. Luminal amebicide also must be used to eradicate the bowel luminal infection. Only effective against the trophozoite forms and not the cyst form. Available in US only from the Parasitic Disease Drug Service, Centers for Disease Control and Prevention (Atlanta, GA 30333; telephone: 404-639-3356).
Adult
1-1.5 mg/kg/d SC/IM qd for 8-10 d; not to exceed 90 mg/kg/d
Pediatric
1-1.5 mg/kg/d SC/IM divided bid for 8-10 d; not to exceed 90 mg/kg/d
None reported
Documented hypersensitivity; cardiac disease, renal disease, recent history of polyneuritis
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution in women who are pregnant and small children; hospitalize when administered because of the potential of serious cardiotoxicity and neuromuscular toxicity; monitor pulse and blood pressure at least tid; perform ECG prior to first injection, on day 5, day 10, and then weekly for 2 wk after last injection; discontinue if resting pulse >110/min, marked hypotension, precordial pain, marked neuromuscular symptoms, T-wave depression, arrhythmias, or proteinuria occur
Emetine (Ipecac)
Eradicates amebic tissue infections, including liver abscess, but does not act on luminal forms. Luminal amebicide also must be used to eradicate the bowel luminal infection. Only effective against the trophozoite forms. Not available in US.
Adult
1 mg/kg/d IM, single daily dose for 8-10 d; not to exceed 65 mg
Pediatric
Administer as in adults, but divide dose bid
None reported
Documented hypersensitivity; cardiac disease, renal disease, recent history of polyneuritis
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution in women who are pregnant and small children; hospitalize when administered because of the potential of serious cardiotoxicity and neuromuscular toxicity; monitor pulse and blood pressure at least tid; perform ECG prior to first injection, on day 5, day 10, and then weekly for 2 wk after last injection; discontinue if resting pulse >110/min, marked hypotension, precordial pain, marked neuromuscular symptoms, T-wave depression, arrhythmias, or proteinuria occur
Iodoquinol (Yodoxin)
Diiodohydroxyquin. Amebicidal against E histolytica and is considered effective against trophozoite and cyst forms. Used to eradicate concurrent intestinal amebiasis in order to prevent recurrence of hepatic amebiasis.
Adult
650 mg PO tid for 20 d
Pediatric
30-40 mg/kg/d PO tid for 20 d; not to exceed 650 mg/dose
None reported
Documented hypersensitivity; hepatic dysfunction
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in thyroid disease; protein-bound serum iodine levels may be increased during treatment, interfering with certain thyroid function tests for as long as 6 mo by increasing serum levels of protein-bound iodine; caution in preexisting optic neuropathy and renal or hepatic disease (other then amebiasis); infants and young children are more susceptible to ocular toxicity (perform ophthalmological examination before and during therapy)
Diloxanide (Entamide, Furamide)
Dichloroacetamide derivative. Amebicidal against trophozoite and cyst forms of E histolytica. Available in US only from the Parasitic Disease Drug Service, Centers for Disease Control and Prevention (Atlanta, GA 30333; telephone: 404-639-3356).
Adult
500 mg PO tid with meals for 10 d; second course of treatment may be repeated after several wk prn
Pediatric
<2 years: Not recommended
>2 years: 20 mg/kg/d PO divided tid for 10 d; second course of treatment may be repeated after several wk prn
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Has not been studied in pregnant women, but
showed no birth defects or other problems in animal studies; adverse GI effects (eg, flatulence, abdominal cramps, nausea, emesis, diarrhea) may occur; esophagitis rarely occurs but should be kept in mind if patient develops retrosternal pain, odynophagia, or dysphagia; not studied in pregnant women (no birth defects or other problems reported in animal studies)
Paromomycin (Humatin)
Amebicidal and antibacterial aminoglycoside active in intestinal amebiasis. Not significantly absorbed from GI tract. Amebicidal against luminal forms.
Adult
30 mg/kg/d PO divided tid for 7 d
Pediatric
25 mg/kg/d PO divided tid for 7 d; not to exceed 2 g/d
Nephrotoxic potential may increase with concurrent administration of other aminoglycosides, penicillins, cephalosporins, amphotericin B, and loop diuretics
Documented hypersensitivity; intestinal obstruction
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Due to narrow therapeutic index and toxic hazards associated with extended administration, not for long-term therapy; caution in renal failure, hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission; adjust dose in renal impairment; caution in ulcerative bowel lesions (inadvertent absorption may occur, resulting in nephrotoxicity)
Chloroquine (Aralen)
Inhibits growth by concentrating within acid vesicles of parasite, which increases internal pH of organism. Also inhibits hemoglobin utilization and metabolism of parasite. In vitro studies with trophozoites of E histolytica demonstrate that chloroquine possesses amebicidal activity comparable to that of emetine. Highly effective in treatment of amebic liver abscess when administered with emetine or dehydroemetine. Like emetine and dehydroemetine, it is not effective against luminal forms.
Irreversible retinal damage does not occur with dose and duration used for treatment of hepatic amebiasis.
Adult
500 mg salt (300-mg base) PO bid for 2 d, followed by 250 mg salt (150-mg base) bid for 2-3 wk
Pediatric
10-mg base/kg/d PO divided bid for 2-3 wk
Cimetidine may increase serum levels (possibly other 4-aminoquinolones); magnesium trisilicate may decrease absorption of 4-aminoquinolones
Documented hypersensitivity; retinal and visual field changes attributable to 4-aminoquinolones; porphyria is considered a contraindication by some authors because drug may exacerbate condition
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; perform periodic ophthalmologic examinations; if any abnormality in visual acuity, visual field, or retinal macular areas (eg, pigmentary changes, loss of foveal reflex) or any visual symptoms (eg, light flashes, streaks) occur, discontinue immediately and closely observe for possible progression; test for muscle weakness; fatalities have been reported following accidental ingestion, sometimes in relatively small doses (0.75-1 g chloroquine phosphate in 3-y-old child); warn to keep this drug out of the reach of children because they are especially sensitive to 4-aminoquinoline compounds
If any severe blood disorder appears that is not attributable to the disease under treatment, discontinue agent unless benefit clearly outweighs risk; potential for serious adverse reactions in breastfeeding infants if chloroquine is administered to breastfeeding women
More on Amebic Hepatic Abscesses |
| Overview: Amebic Hepatic Abscesses |
| Differential Diagnoses & Workup: Amebic Hepatic Abscesses |
 Treatment & Medication: Amebic Hepatic Abscesses |
| Follow-up: Amebic Hepatic Abscesses |
| Multimedia: Amebic Hepatic Abscesses |
| References |
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References
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Further Reading
Keywords
amebic hepatic abscesses, amebic hepatic abscess, amebic liver abscesses, amebic liver abscess, hepatic amebiasis, amebic colitis, Entamoeba histolytica, E histolytica
