eMedicine Specialties > Pediatrics: General Medicine > Parasitology
Amebic Meningoencephalitis: Treatment & Medication
Updated: Jan 21, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- Primary amebic meningoencephalitis (PAM)
- Amebic meningitis is seldom diagnosed before an individual's death. Difficulties in diagnosis and rapid progression make this condition extremely difficult to treat. For this reason, aggressively pursue the diagnosis in the patient with CSF findings consistent with bacterial meningitis, with a history of water exposure, and in whom the CSF Gram stain is negative.
- Typically, PAM infection proceeds as an overwhelming acute bacterial meningitis that is unresponsive to routine antibacterials.
- The treatment of choice is amphotericin B, at maximally tolerated doses, with adjunctive rifampin and doxycycline. Successful treatment may also require intrathecal amphotericin B. Sulfisoxazole, phenothiazine, and qinghaosu may have some benefit. Studies have suggested some role for azithromycin as an adjunct to amphotericin B.6,7 More recently, in vitro studies and mouse models of PAM treatment have suggested that miltefosine, chlorpromazine, and rokitamycin may have activity; however, the effectiveness of these treatments remains unproven.
- Granulomatous amebic encephalitis (GAE): Ketoconazole and amphotericin B (alone or in combination) as well as sulfadiazine may be indicated.
Surgical Care
- PAM
- PAM may require the placement of a reservoir for intrathecal amphotericin B or miconazole.
- Hydrocephalus may necessitate shunting.
- GAE
- Biopsy findings may permit diagnosis.
- Excision of solitary or isolated lesions may benefit the individual with GAE.
- Hydrocephalus may necessitate shunting.
Consultations
- Emergent consultations with infectious diseases specialists, neurologists, and neurosurgeons are recommended if PAM or GAE is suspected.
Medication
The goals of pharmacotherapy in patients with amebic meningoencephalitis are to eradicate the infection, prevent complications, and reduce morbidity.
Amebicidal agents
Various amebicidal antibiotics and antifungals are used in combination and at maximal doses and, often, both parenterally and intrathecally. Manage elevated intracranial pressure (ICP) and seizures as necessary. One case report suggested that oral combination therapy for Acanthamoeba meningitis may be successful, but this has not been reproduced.
Amphotericin B (Amphocin, Fungizone)
Amebicidal at low levels. Basis of therapy for all PAM survivors and used for GAE; remains DOC for both in absence of further studies. Although few data are available, use of one of the lipid formulations at maximum doses is recommended because higher doses can be delivered with theoretically less toxicity (see Amphotericin B, lipid-based below).
Adult
Intravenous: 1-1.5 mg/kg/d IV
Intrathecal: 25-100 mcg IT q48-72h; may increase to 500 mcg IT as tolerated
Pediatric
Administer as in adults
Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cyclosporine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor renal, hepatic, electrolyte, and hematologic status closely; hypercalciuria, hypokalemia, hypomagnesemia, renal tubular acidosis, renal failure, acute hepatic failure, hypotension, and phlebitis; common infusion-related reactions include fever, chills, headache, hypotension, nausea, and vomiting; may premedicate with acetaminophen and diphenhydramine 30 min before and 4 h after infusion; meperidine may be useful for chills; hydrocortisone 1 mg/kg (not to exceed 25 mg) may be added to amphotericin B IV bottle, may help prevent immediate adverse reactions; hydrate with 10-15 mL/kg of 0.9% NaCl infused before each dose to minimize risk of nephrotoxicity; consider adjunctive measures as patient's condition tolerates; adjust dose in renal failure
Amphotericin B, lipid-based (Abelcet, AmBisome, Amphotec)
Among the 3 lipid formulations, no data regarding therapeutic efficacy, safety, and dosing for these infections are available. No basis for choosing among them is recognized. Despite lack of data supporting use of these preparations for amebic meningoencephalitis, they are recommended because of dismal outcomes.
Adult
Abelcet or AmBisome: 5 mg/kg/d or more (as tolerated) IV qd infused over at least 2 h
Amphotec: 5-7.5 mg/kg/d IV, not to exceed infusion rate of 1 mg/kg/h
Pediatric
Administer as in adults
Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cyclosporine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Closely monitor renal, hepatic, electrolyte, and hematologic status; hypercalciuria, hypokalemia, hypomagnesemia, renal tubular acidosis, renal failure, acute hepatic failure, hypotension, and phlebitis; common infusion-related reactions include fever, chills, headache, hypotension, nausea, and vomiting; may premedicate with acetaminophen and diphenhydramine 30 min before and 4 h after infusion
Rifampin (Rifadin IV)
Amebicidal activity in vitro and synergistic with amphotericin B when administered IV. Inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription.
Adult
600 mg IV qd
Pediatric
10-20 mg/kg/d IV divided q12-24h; not to exceed 600 mg/d
Induces microsomal enzymes, which may decrease effects of acetaminophen, PO anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, PO contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; BP may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFT findings occur)
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
Obtain CBC counts and baseline clinical chemistries before and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur
Doxycycline (Vibramycin, Doxy)
Amebicidal activity in vitro and is synergistic with amphotericin B when administered IV. Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Adult
200 mg/d IV divided q12h
Pediatric
5 mg/kg/d IV divided q12h; not to exceed 200 mg/d
Tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Documented hypersensitivity; severe hepatic dysfunction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Sulfisoxazole (Gantrisin)
Amebicidal activity in vitro and synergistic with amphotericin B. Sulfonamide derivative that exerts bacteriostatic action by antagonizing PABA, an essential component in folic acid synthesis.
Adult
2 g/d PO divided q12h
Pediatric
1 g/d PO divided q12h
May enhance warfarin effects and hemorrhage can occur; thiopental anesthetic effects may be enhanced; risk of nephrotoxicity may increase when administered concurrently with cyclosporine; serum hydantoin levels may increase when administered concurrently with sulfisoxazole; methotrexate-induced bone marrow suppression may be enhanced when administered concurrently with sulfisoxazole
Coadministration with diuretics may increase incidence of thrombocytopenia with purpura; sulfonamides' free-drug concentration may be increased when administered concurrently with indomethacin; when used concomitantly with methenamine mandelate, sulfonamides may form precipitate in acidic urine; probenecid and salicylates may displace sulfonamides from plasma albumin resulting in increased free-drug concentrations potentiating its toxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Pregnancy category D near term (may cause kernicterus in the newborn); caution in hepatic or renal dysfunction; maintain hydration; fever, rash, hepatitis, systemic lupus erythematosus like syndrome, vasculitis, bone marrow suppression, hemolysis in G-6-PD deficiency, and Stevens-Johnson syndrome
Ketoconazole (Nizoral)
Amebicidal imidazole is DOC for GAE, in combination with amphotericin B. Inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.
Adult
800 mg/d PO divided q12h
Pediatric
3.3-6.6 mg/kg/d PO divided q12h; not to exceed 800 mg/24h
Potent inhibitor of CYP450 3A4; cardiac arrhythmia may occur with cisapride, terfenadine, or astemizole; 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; cisapride, terfenadine recalled from US market, or astemizole recalled from US market use
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
Monitor LFT findings in long-term use; may cause nausea, vomiting, rash, headache, pruritus, or fever
Sulfadiazine (Microsulfon)
Amebicidal activity in vitro and is synergistic with ketoconazole, amphotericin B, or both. Exerts bacteriostatic action by competitive antagonism of PABA.
Adult
4-6 g/d PO divided q6h
Pediatric
100-200 mg/kg/d PO divided q6h
Increases effect of PO anticoagulants and PO hypoglycemic agents; effects are decreased when administered concurrently with PABA or PABA metabolites of drugs (eg, proparacaine, tetracaine, sunscreens, procaine)
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Pregnancy category D near term (may cause kernicterus in the newborn); caution in hepatic or renal dysfunction; maintain hydration; fever, rash, hepatitis, systemic lupus erythematosus like syndrome, vasculitis, bone marrow suppression, hemolysis in G-6-PD deficiency, and Stevens-Johnson syndrome
Azithromycin (Zithromax)
Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected. Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues. Treats mild-to-moderate microbial infections. May have an adjunctive role with amphotericin B to treat GAE/PAM.
Adult
Not established; typical adult dose is 500 mg PO on day 1, then 250 mg/d for days 2-5
Pediatric
Not established; typical pediatric dose is 10-12 mg/kg/d PO
May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Site reactions can occur with IV route; bacterial or fungal overgrowth may result from prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients
More on Amebic Meningoencephalitis |
| Overview: Amebic Meningoencephalitis |
| Differential Diagnoses & Workup: Amebic Meningoencephalitis |
 Treatment & Medication: Amebic Meningoencephalitis |
| Follow-up: Amebic Meningoencephalitis |
| References |
| Further Reading |
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Keywords
amebic meningoencephalitis, acanthamebic keratoconjunctivitis, Acanthamoeba, aphasia, aseptic meningitis, ataxia, bacterial meningitis, Balamuthia mandrillaris, central nervous system infection, CNS infection, cerebral herniation, cranial nerve palsies, diplopia, encephalitis, Entamoeba histolytica, granulomatous amebic encephalitis, GAE, hemiplegias, intracranial pressure, ICP, leptomyxid meningitis, meningitis, myocarditis, Naegleria fowleri, photophobia, primary amebic meningoencephalitis, PAM, Sappinia diploidea
