Amebic Meningoencephalitis Medication

Updated: Oct 12, 2021
  • Author: Linda Nguyen, MD; Chief Editor: Russell W Steele, MD  more...
  • Print
Medication

Medication Summary

Amphotericin B is the drug of choice (DOC) in the treatment of PAM, and should always be used in combination with at least one amebicidal drug. Amphotericin B and/or ketoconazole are among the drugs administered to patients with GAE. Miltefosine is an investigational amebicidal drug provided by the CDC for adjunctive treatment of PAM and GAE.

Next:

Antifungals, Systemic

Class Summary

Various antifungal agents with amebistatic properties are used in combination and at maximal doses, both parenterally and intrathecally. One case report suggested that oral combination therapy for Acanthamoeba meningitis may be successful, but this result has not been reproduced. Azole drugs have been found to have amebicidal properties and are used as adjunctive therapy for both PAM and GAE.

Amphotericin B deoxycholate (Amphotericin B (conventional), Fungizone)

Amphotericin B is amebistatic at low levels. It is the basis of therapy for all PAM survivors and is also used for GAE. This agent remains the DOC for both conditions in the absence of further studies.. Amphotericin B is a polyene antibiotic with poor oral bioavailability. It is produced by a strain of Streptomyces nodosus.   The minimum inhibitory concentration for conventional AMB was 0.1 ug/mL, while liposomal AMB was 10x higher at 1 ug/mL for N. fowleri. Amphotericin B has been shown to be amebistatic as demonstrated by drug efficacy tests.

Amphotericin B, lipid-complex (Abelcet)

Amphotericin B lipid complex consists of amphotericin B complexed with two phospholipids in a 1:1 drug-to-lipid- molar ratio. Among the 3 lipid formulations of amphotericin B, no data regarding their therapeutic efficacy, safety, or dosing for PAM or GAE are available. They have been used with disseminated cutaneous infection.   

Amphotericin B, liposomal (AmBisome)

This is a lipid preparation consisting of amphotericin B within unilamellar liposomes. It delivers higher concentrations of the drug, with a theoretical increase in therapeutic potential and decreased nephrotoxicity.

Amphotericin B is a polyene antibiotic with poor oral availability. It is produced by a strain of Streptomyces nodosus, and it can be fungistatic or fungicidal. The drug binds to sterols (eg, ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human cells may occur via this same mechanism.

Amphotericin B colloidal dispersion (Amphotec)

Amphotericin B colloidal dispersion is a lipid preparation consisting of amphotericin B attached to lipid discoid structures. Amphotericin B is a polyene antibiotic with poor oral availability. It is produced by a strain of Streptomyces nodosus, and it can be fungistatic or fungicidal. The drug binds to sterols (eg, ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human cells may occur via this same mechanism.

Rifampin (Rifadin IV)

Rifampin has amebicidal activity in vitro and is synergistic with amphotericin B when administered intravenously. It inhibits ribonucleic acid (RNA) synthesis in bacteria by binding to the beta subunit of deoxyribonucleic acid (DNA) ̶ dependent RNA polymerase, which, in turn, blocks RNA transcription.

Doxycycline (Vibramycin, Doxy 100, Doryx, Adoxa)

Doxycycline has amebicidal activity in vitro and is synergistic with amphotericin B when administered intravenously. It inhibits protein synthesis and, consequently, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Erythromycin ethylsuccinate-sulfisoxazole (E.S.P.)

The combination of erythromycin and sulfisoxazole is well absorbed from the gastrointestinal (GI) tract but is best administered on a full stomach to avoid GI upset. Erythromycin inhibits bacterial protein synthesis. Sulfisoxazole inhibits the synthesis of folic acid from para-aminobenzoic acid in bacteria.

Ketoconazole

Ketoconazole is an amebicidal imidazole that, in combination with amphotericin B, is the DOC for GAE. It inhibits the synthesis of ergosterol, allowing cellular components to leak and, consequently, causing fungal cell death to occur.

Sulfadiazine

Sulfadiazine has amebicidal activity in vitro and is synergistic with ketoconazole and/or amphotericin B. It exerts bacteriostatic action by competitive antagonism of PABA.

Azithromycin (Zithromax, Zmax)

Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocking the dissociation of peptidyl transfer RNA (tRNA) from ribosomes; this causes RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected. Azithromycin also has known immunomodulatory properties that may confer additional anti-inflammatory benefits.

Azithromycin 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. Azithromycin treats mild to moderate microbial infections. It may have an adjunctive role with amphotericin B in the treatment of GAE/PAM.

Flucytosine (5-FC, 5-fluorocytosine, Ancobon)

Flucytosine is taken up by fungal cells and is converted into 5-fluorouracil (5-FU), which is then converted to metabolites that inhibit fungal RNA and DNA synthesis. Flucytosine has been shown to be effective in the amoebae causing GAE in vitro and can be used as adjunctive therapy for GAE.

Trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Cotrim)

The combination drug has synergy in inhibiting the folate synthesis pathway. Trimethoprim inhibits the dihydrofolate reductase step and sulfamethoxazole inhibits the dihydropteroate synthetase step. This drug works de novo on microbial organisms, including amoebae, and has been used in GAE treatment.

Previous
Next:

Antiparasitic Agents

Pyrimethamine (Daraprim)

Pyrimethamine inhibits folic acid synthesis by inhibiting dihydrofolate reductase and therefore inhibits DNA and RNA synthesis. This drug is effective in many species, including amoebae, and has been used adjunctively in GAE.

Previous
Next:

Antipneumocystis Agents

Pentamidine (NebuPent, Pentam)

The mechanism of Pentamidine is unknown but likely involves the mitochondria. It has been used as adjunctive therapy to treat GAE.

Previous
Next:

Antileishmaniasis Agents

Miltefosine (Impavido)

Miltefosine likely interacts with lipids, including those on cell membranes, inhibits cytochrome c oxidase in mitochondrial function, and leads to cellular apoptosis. Initially studied as a chemotherapeutic agent to treat breast cancer, it was found to be an effective anti-amebic drug. The CDC now offers Miltefosine as an investigational drug in the treatment of PAM and GAE.

Previous