Medication Summary

The goal of pharmacotherapy is either to terminate the infection when possible or to control the infection and to reduce morbidity when cure is not possible.

Class Summary

The mechanism of action of antifungal agents differs by agent and may involve an alteration of RNA or DNA, allow for an intracellular accumulation of peroxide that is toxic to the fungal cells, or allow for intracellular potassium to be lost while intracellular sodium levels increase.

Amphotericin B (Amphocin, Fungizone)

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Because of its rapid onset of action, this is the DOC for cryptococcal meningitis. Antifungal activity results from its ability to insert itself into fungal cytoplasmic membrane at sites that contain ergosterol or other sterols. Aggregates accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm are produced in cytoplasmic membrane, leading to large losses of ions and other molecules. A second effect is its ability to cause auto-oxidation of cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity may reside in its ability to cause auto-oxidation of cell membranes.

If therapy is supplemented by oral flucytosine, therapy can be used until the patient is afebrile and alert and spinal fluid cultures are negative for 2 wk; then, patient can be placed on fluconazole.

Flucytosine (Ancobon)

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Metabolized to fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against some Candida and Cryptococcus species and generally used in combination with amphotericin B. Always use with another active antifungal agent (eg, amphotericin B).

Fluconazole (Diflucan)

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An antifungal agent active against many yeast and dimorphic fungi. In general, has poor activity against molds and filamentous fungi. Selectively inhibits fungal cytochrome P-450 and sterol C-14-alpha demethylation.

Follow-up

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Media Gallery

Axial T2-weighted magnetic resonance image shows clustered hyperintensities in the left caudate; these are consistent with enlarged Virchow-Robin spaces caused by small cryptococcomas.

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Author

Pradeep Kumar Mada, MD, MRCP(UK) Consulting Physician in Infectious Diseases, Comanche County Memorial Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

John W King, MD Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University School of Medicine in Shreveport; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center

John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Jeffrey D Band, MD, FACP, FIDSA Professor of Medicine, Oakland University William Beaumont School of Medicine; Health System Chair, Healthcare Epidemiology and International Medicine, Beaumont Health System; Former Chief of Infectious Diseases, Beaumont Hospital; Clinical Professor of Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Meredith L DeWitt, MD Fellow, Department of Internal Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center

Meredith L DeWitt, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Folusakin O Ayoade, MD Assistant Professor of Clinical Medicine, Division of Infectious Diseases, Department of Medicine, University of Miami, Leonard M Miller School of Medicine; Attending Physician in Infectious Diseases, Jackson Health System; Attending Physician in Infectious Diseases, University of Miami Hospital

Folusakin O Ayoade, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Medical Association, Infectious Diseases - International Research Initiative, Infectious Diseases Society of America

Disclosure: Nothing to disclose.