Medication Summary
The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.
Antifungals
Class Summary
The mechanism of action of these agents may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.
Ketoconazole
Imidazole broad-spectrum antifungal agent. Inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.
Itraconazole (Sporanox, Onmel)
Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Pentamidine (Pentam)
Inhibits growth of protozoa by blocking oxidative phosphorylation and inhibiting incorporation of nucleic acids into RNA and DNA, causing inhibition of protein and phospholipid synthesis.
Flucytosine (Ancobon)
Converted to fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against Candida and Cryptococcus and generally used in combination with amphotericin B.
Clotrimazole
Nonabsorbable imidazole. Broad-spectrum synthetic antifungal agent that inhibits growth of yeasts and fungal growth by altering cell membrane permeability, which causes fungal cell death.
Therapy is directed at the underlying condition, with the goal of minimizing symptoms and preventing complications.
Voriconazole (Vfend)
Available in oral and parenteral forms. FDA approved for esophageal candidiasis and candidemia. Used clinically for serious candidal infections refractory to amphotericin B. Voriconazole has been found to be active against C glabrata and C krusei, as well as isolates that have developed resistance to fluconazole.
Miconazole oral (Oravig)
Inhibits biosynthesis of ergosterol, damaging fungal cell wall membrane, which results in fungal cell death.
Fluconazole (Diflucan)
Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Available as tablets for oral administration, as a powder for oral suspension, and as a sterile solution for IV use. Has fewer adverse effects and better tissue distribution than older systemic imidazoles. Daily dose varies with indication.
Fluconazole penetrates the cerebrospinal fluid, kidneys, and liver well. It is concentrated and excreted by the kidneys in its active form so is effective against urinary tract infections.
Antiparasitic Agents
Class Summary
Biochemical pathways in the parasite are sufficiently different from those in the human host to allow selective interference by chemotherapeutic agents in relatively small doses.
Miltefosine (Impavido)
Developed as an anti-leishmanial therapy, it appears to have some activity and has been used successfully in a number of cases of GAE. It can be orally administered and has mild to moderate gastrointestinal side effects as major toxicity.
Antibiotics
Class Summary
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Sulfadiazine
Through a competitive antagonism of para-aminobenzoic acid (PABA), this agent interferes with microbial growth. It is commonly used for meningococcal prophylaxis.
Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS)
Trimethoprim-sulfamethoxazole inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. One double-strength tablet contains trimethoprim (TMP) 160 mg and sulfamethoxazole (SMX) 800 mg.
Rifampin (Rifadin)
Also called rifampicin. Inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription.
Polymyxin B
Causes leakage of intracellular components by binding to phospholipids, altering permeability and damaging the bacterial cytoplasmic membrane.
Antiseptics
Class Summary
These agents inhibit growth of gram-positive and gram-negative bacteria.
Chlorhexidine topical (Betasept, Hibiclens, Dyna-Hex 2)
Binds to negatively charged bacterial cell walls and extramicrobial complexes. It has bacteriostatic and bactericidal effects.
