Candidiasis in Emergency Medicine Medication
- Author: Tarlan Hedayati, MD; Chief Editor: Rick Kulkarni, MD more...
Medication Summary
Antifungal therapy should be started immediately after necessary cultures have been obtained from all suspected sites of infection.
Significant advances have been made in the treatment of Candida with the development of newer azoles, echinocandins, and lipid formulations of amphotericin B.
Antifungals, azole
Class Summary
Azoles are fungicidal only at very high concentrations. Azoles function by selectively inhibiting the synthesis of an essential component of fungal cell membrane, ergosterol.
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.
Terconazole vaginal (Terazol-3, Terazol-7)
Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased, causing nutrients to leak out, resulting in fungal cell death.
Butoconazole (Femstat-3, Gynazole-1)
Broad-spectrum antifungal agent that inhibit yeast growth by altering cell membrane permeability, which causes fungal cell death.
Use 2% vaginal cream. Available over the counter.
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.
Ketoconazole (Nizoral)
Imidazole broad-spectrum antifungal agent. Nizoral impairs synthesis of ergosterol (the main sterol of fungal cell membranes), allowing increased permeability and leakage of cellular components, causing cell death. Used in treatment of chronic mucocutaneous candidiasis and cutaneous infections.
Itraconazole (Sporanox)
Has fungistatic activity. 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. Effective against broad range of fungi, including Candida species and is indicated for the treatment of cutaneous, oral, esophageal, and disseminated candidiasis.
Available in IV, 100-mg capsules, and oral solution at 10 mg/mL.
Capsules require gastric acidity for absorption and should be taken with food to increase absorption. Liquid formulation increases bioavailability and decreases need for acidity for proper absorption.
Use of solution has been recommended in mucosal and invasive candidiasis, while capsules can be used in onychomycosis and dermatophyte infections.
Miconazole topical (Desenex, Monistat, Micatin)
Inhibits biosynthesis of ergosterol, damaging fungal cell wall membrane, which results in fungal cell death.
Lotion preferred in intertriginous areas; cream must be applied sparingly to avoid maceration effects.
Effective in treating vaginitis and cutaneous infections.
Clotrimazole (Mycelex, Lotrimin, Mycelex Troches)
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.
Tioconazole (Monistat-1, Vagistat-1)
Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased, causing nutrients to leak out, resulting in fungal cell death.
Posaconazole (Noxafil)
Triazole antifungal agent. Blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. Available as oral susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.
Econazole (Spectazole)
Antifungal agent that is a water-miscible base consisting of pegoxol 7 stearate, peglicol 5 oleate, mineral oil, benzoic acid, butylated hydroxyanisole, and purified water. The color of the soft cream is white to off white, and it is for topical use only. Interferes with RNA and protein synthesis and metabolism. Disrupts fungal cell wall permeability, causing fungal cell death. Exhibits broad-spectrum antifungal activity against many gram-negative organisms. Effective in cutaneous infections.
Antifungals, polyenes
Class Summary
Polyenes (nystatin and amphotericin B) bind to ergosterol on the fungal cell membrane and create pores in the membrane resulting in leakage of intracellular proteins thereby destroying the fungal cell.
Amphotericin B, conventional (Amphocin, Fungizone)
Produced from a strain of Streptomyces nodosus. Antifungal activity of amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at sites containing ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large losses of ions and other molecules. A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity of amphotericin B may reside in ability to cause auto-oxidation of cell membranes.
In recent years, lipid formulations have been developed. Total dose needs to be adjusted depending on type of candidal infection being treated. Most patients receive a total dose of 0.5-1.5 g.
Amphotericin B, liposomal (AmBisome)
Novel lipid formulations of amphotericin B that deliver higher concentrations of the drug, with a theoretical increase in therapeutic potential and decreased nephrotoxicity. Produced from a strain of S nodosus. Antifungal activity of amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at sites containing ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large losses of ions and other molecules. A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity of amphotericin B may reside in ability to cause auto-oxidation of cell membranes.
Formulation types include amphotericin B lipid complex (ABLC, Abelcet), amphotericin B colloidal dispersion (ABCD, Amphotec), and liposomal amphotericin B (L-AMB, AmBisome).
ABLC and ABCD approved for treating adults and children with fungal infections refractory to or intolerant of conventional amphotericin B. L-AMB is approved for aspergillosis, candidiasis, and cryptococcosis, and also for patients with neutropenia who have persistent fever on broad-spectrum antibiotics.
Nystatin (Mycostatin)
Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei; effective against various yeasts and yeastlike fungi. Changes permeability of fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak.
Treatment should continue until 48 h after disappearance of symptoms. Used for treatment of oral thrush (although not in patients with AIDS) and cutaneous infections.
Antimetabolite
Class Summary
Flucytosine is given occasionally in combination with amphotericin B for central nervous system infections.
Flucytosine (Ancobon)
Although the exact mode of action is unknown, it is proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism where it is converted to 5-fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against Candida and Cryptococcus species and generally used in combination with amphotericin B.
Use in combination with another agent because acquired resistance develops frequently when flucytosine is administered alone.
Well absorbed orally but should be administered IV to critically ill patients.
Antifungals, Echinocandins
Class Summary
Echinocandins have potent fungicidal activity against Candida species and have successfully treated Candida resistant to azoles. These drugs are not metabolized through the CYP450 system. They act by inhibiting the synthesis of an essential cell wall component that is not present in mammalian cells.
Caspofungin (Cancidas)
FDA approved to treat candidemia, invasive candidiasis, and esophageal candidiasis. A glucan synthesis inhibitor that inhibits synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall. Caspofungin has demonstrated activity against C albicans, C glabrata, C guilliermondii, C krusei, C parapsilosis, and C tropicalis. Activity against C parapsilosis may only be fungistatic. Response rate has been demonstrated to be 73% for caspofungin as compared to 62% for amphotericin B.
Micafungin (Mycamine)
Member of new class of antifungal agents, echinocandins, that inhibit cell wall synthesis. Inhibits synthesis of 1,3-beta-D-glucan, an essential fungal cell wall component not present in mammalian cells.
Indications include (1) prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation and (2) treatment of esophageal candidiasis.
Anidulafungin (Eraxis)
Antifungal agent of the echinocandin class. Inhibits synthesis of 1,3-beta-D-glucan, an essential component of fungal cell walls. Indicated to treat esophageal candidiasis, candidemia, and other forms of candidal infections (eg, intraabdominal abscesses, peritonitis).
Antifungal Agents, Allylamine
Class Summary
These are fungicidal agents.
Terbinafine (Daskil, Lamisil)
Inhibits squalene epoxidase, which decreases ergosterol synthesis, causing fungal-cell death.
Use medication until symptoms significantly improve.
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