eMedicine Specialties > Emergency Medicine > Infectious Diseases
Candidiasis: Treatment & Medication
Updated: Apr 28, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Emergency Department Care
Mucocutaneous candidiasis is often encountered and treatment initiated in the emergency department. Systemic infections in patients with risk factors for Candida infection should be admitted to the hospital and cultures taken prior to initiating antimicrobial therapy
Other treatment of candidiasis
- Generally, the echinocandin class of antifungals should be used as the first-line treatment of candidemia (ie, the critically ill patients or patients with prior azole treatment). There is already a report of echinocandin resistance after long-term therapy for candidemia.19
- Polyenes should not be used to treat patients who have renal failure, and echinocandins and azoles should not be used in patients with severe liver disease because of their respective side effect profiles and pharmacokinetic properties.20
- Mucocutaneous infection typically responds to topical therapy. Nystatin is the least expensive option for oral thrush, but patients frequently complain of its bitter taste. Clotrimazole troches are as effective and less bitter. Proper denture cleansing and care are important measures against oral candidiasis.
- Topical therapy is first line for esophageal candidiasis, but systemic therapy is typically required.
- Intertrigo and diaper rash respond to decreased moisture around the skin. Nystatin powder or cream is used with the addition of a topical steroid for diaper rash.
- Uncomplicated vulvovaginal candidiasis treatment includes many options of topical or oral therapy. Recurrent candidal vaginitis requires a prolonged course of oral medication; probiotic Lactobacillus may help in facilitating treatment of this disease.21
- Invasive candidiasis typically requires parenterally administered antifungal therapy.
- Candida endocarditis frequently requires both medical and surgical therapy. Valve replacement and vegetation removal is often necessary. Antifungal therapy is typically continued for 6-10 weeks parenterally.
- CNS candidal infection can often successfully be treated without intrathecal instillation.
- Peritoneal candidal infection secondary to peritoneal dialysis may respond to peritoneal infusion of antifungal agents in dialysate fluid.
- Candida keratitis may require corneal grafting if not responsive to treatment.
- Full-term infants with Candida amnionitis typically respond to topical therapy. Premature infants frequently require systemic antifungal agents and have a poorer prognosis.
- Endophthalmitis may require vitrectomy and direct intravitreal antifungal instillation.
Consultations
- Infectious disease specialists are typically involved in cases of invasive candidiasis.
- Gastroenterologists typically perform diagnostic endoscopy.
- Surgical drainage may be required with organ involvement and abscess formation.
- Orthopedic surgeons are involved in the management of osteomyelitis and intra-articular infections.
- Cardiothoracic surgeons are frequently necessary in the treatment of endocarditis.
- Ophthalmologic consultation should be obtained on all patients with candidemia to exclude evidence of ocular involvement.
Medication
- 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
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.
Adult
Oropharyngeal and esophageal disease: 100 mg/d PO/IV for 7-14 d
Candidemia and invasive candidiasis: 800-mg loading dose, followed by 400 mg/d PO/IV; if C glabrata, dose should be 800 mg/d
Renal insufficiency:
CrCl 25-49 mL/min: Decrease dose by 50%
CrCl <25 mL/min: Decrease dose by additional 75%
Hemodialysis: Usual daily dose after each dialysis
Bone marrow transplant: 200-400 mg/d PO/IV starting at time of bone marrow ablation and continuing until neutropenia resolves; recent studies seem to indicate continuing therapy for longer periods of time may decrease mortality in transplant recipients
Pediatric
Candidemia: 10-12 mg/kg/d PO/IV loading dose followed by 4.5-6 mg/kg/d PO/IV
CYP450 2C19 and 3A4 inhibitor; levels may increase with hydrochlorothiazide; fluconazole levels may decrease with long-term coadministration of rifampin; may increase concentrations of theophylline, phenytoin, tolbutamide, cyclosporine, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration
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
Adjust dose for renal insufficiency; closely monitor if rashes develop, and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) when taken with underlying medical conditions (eg, AIDS, malignancy) or while taking multiple concomitant medications; not recommended for breastfeeding mothers; QT prolongation and torsade de pointes can occur; rarely, anaphylactic reactions, Stevens-Johnson syndrome, and toxic necrolysis can occur
Convenience and efficacy of single-dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with oral fluconazole versus intravaginal agents
Terconazole (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.
Adult
Vaginal candidiasis:
80-mg tab: Insert 1 suppository (2.5 g) intravaginally hs for 3 d
0.4% cream: Insert 1 applicatorful (5 g) intravaginally hs for 7
Pediatric
Not established
None reported
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
If sensitivity or chemical irritation occurs, discontinue use; use only externally; avoid contact with eyes
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.
Adult
Vaginal candidiasis: Insert 1 applicatorful (5 g) intravaginally hs for 3 d
Pediatric
Not established
None reported
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
If sensitivity or chemical irritation occurs, discontinue use; use only externally; avoid contact with eyes
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.
Adult
Loading dose: 6 mg/kg IV q12h infused over 2 h for 2 doses
Maintenance: 4 mg/kg IV q12h infused over 2 h, when able to tolerate PO may switch to 200 mg PO q12h
Note: For inadequate response, may increase to 300 mg PO q12h; <40 kg administer oral maintenance dose of 100 mg PO q12h (may increase to 150 mg PO q12h)
Pediatric
Not established
CYP450 2C19 (highest affinity), 2C9, and 3A4 (minor) substrate and inhibitor; CYP450 inducers (eg, rifampin) have shown to decrease steady-state peak plasma levels by up to 93%; may increase serum levels of drugs metabolized by CYP450 2C19 or 2C9, of which some are contraindicated (eg, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids), others may need more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG-CoA inhibitors, benzodiazepines, calcium channel blockers)
Documented hypersensitivity; do not administer IV form with CrCl <50 mL/min (decreased excretion of IV vehicle); coadministration with rifampin, rifabutin, carbamazepine, barbiturates, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Decrease maintenance dose with hepatic dysfunction; common adverse effects include visual disturbances, fever, rash, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, rash (including Stevens-Johnson syndrome and phototoxicity), and respiratory disorder; rare cases of severe hepatotoxicity have been reported; administer PO 1 h ac or pc
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.
Adult
Mucocutaneous infections: 400 mg PO qd (with food) for 3-9 mo
Cutaneous infections: Apply topically qd for 14 d
Pediatric
Mucocutaneous infections:
<2 years: Not recommended
>2 years: 5 mg/kg/d PO once; not to exceed 800 mg qd
Isoniazid may decrease bioavailability; coadministration of rifampin may decrease effects of either; may increase effect of anticoagulants; may increase toxicity of corticosteroids and cyclosporine (cyclosporine dosage can be adjusted); may decrease theophylline levels
Documented hypersensitivity; fungal meningitis
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
Hepatotoxicity may occur; may reversibly decrease corticosteroid serum levels (adverse effects avoided with dose of 200-400 mg/d); administer antacid, anticholinergics, or H2-blockers at least 2 h after taking ketoconazole
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.
Adult
Cutaneous candidiasis and onychomycosis: 200 mg PO bid for 7 d/mo for 3-6 mo
Oropharyngeal and esophageal candidiasis: 200 mg/d PO for 7-14 d
Candidemia and invasive candidiasis: 200 mg PO tid for 3 d, followed by 200 mg bid for 14-21 d
Pediatric
Cutaneous candidiasis: 3-5 mg/kg/d PO for 30 d
Antacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin or simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death
Monitoring of liver enzymes recommended; potent inhibitor of CYP3A4 (may increase plasma concentrations of terfenadine, midazolam, cyclosporin, cisapride, quinidine, atorvastatin, simvastatin, lovastatin when coadministered); CYP3A4 inducers, such as phenytoin, rifampin, and isoniazid, may decrease itraconazole concentrations
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
Caution in hepatic insufficiency
Miconazole (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.
Adult
Vaginitis: 200 mg vaginal tab (1 qd for 3 d) or 2% cream (5 g) qd hs for 7 d
Cutaneous infections: Apply topically tid/qid for 7-14 d
Pediatric
<12 years: Not recommended
>12 years: Administer as in adults
None reported
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
If sensitivity or chemical irritation occurs, discontinue use; use only externally; avoid contact with eyes
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.
Adult
OPC: 10-mg troche to be dissolved in the mouth 5 times per d for 7 d
Cutaneous candidiasis: Apply 1% cream, lotion, or solution bid/tid
Vaginal candidiasis: 100-mg pessaries qd for 6 d; 1 applicatorful intravaginally of 1%, 2%, or 10% cream qhs
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Not for treatment of systemic fungal infections; avoid contact with the eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy
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.
Adult
Vaginal candidiasis: Insert 1 applicatorful intravaginally prior to hs
Pediatric
Not established
None reported
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
If sensitivity or chemical irritation occurs, discontinue use; use only externally; avoid contact with eyes
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.
Adult
200 mg (5 mL) PO tid with food or liquid nutritional supplement to enhance absorption
Pediatric
<13 years: Not established
>13 years: Administer as in adults
Metabolized via UDP glucuronidation; P-gp efflux substrate; CYP3A4 inhibitor
UDP-G inducers (eg, rifabutin, phenytoin) and drugs that increase gastric pH (eg, cimetidine) decrease serum levels (avoid concomitant use unless benefit outweighs risk)
Inhibits CYP3A4 and may elevate serum levels of cyclosporine, tacrolimus, sirolimus, rifabutin, midazolam, phenytoin, calcium channel blockers (eg, nifedipine, bepridil), HMG-CoA reductase inhibitors (eg, lovastatin, pravastatin), ergot alkaloids, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine, or vinca alkaloids (eg, vincristine, vinblastine)
Documented hypersensitivity; coadministration with ergot alkaloids; coadministration with CYP3A4 substrates likely to result in serious toxicities (eg, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine)
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
Common adverse effects include nausea, vomiting, diarrhea, rash, hypokalemia, thrombocytopenia, and elevated liver enzyme levels; closely monitor patients with severe diarrhea or vomiting for breakthrough fungal infections; rare adverse events include arrhythmias caused by QTc prolongation, bilirubinemia, or liver function impairment; caution with preexisting cardiac risk factors (eg, history of arrhythmia, hypokalemia, hypomagnesemia); food improves absorption and provides optimal serum concentration; shake well before use; administer with measuring spoon provided in package; avoid if breastfeeding
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.
Adult
Apply sparingly over affected areas bid
Pediatric
Apply as in adults
None reported
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
If sensitivity or irritation develops, discontinue use; for external use only; avoid contact with eyes
Antifungals, polyenes
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.
Adult
0.3-1.5 mg/kg/d IV infused in 5% dextrose over 2-4 h; 10-mg lozenges or 1 mL of a 100-mg/mL sol PO qid
Candiduria: Continuous bladder irrigation at concentrations of 50 mg/L for 3 consecutive days
Pediatric
Administer as in adults; typically better tolerated in neonates than in adults and has improved CSF penetration
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 function, serum electrolytes such as magnesium and potassium, liver function, CBC, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients with neutropenia who are receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock; nephrotoxicity may occur and may be irreversible
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.
Adult
ABLC: 5 mg/kg/d IV, duration of infusion 1-2 h
ABCD: 3-6 mg/kg/d IV, duration of infusion 1-2 h
L-AMB: 1-7 mg/kg/d IV, duration of infusion 1-2 h
Pediatric
Administer as in adults
Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the 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 function, serum electrolytes such as magnesium and potassium, liver function, CBC, and hemoglobin concentrations; resume therapy at the lowest level (eg, 0.25 mg/kg) when therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients with neutropenia who are receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock
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.
Adult
Thrush: 200,000 U lozenge qid, or 500,000 U swish and swallow qid, or 2 500,000 U tabs tid for 14 d
Cutaneous infections: Apply topically tid/qid for 7-14 d
Pediatric
100,000 U (one mL) in each cheek qid for oral thrush in infants
None reported
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
Not for treatment of systemic mycoses; large oral doses may cause gastrointestinal distress; patients often complain of bitter taste
Antimetabolite
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.
Adult
100-150 mg/kg/d PO divided q6h
Pediatric
Administer as in adults
Amphotericin B may increase toxicity of flucytosine; cytosine may inactivate flucytosine
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
Caution in bone marrow suppression; adjust dose in renal impairment
Antifungals, Echinocandins
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.
Adult
70 mg IV over 1 h on day 1; 50 mg IV qd thereafter
Pediatric
Not established; may use if patient refractory to standard therapy; 50 mg/m2/d IV suggested; other sources suggest 2 mg/kg/d IV (dosing based on surface area may be best)
Coadministration with cyclosporine may increase risk of hepatotoxicity; carbamazepine, nelfinavir, efavirenz, or dexamethasone may decrease levels of caspofungin; caspofungin may decrease levels of tacrolimus; rifampin decreases caspofungin levels by 30% (ie, adjust dose to 70 mg/d)
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
Caution in moderate hepatic dysfunction (ie, decrease dose to 35 mg/d); may exacerbate preexisting renal dysfunction or myelosuppression; adverse effects include gastrointestinal upset, skin reactions, rare anaphylaxis, and pulmonary infiltrates
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.
Adult
Candidiasis prophylaxis: 50 mg IV qd infused over 1 h
Esophageal candidiasis: 150 mg IV qd infused over 1 h
Pediatric
4 mg/kg/d IV; neonate dosing may be larger than expected
Increases sirolimus and nifedipine AUC approximately 20%
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
Common adverse effects may include headache, nausea, vomiting, and abdominal pain; other adverse effects include skin rash, delirium, phlebitis, shock, leukopenia, and hyperbilirubinemia; rare cases of elevated hepatic enzyme, BUN, and creatine levels have been reported; transient acute intravascular hemolysis and hemoglobinuria may occur; do not mix or infuse in same IV line with other medications because precipitate forms with other commonly used medications (flush existing IV line with 0.9% NaCl before and after infusion); protect from light following dilution
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).
Adult
Candidemia: 200 mg IV on day 1, decrease dose on day 2 and thereafter to 100 mg/d IV
Esophageal candidiasis: 100 mg IV on day 1, decrease dose on day 2 and thereafter to 50 mg/d IV
Do not exceed infusion rate of 1.1 mg/min
Pediatric
Not established
None reported
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
Common adverse effects include hypokalemia, diarrhea, elevated hepatic enzyme levels, and headache; rare reports of serious hepatotoxicity; infusion-related reactions (eg, rash, urticaria, flushing, pruritus, dyspnea, hypotension) may occur, particularly with rapid infusion; following reconstitution, dilute further with D5W or NS before administration
Antifungal Agents, Allylamine
These are fungicidal agents.
Terbinafine (Daskil, Lamisil)
Inhibits squalene epoxidase, which decreases ergosterol synthesis, causing fungal-cell death.
Use medication until symptoms significantly improve.
Adult
250 mg/d PO; not to exceed 12 wk
Nail infections: Treatment usually requires 3 mo
Pediatric
Weight-based dosing (PO):
12-20 kg: 62.5 mg/d
20-40 kg: 125 mg/d
> 40 kg: 250 mg/d
Treatment duration as in adults
May decrease cyclosporine effects; toxicity of terbinafine may increase with rifampin and cimetidine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue use if chemical irritation develop with topical use; if hepatobiliary dysfunction, neutropenia, Stevens-Johnson syndrome, or changes in ocular lens or retina develop, discontinue use
More on Candidiasis |
| Overview: Candidiasis |
| Differential Diagnoses & Workup: Candidiasis |
 Treatment & Medication: Candidiasis |
| Follow-up: Candidiasis |
| Multimedia: Candidiasis |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. Mar 1 2009;48(5):503-35. [Medline].
Sullivan DJ, Westerneng TJ, Haynes KA, Bennett DE, Coleman DC. Candida dubliniensis sp. nov.: phenotypic and molecular characterization of a novel species associated with oral candidosis in HIV-infected individuals. Microbiology. Jul 1995;141 ( Pt 7):1507-21. [Medline].
Hachem R, Hanna H, Kontoyiannis D, Jiang Y, Raad I. The changing epidemiology of invasive candidiasis: Candida glabrata and Candida krusei as the leading causes of candidemia in hematologic malignancy. Cancer. Jun 2008;112(11):2493-9. [Medline].
Trofa D, Gacser A, Nosanchuk JD. Candida parapsilosis, an emerging fungal pathogen. Clin Microbiol Rev. Oct 2008;21(4):606-25. [Medline].
Wellinghausen N, Moericke A, Bundschuh S, Friedrich W, Schulz AS, Gatz SA. Multifocal osteomyelitis caused by Candida dubliniensis. J Med Microbiol. Mar 2009;58:386-90. [Medline].
van Hal SJ, Stark D, Harkness J, Marriott D. Candida dubliniensis Meningitis as delayed sequela of treated C. dubliniensis Fungemia. CDC. Available at http://www2a.cdc.gov/ncidod/ts/print.asp. Accessed January 29, 2008.
Hirshoren N, Eliashar R, Weinberger JM. Candida epiglottitis: a rare emergent condition--appearance, treatment and pitfalls. Eur J Intern Med. Dec 2008;19(8):e84-5. [Medline].
Yildirim M, Ozaydin I, Sahin I, Yasar M. Acute calculous cholecystitis caused by Candida lusitaniae: an unusual causative organism in a patient without underlying malignancy. Jpn J Infect Dis. Mar 2008;61(2):138-9. [Medline].
Chassot F, Negri MF, Svidzinski AE, Donatti L, Peralta RM, Svidzinski TI, et al. Can intrauterine contraceptive devices be a Candida albicans reservoir?. Contraception. May 2008;77(5):355-9. [Medline].
Loulergue P, Mahe V, Bougnoux ME, Poiree S, Hot A, Lortholary O. Fournier's gangrene due to Candida glabrata. Med Mycol. Mar 2008;46(2):171-3. [Medline].
Stamatakos M, Kontzoglou K, Sargedi C, Tsaknaki S, Safioleas M. Mammary candidiasis. A breast infection difficult to handle. Chirurgia (Bucur). Sep-Oct 2008;103(5):583-6. [Medline].
Mendes V, Castro S, Linhares P, Ribeiro-Silva ML. Tumoriform presentation of cerebral candidiasis in an HIV-infected patient. J Clin Neurosci. Apr 2009;16(4):587-8. [Medline].
Baradkar VP, Mathur M, Kulkarni SD, Kumar S. Thoracic empyema due to Candida albicans. Indian J Pathol Microbiol. Apr-Jun 2008;51(2):286-8. [Medline].
McGee SM, Thompson CA, Granberg CF, Hutcheson JC, Vandersteen DR, Reinberg Y, et al. Acute renal infarction due to fungal vascular invasion in disseminated candidiasis. Urology. Mar 2009;73(3):535-7. [Medline].
Cha JG, Hong HS, Koh YW, Kim HK, Park JM. Candida albicans osteomyelitis of the cervical spine. Skeletal Radiol. Apr 2008;37(4):347-50. [Medline].
Ozdemir N, Celik L, Oguzoglu S, Yildirim L, Bezircioglu H. Cervical vertebral osteomyelitis and epidural abscess caused by Candida albicans in a patient with chronic renal failure. Turk Neurosurg. Apr 2008;18(2):207-10. [Medline].
Guillen Fiel G, Gonzalez-Granado LI, Mosqueda R, Negreira S, Giangaspro E. [Arthritis caused by Candida in an immunocompetent infant with a history of systemic candidiasis in the neonatal period.]. An Pediatr (Barc). Apr 2009;70(4):383-5. [Medline].
Tiraboschi IN, Niveyro C, Mandarano AM, Messer SA, Bogdanowicz E, Kurlat I, et al. Congenital candidiasis: confirmation of mother-neonate transmission using molecular analysis techniques. Med Mycol. Mar 20 2009;1-5. [Medline].
Thompson GR 3rd, Wiederhold NP, Vallor AC, Villareal NC, Lewis JS 2nd, Patterson TF. Development of caspofungin resistance following prolonged therapy for invasive candidiasis secondary to Candida glabrata infection. Antimicrob Agents Chemother. Oct 2008;52(10):3783-5. [Medline].
De Rosa FG, Garazzino S, Pasero D, Di Perri G, Ranieri VM. Invasive candidiasis and candidemia: new guidelines. Minerva Anestesiol. Dec 17 2008;[Medline].
Martinez RC, Franceschini SA, Patta MC, Quintana SM, Candido RC, Ferreira JC, et al. Improved treatment of vulvovaginal candidiasis with fluconazole plus probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Lett Appl Microbiol. Mar 2009;48(3):269-74. [Medline].
Liu CY, Huang LJ, Wang WS, Chen TL, Yen CC, Yang MH, et al. Candidemia in cancer patients: impact of early removal of non-tunneled central venous catheters on outcome. J Infect. Feb 2009;58(2):154-60. [Medline].
Magill SS, Swoboda SM, Shields CE, Colantuoni EA, Fothergill AW, Merz WG, et al. The epidemiology of Candida colonization and invasive candidiasis in a surgical intensive care unit where fluconazole prophylaxis is utilized: follow-up to a randomized clinical trial. Ann Surg. Apr 2009;249(4):657-65. [Medline].
Buergers R, Rosentritt M, Schneider-Brachert W, Behr M, Handel G, Hahnel S. Efficacy of denture disinfection methods in controlling Candida albicans colonization in vitro. Acta Odontol Scand. Jun 2008;66(3):174-80. [Medline].
Sanita PV, Vergani CE, Giampaolo ET, Pavarina AC, Machado AL. Growth of Candida species on complete dentures: effect of microwave disinfection. Mycoses. Mar 2009;52(2):154-60. [Medline].
Anttila VJ, Salonen J, Ylipalosaari P, Koivula I, Riikonen P, Nikoskelainen J. A retrospective nationwide case study on the use of a new antifungal agent: patients treated with caspofungin during 2001-2004 in Finland. Clin Microbiol Infect. Jun 2007;13(6):606-12. [Medline].
Borman AM, Petch R, Linton CJ, Palmer MD, Bridge PD, Johnson EM. Candida nivariensis, an emerging pathogenic fungus with multidrug resistance to antifungal agents. J Clin Microbiol. Mar 2008;46(3):933-8. [Medline].
Brion LP, Uko SE, Goldman DL. Risk of resistance associated with fluconazole prophylaxis: systematic review. J Infect. Jun 2007;54(6):521-9. [Medline].
Charles PE. Multifocal Candida species colonization as a trigger for early antifungal therapy in critically ill patients: what about other risk factors for fungal infection?. Crit Care Med. Mar 2006;34(3):913-4. [Medline].
Cohen and Powderly's: Infectious Diseases. 2nd ed. 2004.
Healy CM, Baker CJ, Zaccaria E, Campbell JR. Impact of fluconazole prophylaxis on incidence and outcome of invasive candidiasis in a neonatal intensive care unit. J Pediatr. Aug 2005;147(2):166-71. [Medline].
Kauffman CA. Candidemia in adults. 2007;Available at uptodate.com.
Kauffman CA. Hepatosplenic candidiasis. 2007;Available at uptodate.com.
Kauffman CA. Overview of Candida infections. 2007;Available at uptodate.com.
Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M, Grossman LB. Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <100 grams birth weight. J Pediatr. 2005;147(2):172-9. [Medline].
Kiss H, Petricevic L, Husslein P. Prospective randomised controlled trial of an infection screening programme to reduce the rate of preterm delivery. BMJ. Aug 14 2004;329(7462):371. [Medline].
Kuse ER, Chetchotisakd P, da Cunha CA, Ruhnke M, Barrios C, Raghunadharao D, et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. May 5 2007;369(9572):1519-27. [Medline].
Li L, Redding S, Dongari-Bagtzoglou A. Candida glabrata: an emerging oral opportunistic pathogen. J Dent Res. Mar 2007;86(3):204-15. [Medline].
Long SS, Stevenson DK. Reducing Candida infections during neonatal intensive care: management choices, infection control, and fluconazole prophylaxis. J Pediatr. Aug 2005;147(2):135-41. [Medline].
Lum LC. Candidal bloodstream infection: will prevention work?. Pediatr Crit Care Med. Mar 2006;7(2):184-5. [Medline].
Makhoul IR, Bental Y, Weisbrod M, Sujov P, Lusky A, Reichman B, et al. Candidal versus bacterial late-onset sepsis in very low birthweight infants in Israel: a national survey. J Hosp Infect. Mar 2007;65(3):237-43. [Medline].
[Best Evidence] Manzoni P, Stolfi I, Pugni L, Decembrino L, Magnani C, Vetrano G, et al. A multicenter, randomized trial of prophylactic fluconazole in preterm neonates. N Engl J Med. Jun 14 2007;356(24):2483-95. [Medline].
Ostrosky-Zeichner L. Prophylaxis for invasive candidiasis in the intensive care unit: is it time?. Crit Care Med. Sep 2005;33(9):2121-2. [Medline].
Ostrosky-Zeichner L, Pappas PG. Invasive candidiasis in the intensive care unit. Crit Care Med. Mar 2006;34(3):857-63. [Medline].
Pappas PG. Invasive candidiasis. Infect Dis Clin North Am. Sep 2006;20(3):485-506. [Medline].
Parker ER, Guitart J. Candidal Intertrigo. 2007;Available at uptodate.com.
Patel DA, Gillespie B, Sobel JD, Leaman D, Nyirjesy P, Weitz MV, et al. Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: results of a prospective cohort study. Am J Obstet Gynecol. Mar 2004;190(3):644-53. [Medline].
Phillips AJ. Treatment of non-albicans Candida vaginitis with amphotericin B vaginal suppositories. Am J Obstet Gynecol. Jun 2005;192(6):2009-12; discussion 2012-3. [Medline].
Piarroux R, Grenouillet F, Balvay P, Tran V, Blasco G, Millon L, et al. Assessment of preemptive treatment to prevent severe candidiasis in critically ill surgical patients. Crit Care Med. Dec 2004;32(12):2443-9. [Medline].
Mandell, Bennet and Dolin. Principles and Practice of Infectious Diseases. 6th ed. 2005.
[Best Evidence] Reboli AC, Rotstein C, Pappas PG, Chapman SW, Kett DH, Kumar D, et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. Jun 14 2007;356(24):2472-82. [Medline].
Singhi SC, Reddy TC, Chakrabarti A. Candidemia in a pediatric intensive care unit. Pediatr Crit Care Med. Jul 2004;5(4):369-74. [Medline].
Smith PB, Steinbach WJ, Benjamin DK Jr. Neonatal candidiasis. Infect Dis Clin North Am. Sep 2005;19(3):603-15. [Medline].
Sobel JD, Wiesenfeld HC, Martens M, Danna P, Hooton TM, Rompalo A, et al. Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. N Engl J Med. Aug 26 2004;351(9):876-83. [Medline].
Spinillo A, Zara F, Gardella B, Preti E, Mainini R, Maserati R. The effect of vaginal candidiasis on the shedding of human immunodeficiency virus in cervicovaginal secretions. Am J Obstet Gynecol. Mar 2005;192(3):774-9. [Medline].
Sun RL, Jones DB, Wilhelmus KR. Clinical characteristics and outcome of Candida keratitis. Am J Ophthalmol. Jun 2007;143(6):1043-1045. [Medline].
Wells CL, Johnson MA, Henry-Stanley MJ, Bendel CM. Candida glabrata colonizes but does not often disseminate from the mouse caecum. J Med Microbiol. May 2007;56(Pt 5):688-93. [Medline].
Wertz KK, Pretzlaff RK. Caspofungin in a pediatric patient with persistent candidemia. Pediatr Crit Care Med. Mar 2004;5(2):181-3. [Medline].
Zaas AK, Dodds Ashley ES, Alexander BD, Johnson MD, Perfect JR. Caspofungin for invasive candidiasis at a tertiary care medical center. Am J Med. Nov 2006;119(11):993.e1-6. [Medline].
Zhang AY, Camp WL, Elewski BE. Advances in topical and systemic antifungals. Dermatol Clin. Apr 2007;25(2):165-83, vi. [Medline].
Further Reading
Clinical guidelines
Guidelines for treatment of candidiasis. Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. Mar 1 2009;48(5):503-35.
Keywords
candidiasis, Candida albicans, C albicans, Candida tropicalis, C tropicalis, Candida parapsilosis, C parapsilosis, Candida guilliermondi, C guilliermondi, Candida lusitaniae, C lusitaniae, Candida krusei, C krusei, Torulopsis glabrata, Tglabrata, mycotic infection, vaginitis, vulvar rash, oral thrush, conjunctivitis, endophthalmitis, diaper rash, infections of nail, infections of rectum, infections of skin folds, systemic candidiasis, oral candidiasis, gastrointestinal candidiasis, red macerated intertriginous areas, vulvovaginitis, candidal infection, nosocomial bloodstream infection, candidemia, fungemia, vulvovaginal candidiasis, candidal esophagitis
