eMedicine Specialties > Infectious Diseases > Fungal Infections
Candidiasis: Treatment & Medication
Updated: Jan 11, 2010
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Treatment
Medical Care
The treatments used to manage Candida infections vary substantially and are based on the anatomic location of the infection, the patients' underlying disease and immune status, the patients' risk factors for infection, the specific species of Candida responsible for infection, and, in some cases, the susceptibility of the Candida species to specific antifungal drugs.
There have been significant changes in the management of candidiasis in the last few years, particularly related to the appropriate use of echinocandins and expanded-spectrum azoles for candidemia, other forms of invasive candidiasis, and mucosal candidiasis. Newer updated guidelines were published in March 2009 by the Infectious Disease Society of America (IDSA),21 replacing a previous version from 2004.22 These latest recommendations include the echinocandins caspofungin, micafungin, and anidulafungin, along with voriconazole and posaconazole, as well as lipid formulations of amphotericin B in various situations. Fluconazole is still considered a first-line agent in nonneutropenic patients with candidemia or suspected invasive candidiasis. The therapeutic options available for the management of invasive candidiasis and candidemia have continued to increase with the addition of newer echinocandins23,24 and triazoles.
- Cutaneous candidiasis: Most localized cutaneous candidiasis infections may be treated with any number of topical antifungal agents (eg, clotrimazole, econazole, ciclopirox, miconazole, ketoconazole, nystatin). If the infection is a paronychia, the most important aspect of therapy is drainage of the abscess, followed by oral antifungal therapy with either fluconazole or itraconazole. In cases of extensive cutaneous infections, infections in immunocompromised patients, folliculitis, or onychomycosis, systemic antifungal therapy is recommended. For Candida onychomycosis, oral itraconazole (Sporanox) appears to be most efficacious. Two treatment regimens are available: the daily dose of itraconazole taken for 3-6 months or the pulsed-dose regimen that requires a slightly higher daily dose for 7 days, followed by 3 weeks of no drug administration. The cycle is repeated every month for 3-6 months.
- Gastrointestinal candidiasis
- Oropharyngeal candidiasis
- Oropharyngeal candidiasis OPC can be treated with either topical antifungal agents (eg, nystatin, clotrimazole, amphotericin B oral suspension) or systemic oral azoles (fluconazole, itraconazole, or posaconazole).
- Infections in HIV-positive patients tend to respond more slowly and, in approximately 60% of patients, recur within 6 months of the initial episode. Approximately 3-5% of patients with advanced HIV infection (CD4 cell counts <50/µL) may develop refractory OPC. In these situations, in addition to attempting correction of the immune dysfunction with HAART, higher doses of fluconazole (up to 800 mg/d) or itraconazole (up to 600 mg/d) can be attempted. Posaconazole suspension at 400 mg orally twice per day has also yielded excellent results in such patients. Additionally, caspofungin 50 mg/d IV and anidulafungin 100 mg/d IV have also yielded excellent efficacy in such patents. Amphotericin B is rarely necessary to treat such cases, but, when used, low doses of amphotericin B can be used (0.3-0.7 mg/kg) and have been shown to be effective.
- Candida esophagitis requires systemic therapy with fluconazole for 14-21 days. Parenteral therapy with fluconazole may be required initially if the patient is unable to take oral medications. Daily suppressive antifungal therapy with fluconazole 100-200 mg/d is effective for preventing recurrent episodes, but it should be used only if the recurrences become frequent or are associated with malnutrition due to poor oral intake and wasting syndrome. Recommended alternatives for fluconazole-refractory disease include itraconazole, voriconazole, caspofungin, micafungin, anidulafungin, and amphotericin B.
- Oropharyngeal candidiasis
- Genitourinary tract candidiasis
- Vulvovaginal candidiasis (VVC) can be managed with either topical antifungal agents or a single dose of oral fluconazole.25 A single dose of oral fluconazole (150 mg) in acute episodes of VVC has been shown to yield clinical and microbiological efficacy as good as or better than topical antifungal agents. A small percentage (<5%) of women experience chronic recurrent VVC infections, which often require long-term or prophylactic oral azole therapy for control. In such patients, the recommended regimen includes fluconazole 150 mg every other day for 3 doses, followed by weekly fluconazole 150-200 mg for 6 months.9 This regimen prevents further recurrence in more than 80% of women.
- For asymptomatic candiduria, therapy generally depends on the presence or absence of an indwelling Foley catheter. Candiduria frequently resolves by simply changing the Foley catheter (20-25% of patients). Thus, most experts agree that asymptomatic candiduria associated with a Foley catheter does not require treatment in most cases. However, eradicating candiduria prior to any form of instrumentation or urological manipulation is prudent.
- Candida cystitis in noncatheterized patients should be treated with fluconazole at 200 mg/d orally for at least 10-14 days.
- For Candida cystitis in catheterized patients, the first step is always to remove the nidus of infection. Thus, the Foley catheter should be removed or replaced prior to initiating antifungal therapy. If the candiduria persists after the catheter change, then patients can be treated with 200 mg/d of fluconazole orally for 14 days. Alternative therapy includes amphotericin B bladder irrigation. However, its use for the treatment of funguria is significantly limited, primarily because of the required maintenance of a urinary catheter; lack of adequate studies to define the dose, duration, and method of administration; restriction of its use to uncomplicated lower urinary tract infections; and the availability of more convenient treatment options (eg, oral fluconazole therapy). The use of amphotericin B bladder irrigation is rarely needed. Administering intravenous amphotericin B to treat candiduria is rarely necessary.
- Renal candidiasis: Regardless of whether the infection involves hematogenous dissemination to the kidney or ascending infection (pyelonephritis), systemic antifungal therapy is required. The most recent comparative studies indicate that fluconazole at 400 mg/d intravenously or orally for a minimum of 2 weeks is as effective as amphotericin B without the toxicities normally associated with amphotericin B. For amphotericin B, the daily dose is 0.5-0.7 mg/kg intravenously for a total dose of 1-2 g administered over a 4- to 6-week period.
- Candidemia: This requires treatment in all patient populations. Current recommendations depend on the presence or absence of neutropenia.21
- In patients without neutropenia, fluconazole is the drug of choice in most cases of candidemia and disseminated candidiasis. Studies conducted by the MSG have demonstrated that fluconazole at a dose of 400 mg/d is as efficacious as amphotericin B. In addition, fluconazole has several advantages, including lower nephrotoxicity rates (<2%) and ease of use because of the high degree of bioavailability and the long half-life of the drug.26 Thus, once the gastrointestinal tract is functional, the parenteral antifungal may be switched to the oral formulation with the same efficacy. Alternative options listed below need to be considered depending on history of previous exposure to antifungals, the probability of fluconazole resistance according to the species of Candida recovered, the presence of comorbid conditions, and the clinical status of the patient.27
- An echinocandin is recommended for candidemia in most patients with neutropenia. Fluconazole is an alternative in patients who are less critically ill and who have no recent azole exposure. Voriconazole can be used when additional mold coverage is desired.
- The standard recommended dose for fluconazole is 800 mg as the loading dose, followed by fluconazole at a dose of 400 mg/d for at least 2 weeks of therapy after a demonstrated negative blood culture result or clinical signs of improvement. This treatment regimen can be used for infections due to C albicans, C tropicalis, C parapsilosis, C kefyr, C dubliniensis, C lusitaniae, and C guilliermondi.
- A critical component in the management of candidemia and disseminated candidiasis is the removal of the focus of infection, such as intravenous and Foley catheters.
- Available echinocandins for candidemia include the following:
- Caspofungin (Cancidas) can be initiated as a 70-mg loading dose, followed by 50 mg/d intravenously to complete a minimum of 2 weeks of antifungals after improvement and after blood cultures have cleared. Caspofungin is a broad-spectrum semisynthetic echinocandin. It is an effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non-albicans Candida species such as C glabrata.
- Anidulafungin can be initiated as a 200-mg loading dose, followed by 100 mg intravenously to complete a minimum of 2 weeks of antifungals after improvement and after blood cultures have cleared. Anidulafungin is a broad-spectrum echinocandin. It is an effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non-albicans Candida species such as C glabrata.28
- Micafungin can be administered at 100 mg/d intravenously to complete a minimum of 2 weeks of antifungals after improvement and after blood cultures have cleared. Micafungin is a broad-spectrum echinocandin. It has been shown to be an effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non-albicans Candida species such as C glabrata.29
- Additional options for candidemia include the following:
- Voriconazole can be initiated at 6 mg/kg intravenously or orally twice per day, followed by 3 mg/kg orally twice per day or 200 mg orally twice per day. Based on the findings from a global multicenter clinical trial, voriconazole has also been approved for use in candidemia in patients who are not neutropenic.30
- Amphotericin B deoxycholate can be administered at 0.7 mg/kg/d intravenously for a total dose of 1-2 g over a 4- to 6-week period.
- Liposomal preparations of amphotericin B have comparable efficacy to conventional amphotericin B, but renal toxicity is considerably less common with the former.
- Chronic mucocutaneous candidiasis: This condition is generally treated with oral azoles, such as fluconazole at a dose of 100-400 mg/d or itraconazole at a dose of 200-600 mg/d until the patient improves. The initial therapy for acute infection is always followed by maintenance therapy with the same azole for life.
- Hepatosplenic candidiasis: Induction therapy is initially started with amphotericin B deoxycholate for at least 2 weeks, followed by consolidation therapy with fluconazole at a dose of 400 mg/d for an additional 4-12 weeks depending on the response.
- Respiratory tract candidiasis: If the diagnosis is established based on biopsy findings, then the infection is treated as disseminated candidiasis.
- Empirical treatment options for suspected invasive candidiasis include the following:
- Empirical antifungal therapy should be considered for critically ill patients with risk factors for invasive candidiasis and no other cause of fever, and it should be based on clinical assessment of risk factors, serologic markers for invasive candidiasis, and/or culture data from nonsterile sites. (Its benefits have not been clearly determined.)31
- This continues to be a problematic decision since criteria for starting empirical antifungal therapy remain poorly defined. Empirical therapy in persistently febrile and neutropenic patients should cover infections caused by yeasts and molds.
- The choice of drugs in nonneutropenic patients is similar to that for proven candidiasis. Recommended agents include fluconazole or an echinocandin.
- In neutropenic patients, a lipid formulation of amphotericin B, caspofungin, or voriconazole is recommended. Azoles should not be used for empirical therapy in individuals who have received an azole for prophylaxis.
- Disseminated candidiasis with end organ infection: Disseminated candidiasis with end organ involvement requires an individualized approach. Thus, the manifestation of invasive candidiasis involving localized structures, such as in Candida osteomyelitis, arthritis, endocarditis, pericarditis, and meningitis, requires prolonged antifungal therapy for at least 4-6 weeks. The optimum dosage and duration of therapy for various types of deep candidal infection have not been definitively determined.
- The standard recommended dose for most Candida infections is fluconazole at 800 mg as the loading dose, followed by fluconazole at a dose of 400 mg/d either intravenously or orally for at least 2 weeks of therapy after a demonstrated negative blood culture result or clinical signs of improvement.
- The echinocandins have become first-line therapy for this type of infection in many situations because of their efficacy and low incidence of adverse events and drug interactions.
- Caspofungin (Cancidas)32 can be initiated as a 70-mg loading dose, followed by 50 mg/d intravenously to complete a minimum of 2 weeks of antifungals after improvement and after blood cultures have cleared. Caspofungin is a broad-spectrum semisynthetic echinocandin. It is an effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non-albicans Candida species such as C glabrata.
- Anidulafungin can be initiated as a 200-mg loading dose, followed by 100 mg intravenously to complete a minimum of 2 weeks of antifungals after improvement and after blood cultures have cleared. Anidulafungin is a broad-spectrum echinocandin. It is an effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non-albicans Candida species such as C glabrata.28
- Micafungin can be administered at 100 mg/d intravenously to complete a minimum of 2 weeks of antifungals after improvement and after blood cultures have cleared. Micafungin is a broad-spectrum echinocandin. It has been shown to be an effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non-albicans Candida species such as C glabrata.29
- Voriconazole can be initiated at 6 mg/kg intravenously or orally twice per day, followed by 3 mg/kg orally twice per day or 200 mg orally twice per day. Based on the findings from a global multicenter clinical trial, voriconazole has also been approved for use in candidemia in patients who are not neutropenic.30
- Amphotericin B deoxycholate has been an alternative to fluconazole for many years. However, with the advent of the newer azoles and the echinocandins, its role as a primary or secondary option needs to be reconsidered. The dose for amphotericin B deoxycholate is 0.5-0.7 mg/kg/d intravenously to achieve a minimum of 1- to 2-g total dose. For the treatment of invasive candidiasis caused by less-susceptible species, such as C glabrata and C krusei, higher doses (up to 1 mg/kg/d) should be considered.
- Liposomal preparations of amphotericin B are recommended at doses between 3 and 5 mg/kg/d when used for invasive candidiasis.
- Special situations involving antifungal resistance: Several of the Candida species require special mention because of their known intrinsic resistance to antifungals.
- Because C glabrata is known to be resistant to fluconazole in 15-25% of cases and has decreased susceptibility to most antifungals, C glabrata infections require a change in conventional antifungal therapy. The drugs of choice for such infections are the echinocandins: caspofungin 70 mg intravenously as a loading dose, followed by 50 mg/d; anidulafungin 200-mg loading dose, followed by 100 mg/d; or micafungin 100 mg/day intravenously. An alternative is voriconazole at 6 mg/kg administered twice on the first day, followed by 3 mg/kg twice per day or 200 mg twice per day orally; other options include amphotericin B deoxycholate (1 mg/kg/d), or lipid preparations of amphotericin B at 3-5 mg/kg/d.
- If in vitro susceptibility assays are available, it may be worthwhile to establish the in vitro susceptibility of the C glabrata strain to fluconazole. If the MIC is less than 8 μg/mL, then fluconazole can be used at 400 mg/d intravenously or orally.
- C krusei infections necessitate the use of an agent other than fluconazole because this organism is intrinsically resistant to fluconazole and has a decreased susceptibility to itraconazole, ketoconazole, and amphotericin B. Thus, the preferred regimen includes echinocandins (caspofungin, anidulafungin, or micafungin) voriconazole, or amphotericin B at 1 mg/kg/d. Infections due to C lusitaniae or C guilliermondi necessitate the use of fluconazole, voriconazole, or the echinocandins because these isolates are frequently intrinsically resistant to amphotericin B or develop resistance to amphotericin B while the patient is on therapy.
- Alternative antifungal regimens
- Alternative regimens may be considered in patients who are intolerant to the treatment regimens or when the infection is refractory to the antifungal regimen. The combination of amphotericin B and flucytosine has been recommended in several special situations. For instance, this combination has been used in immunocompromised patients with endophthalmitis, meningitis, or osteomyelitis. Flucytosine appears to interact synergistically with amphotericin B in animal models.
- The role of other combinations of antifungals to treat complicated Candida infections needs to be evaluated. A human recombinant monoclonal antibody against heat shock protein 90 was recently reported to significantly improve outcomes in patients treated with lipid-associated amphotericin B for confirmed invasive candidiasis.33 However, larger randomized trials need to be performed before this drug can be used clinically.
Surgical Care
- Major organ infections associated with candidal abscess formation may require surgical drainage procedures along with the appropriate antifungal therapy.
- Prosthetic joint infection with Candida species requires the removal of the prosthesis.
- Surgical debridement is generally necessary for sternal infections and frequently for vertebral osteomyelitis.
- Splenic abscesses occasionally require splenectomy.
- Valve replacement surgery is always indicated to treat endocarditis.
- In addition to medical management, vitrectomy is a therapeutic option in fungal endophthalmitis.34
Consultations
In some forms of candidiasis, involving physicians of different specialties for some of the specific infections may be necessary. Some examples of these situations include endocarditis, endophthalmitis, peritonitis, osteomyelitis, and other forms of invasive candidiasis that may require surgical drainage and debridement.
- Ophthalmologist
- General surgeon
- Cardiothoracic surgeon
- Gastroenterologist
- Infectious disease specialist
- Orthopedic surgeon
Medication
Successful therapy for serious systemic Candida infections requires initiation of antifungal therapy as early as possible, as soon as adequate culture results are obtained.
Different classes of antifungals are now available to manage any type of candidal infection. Azoles, fluconazole in particular,26 have become the mainstay of therapy over the past few years. These include topical and systemic agents. Posaconazole is the most recent addition to this group of antifungals. Polyenes include amphotericin B, liposomal amphotericin B formulations, and topical nystatin. Allylamines include terbinafine, which is formulated in a topical preparation and an oral tablet. The newest group of antifungals is echinocandins, including caspofungin, micafungin, and anidulafungin. These drugs have shown excellent clinical efficacy, a low incidence of adverse events, a good safety profile, and ease of use.35,36
Azole Antifungals
These agents are synthetic compounds that include 2 groups, imidazoles and triazoles. Triazoles have 3 atoms of nitrogen in the azole ring. Imidazoles have only two. The primary mechanism of action is inhibition of lanosterol 14-alpha-demethylase, an enzyme required for the synthesis of ergosterol, the main component of fungal cell membranes. Imidazole agents include miconazole, ketoconazole, and clotrimazole. Triazole agents, which are now the most commonly used azoles, include fluconazole, itraconazole, econazole, terconazole, butoconazole, and tioconazole. Newer triazoles (ie, voriconazole, posaconazole, ravuconazole) are active against fluconazole-resistant strains of Candida. Voriconazole and posaconazole have shown high efficacy against candidiasis in recent clinical trials.37,30,38
Topical agents are frequently used as front-line agents to manage localized or superficial forms of candidiasis such as cutaneous candidiasis, oropharyngeal candidiasis (OPC), and vulvovaginal candidiasis (VVC). These preparations are available as a cream for topical use, as troches for OPC, and as a vaginal suppositories or tablets for vaginitis.
Fluconazole (Diflucan)
Triazole with less effect on human sterol metabolism. Does not decrease cortisol and testosterone levels, as occurs with ketoconazole. Has fewer adverse effects and better tissue distribution than older systemic imidazoles. Available PO/IV and has demonstrated efficacy in topical and invasive forms of candidiasis. Available in 50-, 100-, 150-, and 200-mg tabs.
Daily dose varies with indication.
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 transplantation
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 may decrease mortality in transplant recipients
Pediatric
<2 weeks: Administer q72h IV
>2 weeks: 3 mg/kg/d PO/IV for superficial infections and 6-12 mg/kg/d for systemic infections
Inhibits cytochrome P450 hepatic enzymes to cause increased levels of atovaquone, AZT, benzodiazepines, clarithromycin, cyclosporine, oral hypoglycemics, phenytoin, rifabutin, saquinavir, tacrolimus, theophylline, terfenadine, and warfarin; levels may increase with hydrochlorothiazide; levels may decrease with long-term coadministration of rifampin, rifabutin, and phenytoin
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
Nausea, vomiting, diarrhea, and allergic reactions are most common adverse effects; adjust dose for renal insufficiency; monitor closely if rash develops and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) with underlying medical conditions (eg, AIDS, malignancy) and while taking multiple concomitant medications; not recommended during breastfeeding
Itraconazole (Sporanox)
Has fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P450-dependent synthesis of ergosterol, a vital component of fungal cell membranes. Effective against broad range of fungi, including Candida species, and is indicated for treatment of cutaneous, oral, esophageal, and disseminated candidiasis.
Available IV, 100-mg caps, and oral solution at 10 mg/mL.
Caps 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 caps can be used in onychomycosis and dermatophyte infections.
Adult
Cutaneous candidiasis and onychomycosis: 200 mg PO/IV bid for 7 d/mo for 3-6 mo
OPC and esophageal candidiasis: 200 mg/d PO/IV for 7-14 d
Candidemia and invasive candidiasis: 200 mg PO/IV tid for 3 d, followed by 200 mg PO/IV bid for 14-21 d
Pediatric
Cutaneous candidiasis: 3-5 mg/kg/d PO/IV for 30 d
Antacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin or simvastatin); inhibits cytochrome P450 hepatic enzymes to cause increased levels of atovaquone, AZT, benzodiazepines, clarithromycin, cyclosporine, digoxin, oral hypoglycemics, midazolam phenytoin, rifabutin, saquinavir, tacrolimus, theophylline, triazolam, and warfarin
Levels may decrease with long-term coadministration of rifampin, rifabutin, phenytoin, phenobarbital, carbamazepine, and isoniazid; increases levels of indinavir, saquinavir, and ritonavir; indinavir, ritonavir, and fixed-dose combination of lopinavir/ritonavir increase levels
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 insufficiencies; nausea, vomiting, diarrhea, and abdominal discomfort may occur; high doses may produce hypertension, hypokalemia, or edema; may have negative inotropic effect; exacerbations of congestive heart failure reported, especially with IV administration
Voriconazole (Vfend)
Available as tablet, suspension and parenteral preparations. Effective as fluconazole against esophageal candidiasis, and as effective as amphotericin B deoxycholate in treatment of candidemia and invasive candidiasis. In Europe, it has been approved for "treatment of fluconazole-resistant serious invasive Candida infections (including C krusei)." Additionally, associated with fewer breakthrough fungal infections when used as empiric therapy in febrile neutropenic patients. FDA approved for esophageal candidiasis and candidemia.
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; switch to 200 mg PO q12h when able to tolerate; may increase to 300 mg PO q12h if inadequate response
If <40 kg: Average maintenance dose is 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) and others may mandate more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG-CoA inhibitors, benzodiazepines, calcium channel blockers)
Documented hypersensitivity; CrCl <50 mL/min (decreased excretion of IV vehicle) if administering IV; coadministration with rifampin, rifabutin, carbamazepine, barbiturates, sirolimus, pimozide, quinidine, cisapride, or ergot alkaloids
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
Decrease maintenance dose in 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 disorders; rare cases of severe hepatotoxicity reported; administer PO dose 1 h ac or pc; in renal insufficiency oral dose does not have to be adjusted (however, because of renal clearance of cyclodextrin carrier in parenteral formulation, in patients with creatinine clearance of <50 mL/min drug should be switched from IV to oral formulation)
Posaconazole (Noxafil)
Novel triazole antifungal agent. Blocks ergosterol synthesis of cell membrane by inhibiting enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. Action results in cell membrane disruption. Available as oral susp (200 mg/5 mL). Approved for treatment of OPC, including OPC refractory to itraconazole and/or fluconazole and for prophylaxis of infections due to Candida and Aspergillus in patients who are at high risk, such as those undergoing stem cell transplants with graft versus host disease or with prolonged neutropenia due to a hematologic malignancy or its treatment.
Adult
Available only in suspension at 100 mg (5 mL); recommended dose is from 100 mg PO qd for OPC; 400 mg PO bid for antifungal refractory OPC/EC; drug should be taken with food or a 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 (withdrawn from US market), astemizole (withdrawn from US market), 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
Glucan synthesis inhibitors (echinocandins)
These agents inhibit the formation of fungal cell wall. The antifungal class has expanded with the approvals of caspofungin, micafungin, and anidulafungin. Indications are evolving but have been approved for complicated forms of invasive candidiasis, candidemia, disease refractory to other systemic antifungals, and intolerance to amphotericin B. They are broad spectrum and fungicidal against most Candida species, except C parapsilosis and C guilliermondii.
Caspofungin (Cancidas)
FDA approved to treat candidemia, invasive candidiasis, and esophageal candidiasis. Initially approved to treat refractory invasive aspergillosis. Also approved as empiric therapy for presumed fungal infections in febrile neutropenic patients. First of a new class of antifungal drugs (glucan synthesis inhibitors). Inhibits synthesis of (1,3) β -D-glucan, an essential component of fungal cell wall. This component is not found in mammalian cell walls.
Adult
70 mg IV over 1 h on d 1; 50 mg IV qd thereafter
Pediatric
Not established
Coadministration with cyclosporine may increase risk of hepatotoxicity; coadministration with phenytoin, carbamazepine, nelfinavir, efavirenz, or dexamethasone decrease levels of caspofungin by 30%; may also decrease levels of tacrolimus by approximately 25%
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 (decrease dose); may exacerbate preexisting renal dysfunction or myelosuppression; common adverse events include fevers, chills, headaches phlebitis, nausea, vomiting, diarrhea, rash, and occasionally histamine-induced reactions (rash, urticaria, flushing, pruritus, dyspnea, hypotension); may also produce elevations in transaminases, alkaline phosphatase, bilirubin and serum creatinine, hypokalemia, anemia, thrombocytopenia, and neutropenia
Micafungin (Mycamine)
A member of a new class of antifungal agents, echinocandins, that inhibit cell wall synthesis. Echinocandins inhibit the synthesis of (1,3)-β -D-glucan, an essential component of the fungal cell wall, not present in mammalian cells. Indications include prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation, treatment of esophageal candidiasis, candidemia, and invasive candidiasis.
Adult
Candidiasis prophylaxis stem cell transplant recipient: 50 mg IV qd infused over 1 h; esophageal candidiasis 150 mg IV qd infused over 1 h, and 100 mg qd IV for candidemia and candidiasis
Pediatric
Not established
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 include headache, nausea, vomiting, and abdominal pain; other adverse effects include rash, delirium, phlebitis, leukopenia, and hyperbilirubinemia; elevated transaminases, alkaline phosphatase, bilirubin, and serum creatine; transient acute intravascular hemolysis and hemoglobinuria may occur; occasionally causes histamine-induced reactions; not for mixing or infusing 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)
One of the newer antifungal agents belonging to the echinocandin class. Also inhibits synthesis of (1,3)-β -D-glucan, an essential component of fungal cell walls. Indicated for treatment of esophageal candidiasis, candidemia, and other forms of candidal infections (eg, intra-abdominal abscesses, peritonitis).
Adult
Candidemia or other candidal infections: 200 mg IV on day 1, followed by 100 mg/d IV
Esophageal candidiasis: 100 mg IV on day 1, followed by 50 mg/d IV thereafter
Not to 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 diarrhea, nausea, vomiting, headaches, elevation in transaminases, alkaline phosphatases and hypokalemia; rare 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
Polyenes
These are broad-spectrum fungicidal agents. Mechanism of action is by insertion into fungal cytoplasmic membrane, causing increases in permeability. Membrane channel activity is increased at lower doses, and pores are formed at higher concentrations.
Amphotericin B (Fungizone, Amphocin)
One of the oldest antifungals, in use for more than 40 y, and the criterion standard of antifungal therapy.
In recent years, lipid formulations have been developed. Total dose must be adjusted depending on type of candidal infection being treated. Most patients receive 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 solution PO qid
Candiduria: Continuous bladder irrigation at concentrations of 50 mg/L for 3 consecutive days
Pediatric
Administer as in adults
Concomitant administration of nephrotoxic antibiotics, cyclosporine, other nephrotoxic immunosuppressants, or parenteral pentamidine may lead to an increased risk of nephrotoxicity; may enhance effects of neuromuscular-blocking drugs; may increase toxicity of digitalis glycosides
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Infusion-related toxicity includes acute reactions occurring approximately 30-45 min after beginning infusion; typically, patients have chills, fever, and tachypnea; premedication with acetaminophen or addition of hydrocortisone (25-50 mg) to infusion can diminish reactions; meperidine can shorten rigor; nephrotoxicity (approximately 30-40%); monitor patients receiving any parenteral form of amphotericin B for changes in renal function (BUN, serum creatinine), liver function, and serum electrolytes (eg, serum potassium, magnesium); nephrotoxicity may be decreased by administering 0.5-1 L of 0.9% NS 1-2 h prior to each infusion; normocytic normochromic anemia may develop, usually after 7-10 d of therapy; monitor CBC count with differential 3 times/wk
Amphotericin B, lipid formulations (Amphotec, Abelcet, AmBisome)
Novel lipid formulations of amphotericin B that deliver higher concentrations of drug with a theoretical increase in therapeutic potential and decreased nephrotoxicity.
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 intolerant of conventional amphotericin B or with fungal infections refractory to conventional amphotericin B. L-AMB is approved for aspergillosis, candidiasis, cryptococcosis, and neutropenic patients with 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 potential for renal toxicity, bronchospasm, and hypotension; corticosteroids, digoxin, and thiazides may potentiate hypokalemia; risk of renal toxicity 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
Nephrotoxicity can occur with amphotericin B (approximately 30-50%), ABLC (approximately 25%), ABCD (approximately 20%), or L-AMB (approximately 20%); monitor BUN, serum creatinine, potassium, and magnesium levels daily; infusion-related toxicity can occur with amphotericin B (>50%), ABLC (approximately 30-50%), ABCD (>50%), and L-AMB (approximately 15-30%); manifestations include fever, chills, rigors, nausea, vomiting, hypertension, tachycardia, and hypoxia; elevations in hepatic transaminases, alkaline phosphatases, and serum bilirubin may occur
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. Membrane channel activity is increased at lower doses, and pores are formed at higher concentrations.
Adult
Vaginal candidiasis: 100,000 U vaginal tab; dissolve 1 tab hs for 14 d
OPC: 200,000 U pastille; dissolve 1-2 pastilles qid for 7-14 d; 100,000 U susp; 5 mL swish and swallow qid for 7-14 d
Pediatric
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
Do not use to treat systemic mycoses; adverse GI effects include nausea, vomiting, and diarrhea
Antimetabolite
Flucytosine is an antimetabolite originally developed for the treatment of leukemia.
Flucytosine (Ancobon)
It is deaminated to 5-fluorouracil in the fungal cell by an enzyme not present in mammalian cells, and inhibits RNA and protein synthesis. Active against Candida and Cryptococcus species and generally used in combination with amphotericin B. It has been used in studies in invasive candidiasis. Avoid use as single agent because of ability to quickly develop resistance in vivo.
Adult
100-150 mg/kg/d PO divided q6h
Pediatric
Administer as in adults
Amphotericin B may increase toxicity; 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
Commonly administered in combination with amphotericin B; overall toxicity approximately 30%; adjust dose to produce plasma concentration of 25-50 mcg/mL; myelosuppression associated with blood concentration >100 mcg/mL; adjust dose in renal impairment; CBC count with differential monitored 3 times/wk; occasional hepatotoxicity reported
Topical azoles
These agents are used extensively to treat common mucocutaneous uncomplicated forms of candidiasis.
Clotrimazole (Mycelex, Femizole-7)
Broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells.
Adult
OPC: 10-mg troche to be dissolved in mouth 5 times/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 hs
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
Butoconazole (Femstat-3, Gynazole-1)
Broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells.
Use 2% vaginal cream. Available OTC.
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; external use only; avoid contact with eyes
Miconazole (Monistat, Micatin)
Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased, causing nutrients to leak out, resulting in fungal cell death. Lotion preferred in intertriginous areas. If cream is used, apply sparingly to avoid maceration effects.
Adult
Vaginal candidiasis: Insert a single 200-mg suppository intravaginally hs for 3 d; alternatively, insert 1 applicatorful of 2% vaginal cream intravaginally hs for 7 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; external use only; avoid contact with eyes
Tioconazole (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; external use only; avoid contact with eyes
Terconazole (Terazol-7, Terazol-3)
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 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
Allylamines
These agents cause a deficiency of ergosterol within the fungal cell wall, causing fungal cell death.
Terbinafine (Daskil, Lamisil)
For treatment of paronychia; allylamine antifungal, which inhibits squalene epoxidase and decreases ergosterol synthesis, causing fungal-cell death.
Use medication until symptoms significantly improve.
Duration of treatment should be >1 wk but not >4 wk. May not be as effective for candidal infections as azole antifungals.
Adult
Paronychia: 250 mg PO qd for 12 wk
Pulse dosing: 500 mg PO qd for first wk of month for 2 mo (fingernails) or 4 mo (toenails)
Pediatric
Weight-based dosing (PO):
<12 kg: Not established
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
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References
Pappas PG, Rex JH, Lee J, et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis. Sep 1 2003;37(5):634-43. [Medline].
Yang YL. Virulence factors of Candida species. J Microbiol Immunol Infect. Dec 2003;36(4):223-8. [Medline].
Pappas PG. Invasive candidiasis. Infect Dis Clin North Am. Sep 2006;20(3):485-506. [Medline].
de Repentigny L, Lewandowski D, Jolicoeur P. Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus infection. Clin Microbiol Rev. Oct 2004;17(4):729-59, table of contents. [Medline].
Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. Jan 2007;20(1):133-63. [Medline].
Morgan J. Global trends in candidemia: review of reports from 1995-2005. Curr Infect Dis Rep. Nov 2005;7(6):429-39. [Medline].
Colombo AL, Nucci M, Park BJ, et al. Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers. J Clin Microbiol. Aug 2006;44(8):2816-23. [Medline].
Maródi L, Johnston RB Jr. Invasive Candida species disease in infants and children: occurrence, risk factors, management, and innate host defense mechanisms. Curr Opin Pediatr. Dec 2007;19(6):693-7. [Medline].
Sobel JD. Vulvovaginal candidosis. Lancet. Jun 9 2007;369(9577):1961-71. [Medline].
Malani AN, Kauffman CA. Candida urinary tract infections: treatment options. Expert Rev Anti Infect Ther. Apr 2007;5(2):277-84. [Medline].
Guery BP, Arendrup MC, Auzinger G, Azoulay E, Borges Sá M, Johnson EM, et al. Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis. Intensive Care Med. Jan 2009;35(1):55-62. [Medline].
Picazo JJ, González-Romo F, Candel FJ. Candidemia in the critically ill patient. Int J Antimicrob Agents. Nov 2008;32 Suppl 2:S83-5. [Medline].
Falcone M, Barzaghi N, Carosi G, Grossi P, Minoli L, Ravasio V, et al. Candida infective endocarditis: report of 15 cases from a prospective multicenter study. Medicine (Baltimore). May 2009;88(3):160-8. [Medline].
Shah CP, McKey J, Spirn MJ, et al. Ocular candidiasis: a review. Br J Ophthalmol. Apr 2008;92(4):466-8. [Medline].
Blot SI, Vandewoude KH, De Waele JJ. Candida peritonitis. Curr Opin Crit Care. Apr 2007;13(2):195-9. [Medline].
Vazquez JA, Sobel JD. Candidiasis. In: Clinical Mycology, Dismukes WE, Pappas PG, and Sobel JD, eds. Oxford Univers. 2003:143-87.
Eiland EH, Hassoun A, English T. Points of concern related to the micafungin versus caspofungin trial. Clin Infect Dis. Feb 15 2008;46(4):640-1; author reply 641. [Medline].
Alexander BD, Pfaller MA. Contemporary tools for the diagnosis and management of invasive mycoses. Clin Infect Dis. 2006;43:S15-S27.
Odabasi Z, Mattiuzzi G, Estey E, et al. Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis. Jul 15 2004;39(2):199-205. [Medline].
Shepard JR, Addison RM, Alexander BD, et al. Multicenter evaluation of the Candida albicans/Candida glabrata peptide nucleic acid fluorescent in situ hybridization method for simultaneous dual-color identification of C. albicans and C. glabrata directly from blood culture bottles. J Clin Microbiol. Jan 2008;46(1):50-5. [Medline].
[Guideline] 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].
[Guideline] Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis. Jan 15 2004;38(2):161-89. [Medline].
Chandrasekar PH, Sobel JD. Micafungin: a new echinocandin. Clin Infect Dis. Apr 15 2006;42(8):1171-8. [Medline].
Vazquez JA, Sobel JD. Anidulafungin: a novel echinocandin. Clin Infect Dis. Jul 15 2006;43(2):215-22. [Medline].
[Best Evidence] Nurbhai M, Grimshaw J, Watson M, et al. Oral versus intra-vaginal imidazole and triazole anti-fungal treatment of uncomplicated vulvovaginal candidiasis (thrush). Cochrane Database Syst Rev. Oct 17 2007;CD002845. [Medline].
Charlier C, Hart E, Lefort A, et al. Fluconazole for the management of invasive candidiasis: where do we stand after 15 years?. J Antimicrob Chemother. Mar 2006;57(3):384-410. [Medline].
Sobel JD, Revankar SG. Echinocandins--first-choice or first-line therapy for invasive candidiasis?. N Engl J Med. Jun 14 2007;356(24):2525-6. [Medline].
[Best Evidence] Reboli AC, Rotstein C, Pappas PG, et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. Jun 14 2007;356(24):2472-82. [Medline].
Kuse ER, Chetchotisakd P, da Cunha CA, 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].
[Best Evidence] Kullberg BJ, Sobel JD, Ruhnke M, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet. Oct 22-28 2005;366(9495):1435-42. [Medline].
Schuster MG, Edwards JE Jr, Sobel JD, Darouiche RO, Karchmer AW, Hadley S, et al. Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med. Jul 15 2008;149(2):83-90. [Medline].
Cornely OA, Lasso M, Betts R, et al. Caspofungin for the treatment of less common forms of invasive candidiasis. J Antimicrob Chemother. Aug 2007;60(2):363-9. [Medline].
Pachl J, Svoboda P, Jacobs F, et al. A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clin Infect Dis. May 15 2006;42(10):1404-13. [Medline].
Khan FA, Slain D, Khakoo RA. Candida endophthalmitis: focus on current and future antifungal treatment options. Pharmacotherapy. Dec 2007;27(12):1711-21. [Medline].
Kauffman CA. Clinical efficacy of new antifungal agents. Curr Opin Microbiol. Oct 2006;9(5):483-8. [Medline].
Sable CA, Strohmaier KM, Chodakewitz JA. Advances in antifungal therapy. Annu Rev Med. 2008;59:361-79. [Medline].
Ostrosky-Zeichner L, Oude Lashof AM, Kullberg BJ, et al. Voriconazole salvage treatment of invasive candidiasis. Eur J Clin Microbiol Infect Dis. Nov 2003;22(11):651-5. [Medline].
Skiest DJ, Vazquez JA, Anstead GM, et al. Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection. Clin Infect Dis. Feb 15 2007;44(4):607-14. [Medline].
Ullmann AJ, Cornely OA. Antifungal prophylaxis for invasive mycoses in high risk patients. Curr Opin Infect Dis. Dec 2006;19(6):571-6. [Medline].
van Burik JA, Ratanatharathorn V, Stepan DE, et al. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis. Nov 15 2004;39(10):1407-16. [Medline].
Husain S, Paterson DL, Studer S, et al. Voriconazole prophylaxis in lung transplant recipients. Am J Transplant. Dec 2006;6(12):3008-16. [Medline].
Pfaller MA, Pappas PG, Wingard JR. Invasive fungal pathogens: current epidemiological trends. Clin Infect Dis. Aug 1 2006;43 (Suppl 1):S3-S14. [Full Text].
Leleu G, Aegerter P, Guidet B. Systemic candidiasis in intensive care units: a multicenter, matched-cohort study. J Crit Care. Sep 2002;17(3):168-75. [Medline].
Zaoutis TE, Heydon K, Localio R, et al. Outcomes attributable to neonatal candidiasis. Clin Infect Dis. May 1 2007;44(9):1187-93. [Medline].
Cunha BA. Antibiotic Essentials. 9th ed. Sudbury, MA: Jones & Bartlett; 2010.
Further Reading
Bodey GP (Ed). Candidiasis. Pathogenesis, diagnosis and treatment. 2nd ed. New York, NY; Raven Press; 1993.
Calderone RA (Ed). Candida and candidiasis. Washington, DC; ASM Press; 2002.
NCCLS. Method for Antifungal Disk Diffusion Susceptibility Testing of Yeasts; Proposed Guideline. NCCLS document M44-P [ISBN 1-56238-488-0]. NCCLS, Pennsylvania, USA 2003
NCCLS. Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard-Second Edition. NCCLS document M27-A2 [ISBN 1-56238-469-4]. NCCLS, Pennsylvania, USA 2002.
Keywords
candidiasis, Candida albicans, C albicans, fungal infection, candidal infection, candidosis, fungus infection, Candida, mucocutaneous candidiasis, candidemia, disseminated candidiasis, candidal colonization, candidiasis syndromes, intertrigo, paronychia, onychomycosis, oral thrush, mucosal candidiasis, systemic candidiasis, hepatosplenic candidiasis, fungemia, granulocytopenia, oropharyngeal candidiasis, OPC esophageal candidiasis, vulvovaginal candidiasis, VVC, cutaneous candidiasis syndromes, chronic mucocutaneous candidiasis
Addison disease, membranous candidiasis, erythematous candidiasis, chronic atrophic candidiasis, nonesophageal gastrointestinal candidiasis, respiratory tract candidiasis, laryngeal candidiasis, genitourinary tract candidiasis, candidal endophthalmitis, intravascular catheter-related candidiasis, fungal endocarditis, renal candidiasis, Candida peritonitis, Candida esophagitis, Candida folliculitis, Candida balanitis, Candida cystitis, Candida tracheobronchitis, Candida pneumonia, Candida splenic abscess, Candida hypersplenism
Candida cholecystitis, Candida arthritis, Candida osteomyelitis, Candida costochondritis, Candida myositis, Candida myocarditis-pericarditis, Candida endocarditis fungal meningitis, Candida parapsilosis , C parapsilosis, Candida glabrata , C glabrata, Candida tropicalis , C tropicalis
Candida krusei , C krusei, Candida kefyr, C kefyr, Candida dubliniensis , C dubliniensis, Candida guilliermondi , C guilliermondi, Candida lusitaniae , C lusitaniae
