You are in: eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease CandidiasisArticle Last Updated: May 2, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Sabah Kalyoussef, DO, Staff Physician, Department of Pediatrics, Saint Peter's University Hospital Sabah Kalyoussef is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, American Osteopathic Association, and Medical Society of New Jersey Coauthor(s): Robert W Tolan Jr, MD, Chief of Allergy, Immunology and Infectious Diseases, The Children's Hospital at St Peter's University Hospital, Clinical Associate Professor of Pediatrics, Drexel University College of Medicine; Michael E Greenberg, MD, MPH, Clinical Instructor, Department of Pediatrics, University of California at San Francisco Editors: Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Mark R Schleiss, MD, American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota School of Medicine; Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine; Russell W Steele, MD, Professor and Vice Chairman, Department of Pediatrics, Head, Division of Infectious Diseases, Louisiana State University Health Sciences Center Author and Editor Disclosure Synonyms and related keywords: candidiasis, candidosis, monilia, thrush, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei, Candida lusitaniae, Candida stellatoidea. INTRODUCTIONSection 2 of 11
  BackgroundCandidal infections are extremely common. Candida albicans is the most common cause of human candidal infections, but other pathogenic species include C glabrata, C parapsilosis, C tropicalis, C krusei, C lusitaniae, and C stellatoidea. PathophysiologyInfections caused by Candida may affect numerous organ systems, such as the eyes, lungs, kidneys, heart, and central nervous system (CNS). Skin The most common manifestation of candidal infection is diaper dermatitis in infants. Candida organisms also can cause intertrigo in older individuals. Intertrigo has a predilection for dark moist areas, such as the groin or fat folds. Predisposing conditions include diabetes mellitus, obesity, and hyperhidrosis. Nails A chronic paronychia may be caused by one of several Candida species. Candida organisms also can cause onychomycosis, including total nail dystrophy due to chronic mucocutaneous candidiasis, a rare T-cell disorder. Mucous membranes Thrush, or oral candidiasis, also is common in infants. Oral candidiasis also may be an adverse effect from using inhaled corticosteroids for asthma due to oral deposition. Patients who are immunocompromised may suffer from candidal esophagitis as well as thrush. Genitals Vaginal yeast infections affect nearly 75% of women. Male partners may develop balanitis or balanoposthitis. Individuals with chronic indwelling catheters also are predisposed to recurrent candidal infections. Systemic Candida organisms can cause severe systemic infections in immunocompromised patients, compared to benign cutaneous or localized infections in the immunocompetent patient. Reports of systemic candidiasis are common in children with AIDS and other immune deficiencies, as well as in very low birth weight premature infants. Manifestations include fungemia, endophthalmitis, meningitis, renal or bladder bezoars, and arthritis. Virulence factors A number of factors can contribute to the likelihood of candidal infections. An intact skin barrier is protective. Candidal infections are promoted in the face of lymphocyte dysfunction, as is observed in persons with AIDS and those with chronic mucocutaneous candidiasis (CMCC). Adherence of Candida organisms to oral and vaginal epithelium is believed to be promoted by biologic factors (eg, fibronectin in thromboses) and by iatrogenic factors (eg, presence of plastic catheters, disruption of normal bacterial flora). In neonates, risk factors include indwelling catheters, prolonged antibiotic use, necrotizing enterocolitis, previous bloodstream infections, total parenteral nutrition, and low birth weight. Chronic mucocutaneous candidiasis CMCC is a heterogeneous group of disorders characterized by chronic candidal infections of the nails, skin, and mucous membranes. Most CMCC disorders are autosomal recessive and related to a mutation in the AIRE gene. Lymphocyte numbers are normal; however, response to in vitro exposure to candidal antigen is absent. FrequencyUnited StatesThrush occurs in approximately 2-5% of healthy newborns and a slightly higher percentage of infants in the first year of life. Vaginal candidal infections occur in approximately 75% of women, and 40-50% of women experience recurrence. Approximately 2-5% of premature infants weighing less than 1500 g develop disseminated disease. Mortality/MorbidityCandidal infections rarely cause significant morbidity in the healthy host. However, systemic disease may be found in as many as 15% of patients who are neutropenic. Mortality in low birth weight premature infants with systemic candidiasis may reach 50%. Candida is the second leading cause of sepsis in critical care patients. RaceNo racial predilection exists. SexVaginal candidosis is a frequent problem among women and adolescent girls. No gender predilection exists for other forms of candidiasis. AgeIn the healthy host, candidal infections are most common in the first year of life as thrush or diaper dermatitis. Vulvovaginitis is more common in adolescent and adult females. CLINICALSection 3 of 11
History
Physical
CausesCandidal infections have differing presentations in patients who are immunocompetent versus persons who are immunocompromised.
DIFFERENTIALSSection 4 of 11
Diaper Dermatitis Endocarditis, Fungal Fungal Infections in Preterm Infants
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| Drug Name | Nystatin oral suspension (Nilstat) |
|---|---|
| Description | DOC for oral candidiasis. Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei. |
| Adult Dose | 4-6 mL (ie, 400,000-600,000 U) PO swish and spit qid until 48 h after lesions resolve |
| Pediatric Dose | Premature infants: 0.25-0.5 mL to each side of mouth qid until 48 h after lesions resolve Infants: 1 mL to each side of mouth qid until 48 h after lesions resolve Children: 2-3 mL to each side of mouth qid until 48 h after lesions resolve 1 mL=100,000 U |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Safe in breastfeeding because oral suspension is absorbed poorly |
| Drug Name | Gentian violet |
|---|---|
| Description | Effective as second-line agent for oral candidiasis resistant to nystatin. |
| Adult Dose | Apply to affected areas tid |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Stains skin and clothing |
These agents are used to treat cutaneous candidiasis.
| Drug Name | Nystatin cream (Mycostatin, Nilstat) |
|---|---|
| Description | DOC in cutaneous candidiasis. |
| Adult Dose | 100,000 U/g; apply bid/qid to affected areas until 48 h after resolution of lesions |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Not for treatment of systemic fungal infections; avoid contact with eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy |
| Drug Name | Clotrimazole 1% cream (Lotrimin, Mycelex) |
|---|---|
| Description | Second-line agent in treatment of cutaneous candidiasis. |
| Adult Dose | Apply to affected area bid until 48 h after resolution of lesions |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Not for treatment of systemic fungal infections; avoid contact with eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy |
| Drug Name | Miconazole 2% cream (Absorbine, Micatin) |
|---|---|
| Description | Alternate topical antifungal. Lotion is preferred in intertriginous areas. If cream is used, apply sparingly to avoid maceration effects. |
| Adult Dose | Apply to affected areas bid until 48 h after resolution of lesions |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | If sensitivity or chemical irritation occurs, discontinue use; use only externally; avoid contact with eyes |
These agents are used for treatment of cutaneous infections refractory to treatment by topical agents or as adjunctive therapy for systemic candidal infection.
| Drug Name | Fluconazole oral (Diflucan) |
|---|---|
| Description | Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. |
| Adult Dose | Vulvovaginitis: 150 mg PO once Oropharyngeal and esophageal candidiasis: 200 mg PO on day 1, followed by 100 mg qd for subsequent d |
| Pediatric Dose | Oropharyngeal candidiasis: 6 mg/kg PO on day 1, followed by 3 mg/kg/d for subsequent d Some older children may have clearances similar to that of adults; absolute doses not to exceed 600 mg/d Systemic candidal infections: 6-12 mg/kg/d |
| Contraindications | Documented hypersensitivity |
| Interactions | Inhibits CYP2C19 and 3A4; levels may increase with hydrochlorothiazides; levels may decrease with chronic coadministration of rifampin; coadministration may decrease phenytoin clearance; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with coadministration; increases in cyclosporine concentrations may occur when administered concurrently |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Adjust dose for renal insufficiency; monitor closely if rashes develop 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 for mothers who are breastfeeding |
| Drug Name | Itraconazole (Sporanox) |
|---|---|
| Description | Effective oral systemic antifungal. Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP450-dependent synthesis of ergosterol, a vital component of fungal cell membranes. |
| Adult Dose | Oral candidiasis: 100 mg PO qd for 15 d Vulvovaginitis: 200 mg PO bid for 1-3 d |
| Pediatric Dose | 3-5 mg/kg/d PO divided qd/bid |
| Contraindications | Documented hypersensitivity; coadministration with cisapride may cause adverse cardiovascular effects (possibly death); coadministration with alprazolam and triazolam |
| Interactions | Potent inhibitor of CYP3A4; antacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; may increase tacrolimus and cyclosporine plasma concentrations when high doses are used; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin or simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death; may increase digoxin levels; coadministration may increase plasma levels of midazolam, alprazolam, or triazolam; phenytoin and rifampin may reduce itraconazole levels (phenytoin metabolism may be altered) |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | May cause nausea, vomiting, diarrhea, hypokalemia, and elevated transaminases; hepatic metabolism; does not penetrate CSF well |
| Drug Name | Ketoconazole (Nizoral) |
|---|---|
| Description | Well absorbed orally. Administer with food to reduce nausea and vomiting. Imidazole broad-spectrum antifungal agent. Inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death. |
| Adult Dose | Superficial candidal infection (oral, vaginal, esophageal): 200 mg PO qd for 1-2 wk |
| Pediatric Dose | >2 years: 3.3-6.6 mg/kg/d PO qd |
| Contraindications | Documented hypersensitivity; fungal meningitis |
| Interactions | Potent inhibitor of CYP3A4; isoniazid may decrease bioavailability; coadministration decreases effects of either rifampin or ketoconazole; may increase effect of anticoagulants; may increase toxicity of corticosteroids and cyclosporine (cyclosporine dosage can be adjusted); may decrease theophylline levels |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| 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 |
| Drug Name | Flucytosine (Ancobon) |
|---|---|
| Description | Also known as 5-FC. Converted to fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against Candida and Cryptococcus species and generally used in combination with amphotericin B. |
| Adult Dose | 50-150 mg/kg/d PO divided q6h |
| Pediatric Dose | Neonates: 80-160 mg/kg/d PO divided q6h Children: 50-150 mg/kg/d PO divided q6h |
| Contraindications | Documented hypersensitivity |
| Interactions | Amphotericin B may increase toxicity of flucytosine; cytosine may inactivate flucytosine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Monitor CBC count, creatinine, alkaline phosphatase, AST, and ALT; may cause anemia, leukopenia, or thrombocytopenia; therapeutic levels 25-100 mg/L; adjust dose in renal failure |
| Drug Name | Posaconazole (Noxafil) |
|---|---|
| Description | 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 due to severe immunosuppression. |
| Adult Dose | 200 mg (5 mL) PO tid with food or liquid nutritional supplement to enhance absorption |
| Pediatric Dose | <13 years: Not established >13 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; coadministration with ergot alkaloids; coadministration with CYP3A4 substrates likely to result in serious toxicities (eg, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine) |
| Interactions | 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) |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| 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 |
The mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.
| Drug Name | Fluconazole IV (Diflucan) |
|---|---|
| Description | Second-line agent for treatment of systemic candidal infection. |
| Adult Dose | 400 mg IV as loading dose followed by 200 mg IV qd |
| Pediatric Dose | Neonates: 6-12 mg/kg IV as loading dose followed by 3-6 mg/kg/d qd Children: 10 mg/kg IV loading dose followed by 3-6 mg/kg/d qd |
| Contraindications | Documented hypersensitivity |
| Interactions | Inhibits CYP3A4, thus increasing levels of CYP3A4 substrates (eg, may increase risk of cardiac arrhythmias by cisapride, astemizole); levels may increase with hydrochlorothiazides; levels may decrease with chronic coadministration of rifampin; coadministration may decrease phenytoin concentrations; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with coadministration; increases in cyclosporine concentrations may occur when administered concurrently |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Adjust dose for renal insufficiency; monitor closely if rashes develop 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 for mothers who are breastfeeding |
| Drug Name | Amphotericin B, liposome (AmBisome) |
|---|---|
| Description | Amphotericin B in a 10% lipid emulsion appears to have less nephrotoxicity than standard preparation of amphotericin. Lipid emulsion does not appear to decrease antifungal properties of amphotericin B. |
| Adult Dose | 5 mg/kg IV as single infusion administered no faster than 2.5 mg/kg/h |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antineoplastic agents or other nephrotoxic drugs (eg, aminoglycosides, cyclosporine) may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Although less nephrotoxic than standard amphotericin preparations, use caution in patients with decreased renal function; monitor BUN and creatinine levels; LFT, electrolytes, and CBC count; may require premedication with antihistamines, corticosteroids or analgesics to decrease risk of headache, chills, fever, or rigors |
| Drug Name | Amphotericin B desoxycholate (Amphocin, Fungizone) |
|---|---|
| Description | DOC for treatment of systemic fungal infections. Polyene antibiotic produced by strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols (eg, ergosterol) in fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death. Premedication with acetaminophen may help reduce rigors, chills, and fever associated with infusion. Hydrocortisone directly added to infusate also may reduce febrile reactions. |
| Adult Dose | Test dose: 1 mg IV administered over 30 min Initial dose: 0.25-0.5 mg/kg/d IV qd/qod administered over 2-6 h Increment: Increase as tolerated by 0.25-0.5 mg/kg/d Maintenance: 0.25-1 mg/kg/d or 1-1.5 mg/kg qod |
| Pediatric Dose | Test dose: 0.1 mg/kg IV, not to exceed 1 mg; administer over 20-60 min Initial dose: 0.25-0.5 mg/kg/d IV qd/qod administered over 2-6 h Increment: Increase as tolerated by 0.25-0.5 mg/kg/d Maintenance: 0.25-1 mg/kg/d or 1-1.5 mg/kg qod |
| Contraindications | Documented hypersensitivity |
| Interactions | Antineoplastic agents or other nephrotoxic drugs (eg, aminoglycosides, cyclosporine) may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for > 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients who are neutropenic and who are receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are common after first few administrations, premedication with antihistamines, corticosteroids, and analgesics may diminish reaction; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock |
| Drug Name | Caspofungin (Cancidas) |
|---|---|
| Description | First of a new class of antifungal drugs (glucan synthesis inhibitors). Inhibits synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall. |
| Adult Dose | 50 mg IV qd |
| Pediatric Dose | 1 mg/kg/d qd for the first 2 d then 2 mg/kg/d qd thereafter has been used for neonates in early studies |
| Contraindications | Documented hypersensitivity |
| Interactions | 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) |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in moderate hepatic dysfunction (ie, decrease dose to 35 mg/d); may exacerbate pre-existing renal dysfunction or myelosuppression |
| Media file 1: Typical appearance of thrush. Note multiple white plaques on lips, gingivae, tongue, and palate. | |
 | View Full Size Image | Media type: Photo |
| Media file 2: Candidal diaper dermatitis. Note satellite papules and involvement of intertriginous folds. | |
 | View Full Size Image | Media type: Photo |
Article Last Updated: May 2, 2007
