eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Candidiasis

Sabah Kalyoussef, DO, Fellow in Pediatric Infectious Diseases, Children's Hospital at Montefiore
Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint 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

Updated: Nov 20, 2008

Introduction

Background

Candidal infections are extremely common. Candida albicans is the most common cause of human candidal infections,¹ but other pathogenic species include Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei, Candida lusitaniae, and Candida stellatoidea.

Pathophysiology

Infections caused by Candida may affect numerous organ systems, such as the eyes, lungs, kidneys, heart, and CNS.

Skin

The most common manifestation of candidal infection is diaper dermatitis in infants. Candida organisms can also 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 can also cause onychomycosis, including total nail dystrophy due to chronic mucocutaneous candidiasis (CMCC), a rare T-cell disorder.

Mucous membranes

Thrush, or oral candidiasis, is also common in infants. Oral candidiasis may also 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 are also predisposed to recurrent candidal infections.

Systemic

Candida organisms can cause severe systemic infections in immunocompromised patients, compared with benign cutaneous or localized infections in immunocompetent patients. Reports of systemic candidiasis are common in children with acquired immunodeficiency syndrome (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

Numerous 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 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.

Frequency

United States

Thrush 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/Morbidity

Candidal 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.

Race

No racial predilection is noted.

Sex

Vaginal candidosis is a frequent problem among women and adolescent girls. No gender predilection is noted in other forms of candidiasis.

Age

In 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.

Clinical

History

Thrush: Infants with thrush may experience pain, poor feeding, or fussiness.
Cutaneous candidiasis
- Patients with cutaneous candidiasis experience itching, burning, and soreness.
- Most commonly affected areas are the diaper area in infants and toddlers and abdominal fat folds and groin in older individuals.
Paronychia and onychomycosis
- Candidal paronychia and nail disease has a predilection for the fingernails.
- Paronychia is usually painful.
Vulvovaginitis
- Most women with vulvovaginitis complain of a creamy vaginal discharge with soreness and burning.
- Dyspareunia is often present.
Otitis externa
- Otitis externa is found most commonly in tropical and subtropical climates.
- Malnutrition and immunosuppression are risk factors.
- Candidiasis is clinically difficult to distinguish from other causes of otitis externa.
GI candidiasis
- GI candidiasis is primarily observed in individuals who are immunocompromised, especially in persons with human immunodeficiency virus (HIV) infection and/or primary immunodeficiency.
- This may be a cause of chronic diarrhea.
- Common in infants, glossitis may occur in older children following use of broad-spectrum antibiotics or may signal immunodeficiency.
- Esophagitis should be suspected in individuals who are immunocompromised when oral candidiasis is present. Symptoms include dysphagia and odynophagia. Risk of esophagitis is elevated in children taking H2 blockers.
Pneumonia: This is extremely rare and usually results from disseminated disease.
Cystitis: Risk factors for cystitis include indwelling urinary catheters, immunosuppression, diabetes mellitus, and use of broad-spectrum antibiotics.
Endophthalmitis
- Endophthalmitis is the most common intraocular infection in newborns.
- Risk factors include low birth weight and prolonged hospitalization.
CNS infections
- CNS infections usually present as subacute meningitis.
- Risk factors include indwelling catheters (especially shunts), prematurity, malnutrition, immunodeficiency, and organ transplantation.
Endocarditis: Risk factors for endocarditis include immunosuppression, HIV infection, intravenous catheters, corticosteroid use, prolonged hospitalization, and use of broad-spectrum antibiotics.
Hepatic (hepatosplenic) candidiasis
- Risk factors include neutropenia.
- Hepatic candidiasis may present with fever of unknown origin. It is usually a manifestation of disseminated candidiasis.

Physical

Thrush
- White plaques are observed in the mouth and may affect the lips, tongue, gums, and palate.
- Scraping of the lesions may reveal erythema and bleeding at the base (see Media file 1). The plaques do not scrape off easily.
Cutaneous candidiasis
- Lesions consist of beefy-red plaques, often with scalloped borders.
- Satellite papules and pustules may be observed surrounding the plaques.
- Maceration is often present, especially in intertriginous areas (see Media file 2).
- Candidal diaper dermatitis is generally confluent in intertriginous areas, whereas generic diaper dermatitis may demonstrate sparing in the folds.
Paronychia and onychomycosis
- Paronychia typically involves the cuticular fold of fingernails, causing redness, swelling, and pain.
- Pus may be present.
- Nail involvement usually stems from long-standing paronychia and causes a yellow discoloration of the nail, often with separation of the nail from the nail bed.
Genital candidiasis
- With vulvovaginitis, a creamy white discharge is usually present. White plaques may be observed on an erythematous base of the vaginal mucosa or vulvar skin. Papules and pustules may be present.
- With balanitis, lesions are usually observed on the glans penis and consist of erythematous plaques, pustules, or erosions.
GI disease
- Glossitis is characterized by creamy or curdlike white plaques, which may be painful and bleed beneath when scraped.
- With esophagitis, oral candidiasis may or may not be present. Weight loss is common.
Otitis externa
- Tenderness of the pinna, aural discharge, and erythema characterize otitis externa.
- Lymphadenopathy of postauricular or preauricular nodes may be present.
- A grayish membrane may be present in the canal.
Hepatic candidiasis: This infection usually presents as abscesses in the liver and/or spleen.
Endocarditis
- Endocarditis is characterized by fever and a new or changing heart murmur.
- Symptoms relating to embolization to other organs (eg, CNS, kidneys, lungs, retina and choroid, skin) may be present.
Endophthalmitis
- White well-circumscribed lesions of the retina and choroid in the posterior pole characterize endophthalmitis.
- Isolation of candida from blood, urine, or other sources supports the diagnosis of endophthalmitis.
CNS infections
- Signs consistent with meningitis are often present with CNS infections.
- Evidence of candidal infection of other organ systems may be present.

Causes

Candidal infections have differing presentations in patients who are immunocompetent versus persons who are immunocompromised.

Patient who is immunocompetent
- Although candidal diaper rash is common in healthy infants, predisposing factors causing candidal infections in older individuals are often present.
- The most common factor is the disruption of normal flora following a course of antibiotic therapy, which is most commonly observed as cutaneous candidiasis or vulvovaginitis.
- Other risk factors for candidal infection relate to impaired immune function, including individuals with diabetes mellitus, premature infants, hosts who are immunocompromised, and persons using systemic or topical corticosteroids.
- Other risk factors include obesity, heat, and excessive sweating.
Patient who is immunocompromised
- Individuals who are immunocompromised are more susceptible to oral and cutaneous candidiasis and often have a more severe course.
- Oral candidiasis may appear as acute or chronic atrophic candidiasis, which causes painful red erosions of the tongue and mucous membranes.
- Candida species are frequent causes of central venous catheter infections.
- Immunosuppression may also cause systemic candidiasis, which may present as fungemia or funguria. Candida species may cause fungal bezoars in the kidney or bladder, or candidiasis may cause abscesses in the liver or spleen. Candidal meningitis, arthritis, and endophthalmitis all have been reported.
Neonates
- Neonates with very low birth weight are at a higher risk of developing candidemia.
- Risk factors include low birth weight, broad spectrum antibiotic use, total parental nutrition, previous bloodstream infections, or necrotizing enterocolitis.
Chronic mucocutaneous candidiasis (CMCC): CMCC is a cluster of disorders of cell-mediated immunity that presents as chronic severe candidal infections of the skin and mucous membranes.

Differential Diagnoses

Diaper Dermatitis
Endocarditis, Fungal
Fungal Infections in Preterm Infants

Workup

Laboratory Studies

The following studies are indicated in candidiasis:

Potassium hydroxide (KOH) slide preparation: Scrapings of oral or cutaneous lesions may demonstrate budding yeasts with pseudohyphae.
Cultures
- Blood culture is highly insensitive; fewer than 15% of patients with disseminated disease have positive blood cultures.
- Urine culture is often positive in individuals who are immunocompromised and have renal or bladder disease.
- Culture intravascular devices, especially indwelling catheters and especially in neonates suspected of having sepsis.
Alpha-glucan assay - Component of fungal cell wall
D-arabinatol assay - Measures fungal metabolite

Imaging Studies

Ultrasonography and CT scanning may be helpful in making the diagnosis of disseminated candidal infection in the individual who is immunocompromised, especially for renal, bladder, hepatic, and splenic lesions.
Endoscopy may be indicated for diagnosis of candidal esophagitis, especially when empiric treatment has failed.

Procedures

Lumbar puncture is indicated for patients suspected of having candidal meningitis. Findings may include the following:
- Elevated opening pressure
- Increased WBC count, often with predominance of lymphocytes
- Hyphae, which may be observed on Gram stain

Treatment

Medical Care

Treatment of candidal infections is primarily accomplished with appropriate antifungal drugs.²

Surgical Care

Remove the offending catheter in central venous catheter infection because attempts to treat the infection without its removal are largely unsuccessful and are accompanied by high morbidity and mortality.

Consultations

Consult an infectious disease specialist for patients suspected of having systemic candidal infections, especially in the host who is immunocompromised, and consult an ophthalmologist for suspected endophthalmitis in neonates.

Diet

No specific diet is required.

Activity

No restrictions are required.

Medication

Candidal infections are sensitive to a broad range of antifungal agents. Nystatin and one of the imidazoles are the most commonly used agents for oral or cutaneous candidiasis. Noting the resistance pattern in your area is important; fluconazole-resistant Candida has been reported. New antifungals include the echinocandins (eg, caspofungin, micafungin, anidulafungin). The mechanism of action of this group is to interfere with the cell wall integrity inhibiting 1,3 alpha-D-glucan synthase. Caspofungin has recently been approved by the US Food and Drug Administration (FDA) for use in the pediatric population.

Topical antifungals (oral preparations)

These agents are used for the treatment of oral candidiasis (thrush).

Nystatin oral suspension (Nilstat)

DOC for PO candidiasis. Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei.

Dosing

Adult

4-6 mL (ie, 400,000-600,000 U) PO swish and spit qid until 48 h after lesions resolve

Pediatric

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

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Safe in breastfeeding because PO susp is poorly absorbed

Gentian violet

Effective as second-line agent for PO candidiasis resistant to nystatin.

Dosing

Adult

Apply to affected areas tid

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

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

Stains skin and clothing

Topical antifungals (dermatologic)

These agents are used to treat cutaneous candidiasis.

Nystatin cream (Mycostatin, Nilstat)

DOC in cutaneous candidiasis. Each gram of cream contains 100,000 U.

Dosing

Adult

Apply bid/qid to affected areas until 48 h after resolution of lesions

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

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 eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy

Clotrimazole 1% cream (Lotrimin, Mycelex)

Second-line agent in treatment of cutaneous candidiasis.

Dosing

Adult

Apply to affected area bid until 48 h after resolution of lesions

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

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 eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy

Miconazole 2% cream (Absorbine, Micatin)

Alternate topical antifungal. Lotion is preferred in intertriginous areas. If cream is used, apply sparingly to avoid maceration effects.

Dosing

Adult

Apply to affected areas bid until 48 h after resolution of lesions

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

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

Systemic antifungals (oral)

These agents are used for treatment of cutaneous infections refractory to treatment by topical agents or as adjunctive therapy for systemic candidal infection.

Fluconazole oral (Diflucan)

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.

Dosing

Adult

Vulvovaginitis: 150 mg PO once
Oropharyngeal and esophageal candidiasis: 200 mg PO on day 1, followed by 100 mg once daily

Pediatric

Oropharyngeal candidiasis: 6 mg/kg PO on day 1, followed by 3 mg/kg/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

Interactions

Inhibits CYP2C19 and 3A4; levels may increase with hydrochlorothiazide; 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

Contraindications

Documented hypersensitivity

Precautions

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; 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

Itraconazole (Sporanox)

Effective PO 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.

Dosing

Adult

Oral candidiasis: 100 mg PO once daily for 15 d Vulvovaginitis: 200 mg PO bid for 1-3 d

Pediatric

3-5 mg/kg/d PO divided qd/bid

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)

Contraindications

Documented hypersensitivity; coadministration with cisapride may cause adverse cardiovascular effects (possibly death); coadministration with alprazolam and triazolam

Precautions

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

May cause nausea, vomiting, diarrhea, hypokalemia, and elevated transaminases; hepatic metabolism; does not penetrate CSF well

Ketoconazole (Nizoral)

Well absorbed PO. 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.

Dosing

Adult

Superficial candidal infection (PO, vaginal, esophageal): 200 mg PO once daily for 1-2 wk

Pediatric

<2 years: Not established
>2 years: 3.3-6.6 mg/kg/d PO once daily

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

Contraindications

Documented hypersensitivity; fungal meningitis

Precautions

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

Flucytosine (Ancobon)

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.

Dosing

Adult

50-150 mg/kg/d PO divided q6h

Pediatric

Neonates: 80-160 mg/kg/d PO divided q6h
Children: 50-150 mg/kg/d PO divided q6h

Interactions

Amphotericin B may increase toxicity of flucytosine; cytosine may inactivate flucytosine

Contraindications

Documented hypersensitivity

Precautions

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

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

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 due to severe immunosuppression.

Dosing

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

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)

Contraindications

Documented hypersensitivity; coadministration with ergot alkaloids; coadministration with CYP3A4 substrates likely to result in serious toxicities (eg, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine)

Precautions

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

Voriconazole oral (Vfend)

Used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or Scedosporium apiospermum infections. A triazole antifungal agent that inhibits fungal CYP450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.

Dosing

Adult

<40 kg: 100 mg PO q12h, may increase to 150 mg q12h if inadequate response
>40 kg: 200 mg PO q12h, may increase to 300 mg q12h if inadequate response

Pediatric

Not established; limited data suggest initial maintenance dose of 3-5 mg/kg/dose PO q12h for children <25 kg

Interactions

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), other may need more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG CoA inhibitors, benzodiazepines, calcium channel blockers)

Contraindications

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

Precautions

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

Systemic antifungals (intravenous)

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.

Fluconazole IV (Diflucan)

Second-line agent for treatment of systemic candidal infection.

Dosing

Adult

400 mg IV as loading dose followed by 200 mg IV once daily

Pediatric

Neonates: 6-12 mg/kg IV as loading dose followed by 3-6 mg/kg/d once daily
Children: 10 mg/kg IV loading dose followed by 3-6 mg/kg/d once daily

Interactions

Inhibits CYP3A4, thus increasing levels of CYP3A4 substrates (eg, may increase risk of cardiac arrhythmias by cisapride, astemizole); levels may increase with hydrochlorothiazide; 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

Contraindications

Documented hypersensitivity

Precautions

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

Amphotericin B, liposome (AmBisome)

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.

Dosing

Adult

5 mg/kg IV as single infusion administered no faster than 2.5 mg/kg/h

Pediatric

Administer as in adults

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

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

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

Amphotericin B desoxycholate (Amphocin, Fungizone)

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.

Dosing

Adult

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

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

Interactions

Contraindications

Documented hypersensitivity

Precautions

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 (eg, magnesium, potassium), LFT, CBC count, 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

Caspofungin (Cancidas)

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.

Dosing

Adult

50 mg IV qd

Pediatric

<3 months: Not established
3 months to 17 years:
Loading dose: 70 mg/m² IV infused over 1 h on day 1
Maintenance: 50 mg/m²/d IV infused over 1 h
>18 years: Administer as in adults

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)

Contraindications

Documented hypersensitivity

Precautions

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 pre-existing renal dysfunction or myelosuppression

Voriconazole IV (Vfend)

Dosing

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, may switch to PO; if inadequate response, may increase to 300 mg q12h

Pediatric

Not established; in 2 reviews, the dosing recommended for invasive fungal disease was 6 mg/kg IV q12h for 2 doses, then 4 mg/kg IV q12h
Doses up to 8 mg/kg have also been used
>12 years: Administer as in adults

Interactions

Contraindications

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Follow-up

Transfer

Transfer of patients with candidiasis is appropriate if the required level of care is not locally available.

Deterrence/Prevention

The risk of candidal diaper rash may be reduced by preventing irritant diaper dermatitis by using absorbent diapers and preventing excessive exposure to urine or feces.
Encourage parents to appropriately clean their infant's bottles while they are treated for thrush.
Encourage asthma patients to rinse their mouth after using their corticosteroid inhaler.
Keep hands dry; when wet work is unavoidable, use rubber gloves with cotton liners. Response is generally quite good to topical azoles.
Cutaneous candidiasis may be prevented by keeping areas cool and dry and by using breathable fabrics (eg, cotton).
Fluconazole is used extensively in patients with neutropenia, persons undergoing organ transplantation, and in extremely low birth weight infants.^3,4,5,6,7,8 Although found to be generally safe in these populations and able to reduce candidal colonization, effect on survival has been minimal. New studies show prophylactic doses of fluconazole given in the newborn intensive care setting may prevent candidemia and colonization in high-risk patients.

Prognosis

Prognosis for oral or cutaneous candidiasis is excellent with appropriate medical treatment.
Systemic candidiasis, especially in low birth weight premature infants, carries a high rate of morbidity and mortality. Even with appropriate treatment, mortality may reach 50% in this population.

Patient Education

For excellent patient education resources, visit eMedicine's Yeast and Fungal Infections Center; Children's Health Center; and Skin, Hair, and Nails Center. Also, see eMedicine's patient education articles Candidiasis (Yeast Infection), Yeast Infection Diaper Rash, and Yeast Infection Skin Rash.

Miscellaneous

Medicolegal Pitfalls

Candidiasis in an individual without known risk factors (eg, infant, immunocompromised state, diabetes, obesity) should prompt a search for such factors, especially immunodeficiency and HIV infection.

Multimedia

Media file 1: Typical appearance of thrush. Note multiple white plaques on lips, gingivae, tongue, and palate.

Media file 2: Candidal diaper dermatitis. Note satellite papules and involvement of intertriginous folds.

References

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Kicklighter SD, Springer SC, Cox T, et al. Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infant. Pediatrics. Feb 2001;107(2):293-8. [Medline].
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Mondal RK, Singhi SC, Chakrabarti A, M J. Randomized comparison between fluconazole and itraconazole for the treatment of candidemia in a pediatric intensive care unit: a preliminary study. Pediatr Crit Care Med. Nov 2004;5(6):561-5. [Medline].
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Keywords

candidiasis, candidosis, monilia, thrush, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei, Candida lusitaniae, Candida stellatoidea, candidal infections, diaper dermatitis, intertrigo, diabetes mellitus, obesity, hyperhidrosis, total nail dystrophy, esophagitis, vaginal yeast infection, balanitis, balanoposthitis, acquired immunodeficiency syndrome, AIDS, very low birth weight premature infants, fungemia, endophthalmitis, meningitis, renal bezoars, arthritis, chronic mucocutaneous candidiasis, CMCC, necrotizing enterocolitis, vaginal candidosis, vulvovaginitis, cutaneous candidiasis, paronychia, onychomycosis, otitis externa, glossitis, hepatic candidiasis, liver abscesses, endocarditis

Contributor Information and Disclosures

Author

Sabah Kalyoussef, DO, Fellow in Pediatric Infectious Diseases, Children's Hospital at Montefiore
Sabah Kalyoussef, DO 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
Disclosure: Nothing to disclose.

Coauthor(s)

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching

Michael E Greenberg, MD, MPH, Clinical Instructor, Department of Pediatrics, University of California at San Francisco
Michael E Greenberg, MD is a member of the following medical societies: Alpha Omega Alpha, Ambulatory Pediatric Association, American Academy of Pediatrics, and American Public Health Association
Disclosure: Nothing to disclose.

Medical Editor

Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine
Itzhak Brook, MD, MSc is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Immunocompromised Host Society, International Society for Infectious Diseases, Medical Society of the District of Columbia, New York Academy of Sciences, Pediatric Infectious Diseases Society, Society for Ear, Nose and Throat Advances in Children, Society for Experimental Biology and Medicine, Society for Pediatric Research, Southern Medical Association, and Surgical Infection Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

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
Mark R Schleiss, MD is a member of the following medical societies: American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting; Pfizer Honoraria Consulting

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

Further Reading

eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Candidiasis

Introduction

Background

Pathophysiology

Frequency

United States

Mortality/Morbidity

Race

Sex

Age

Clinical

History

Physical

Causes

Differential Diagnoses

Other Problems to Be Considered

Workup

Laboratory Studies

Imaging Studies

Procedures

Treatment

Medical Care

Surgical Care

Consultations

Diet

Activity

Medication

Topical antifungals (oral preparations)

Nystatin oral suspension (Nilstat)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Gentian violet

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Topical antifungals (dermatologic)

Nystatin cream (Mycostatin, Nilstat)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Clotrimazole 1% cream (Lotrimin, Mycelex)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Miconazole 2% cream (Absorbine, Micatin)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Systemic antifungals (oral)

Fluconazole oral (Diflucan)

Dosing

Adult

Pediatric