AUTHOR INFORMATION

Section 1 of 12

Authored by Tarlan Hedayati, MD, Instructor of Clinical Emergency Medicine, Director of Observation Unit, Director of Chest Pain Unit, Department of Emergency Medicine, Los Angeles County/University of Southern California Medical Center

Coauthored by Renee N Magana, MD, Consulting Staff, Department of Emergency Medicine, Sherman Oaks Hospital; Consulting Staff, Department of Emergency Medicine, Valley Presbyterian Hospital

Tarlan Hedayati, MD, is a member of the following medical societies: American Academy of Emergency Medicine

Edited by David FM Brown, MD, Assistant Professor, Department of Medicine, Division of Emergency Medicine, Harvard Medical School; Vice-Chair, Department of Emergency Medicine, Massachusetts General Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Barry J Sheridan, DO, Chief, Department of Emergency Medical Services, Brooke Army Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School

Author's Email:	Tarlan Hedayati, MD
Editor's Email:	David FM Brown, MD

eMedicine Journal, September 28 2006, VOLUME 7, Number 9

INTRODUCTION

Section 2 of 12

Background: Candida species are ubiquitous fungi found throughout the world as normal body flora. Unfortunately, candidiasis is also the most common mycotic infection, causing a variety of diseases. Candidiasis can range from superficial disorders such as diaper rash to invasive, rapidly fatal infections in immunocompromised hosts. Candida albicans is commonly responsible for candidiasis, but others, such as Candida tropicalis, Candida parapsilosis, Candida guilliermondi, and Torulopsis glabrata are also causative organisms.

Pathophysiology: Candidiasis affects a wide variety of organ systems. In immunocompetent persons, any warm, moist part of the body exposed to the environment is susceptible to infection. Common examples of this are vaginitis; vulvar rash; oral thrush; conjunctivitis; endophthalmitis; diaper rash; and infections of the nail, rectum, and other skin folds. In immunocompromised patients, systemic illnesses such as myocarditis, hepatosplenic abscess, pulmonary infection, CNS infection, and chronic disease may occur.

Frequency:

• In the US: Candida species are ubiquitous and colonize over 50% of healthy individuals. Up to 14% of patients with immunocompromising disease develop systemic candidiasis. C albicans is the most common cause of esophagitis.

• Internationally: In countries where other fungi are endemic, Candida species have replaced Cryptococcus species as the most common fungi affecting the CNS of immunocompromised patients worldwide.

Mortality/Morbidity: Most candidal infections are superficial and are associated with a benign course and full recovery. However, in immunocompromised hosts, systemic illness is associated with death in as many as 77%.

Sex: Males and females are affected equally by most forms of Candida species.

• In women, candidal infection is the second most common cause of vaginitis.

• In either sex, chronic yeast infections, caused by Candida species, are common first symptoms of HIV infection.

Age: Candida species are a part of normal flora and can affect people of any age.

• Neonates commonly have perianal infection (diaper rash) and oral thrush.

• In adults, oral candidiasis increases in incidence with age; the elderly are affected most.

• Gastrointestinal (GI) candidiasis also increases in incidence with age.

CLINICAL

Section 3 of 12

History:

• Pruritus

• Dry mouth and tongue, cracked tongue, bleeding gums

• Recurrent urinary tract infections (UTIs)

• Dysuria or frequency

• Vaginal burning, itching, or discharge or painful intercourse

• Unusual menstrual cramping

• Dysphagia

• Indigestion or heartburn

• Abdominal pain, bloating, or gas

• Constipation, diarrhea, or mucus in the stool

• Depression, anxiety, sudden mood swings, lack of concentration, headaches, drowsiness, or fatigue

• Muscle and/or joint pain and swelling

Physical:

• Discrete or confluent white plaques on oral mucosa (ie, thrush)

  • Most common in the mouth and on the tongue

  • Usually painless unless fissures extend to the corners of the mouth

• Red macerated intertriginous areas; white pustules may be present.

• Vulvovaginitis - Pruritic discharge, often described as white and "cheesy"

• GI tract candidiasis - One or multiple shallow ulcerations

• Systemic candidiasis

• Fever

• Retinal abscesses

Causes: Candida species typically are the cause. Most infections are caused by C albicans, although C tropicalis, Candida lusitaniae, Candida krusei, and other species may be involved.

DIFFERENTIALS

Section 4 of 12

Dermatitis, Contact
Dermatitis, Exfoliative
Encephalitis
Endocarditis
Esophagitis
Herpes Simplex
Herpes Simplex Encephalitis
Pityriasis Rosea
Pneumonia, Aspiration
Pneumonia, Bacterial
Pneumonia, Immunocompromised
Pneumonia, Mycoplasma
Pneumonia, Viral
Urinary Tract Infection, Female
Urinary Tract Infection, Male
Vaginitis
Vulvovaginitis
Wernicke Encephalopathy

Other Problems to be Considered:

Folliculitis
Acute peritonitis
Tracheitis

WORKUP

Section 5 of 12

Lab Studies:

• Vaginal and cutaneous candidiasis

• Wet mount: Scrapings obtained from skin, nails, or oral or vaginal mucosa may be examined under a microscope for pseudohyphae.

• Potassium hydroxide (KOH) smear: Scrapings are treated with KOH to demonstrate pseudohyphae more readily.

• Culture from skin scrapings is nonspecific.

• Systemic candidiasis (eg, CNS, joint, blood)

• Cultures of cerebrospinal fluid (CSF), joint fluid, urine, or surgical specimens may be obtained to identify candidal infections.

• Blood culture is useful for diagnosing endocarditis and catheter-induced sepsis.

• Urinalysis (UA) positive for Candida species may predict 38-80% of systemic candidiasis.

• Blood culture is not helpful in diagnosing disseminated disease.

• Debate among authorities exists regarding the specificity and sensitivity of antigen- and antibody-specific tests.

• Urinary tract candidiasis: UA is a good test for detection of UTI caused by Candida species.

Imaging Studies:

• Imaging studies are not needed for routine cutaneous and vaginal candidiasis.

• X-ray evaluations for systemic candidiasis are often nonspecific; thus, differentiation of candidiasis from other disease processes may be difficult.

• Chest x-ray (CXR) may be helpful in diagnosis of pulmonary candidiasis.

• Disease spreads via the airway system; CXRs are characterized by bilateral, diffuse, and poorly marginated areas; pulmonary parenchymal densities are common.

• Other nonspecific findings include air bronchograms and obscure cardiac and hemidiaphragm borders.

• Infection spread via the blood system will produce a miliary nodular pattern.

• Esophagography with contrast is indicated for diagnosis of esophagitis caused by Candida species.

• Peristaltic abnormalities caused by small plaques appear as superficial filling defects. A nodular or cobblestone pattern may be seen.

• Findings may be similar to those seen with esophagitis caused by cytomegalovirus (CMV) or herpes simplex virus (HSV).

• Strictures may be seen with severe esophageal candidiasis.

• Ultrasound is useful for diagnosis of microabscesses in the liver, spleen, or kidneys.

• "Wheel within a wheel" hypoechoic zones surrounded by hyperechoic zones are early findings.

• Typical bull’s-eye lesion may evolve from the initial lesion.

• A uniformly hyperechoic lesion may be observed.

• Echogenic foci with variable degrees of acoustic shadowing are late findings.

• CT scan also allows diagnosis of microabscesses in the liver, spleen, or kidneys. Enhanced CT scan demonstrates microabscesses as low-attenuation foci in the liver and spleen.

• Intravenous pyelography (IVP) is indicated for diagnosis of urinary tract candidiasis

• Swollen kidneys from multiple microabscesses, deformity of renal outline, diminished renal excretion, papillary necrosis, and candidal fungal balls in the bladder or collecting system may be seen.

• Hydronephrosis is a common late finding.

• CT scan/MRI is indicated for diagnosis of CNS lesions.

Procedures:

• Endoscopy and biopsy

• Endoscopy provides direct visualization of small, white, mucosal plaques, which indicate esophageal candidiasis.

• Biopsies may be obtained for a more definitive diagnosis.

TREATMENT

Section 6 of 12

Emergency Department Care:

• Certain forms of candidiasis, such as superficial candidiasis, can be identified easily and treated with antifungal agents in the ED. Systemic infections are not seen frequently in the ED because patients usually are hospitalized for treatment of the underlying condition.

• Patients presenting to the ED with any form of candidiasis that requires more than a simple oral treatment regimen should be admitted for treatment of fungal infection as well as for the underlying condition.

• If the source of candidiasis is an indwelling catheter, the catheter should be removed immediately and replaced, and the tip sent for culture.

Consultations: Consultation may be necessary because candidiasis affects many organ systems. Specialists, including neurologists, gastroenterologists, and pulmonologists, should be called in to evaluate atypical findings.

MEDICATION

Section 7 of 12

Antifungal therapy should be started immediately after necessary cultures have been obtained from all suspected sites of infection.

Drug Category: Antifungals -- Amphotericin B, fluconazole, ketoconazole, and nystatin are the drugs most commonly used to treat candidiasis. When systemic agents are administered, monitor patients for side effects and complications common to the drug.

Drug Name	Fluconazole (Diflucan) -- Synthetic, broad-spectrum, bistriazole, oral antifungal agent that is highly selective inhibitor of fungal cytochrome P-450 and sterol C-14 alpha-demethylation. Commonly used in the treatment of vaginitis, oral thrush, cystitis, and bloodstream infections with or without venous catheter. Used to treat oropharyngeal, esophageal, and vaginal infections in patients with AIDS.
Adult Dose	Vaginitis: 150 mg PO once Oropharynx (thrush, not AIDS): 200 mg PO once or 100 mg/d x 5 d AIDS (oropharyngeal, esophageal, vaginal infection): 200 mg PO on day 1, followed by 100 mg qd until improvement seen (3-4 d); continued suppression dosing regimen is 100 mg PO qwk; if no response in 1 wk, change to amphotericin B (0.3 mg/kg IV qd x 7 d) Cystitis: 200 mg PO on day 1, followed by 100 mg qd x 4 d Bloodstream infections with or without venous catheter: 400 mg IV qd x 7 d, followed by 400 mg PO qd for 14 d after the last positive blood culture
Pediatric Dose	<3 years: Not recommended >3 years (see below) Vaginitis: 6 mg/kg Oropharynx (thrush, not AIDS): 3 mg/kg/d PO/IV as single dose AIDS (oropharyngeal, esophageal, vaginal infections): Not recommended Cystitis: Not recommended Bloodstream infections with or without venous catheter, alternative therapy: 6-12 mg/kg/d PO/IV for 28 d
Contraindications	Documented hypersensitivity
Interactions	Levels may increase with hydrochlorothiazides; levels may decrease with long-term use of rifampin; may decrease phenytoin concentrations; may increase concentrations of theophylline, tolbutamide, cyclosporine, glyburide, and glipizide; may increase effects of anticoagulants
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor closely if rashes develop and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) in patients with underlying medical conditions such as AIDS or malignancy and while taking multiple concomitant medications; not recommended for nursing mothers Convenience and efficacy of single-dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with oral fluconazole vs intravaginal agents

Drug Name	Econazole (Spectazole) -- Effective in cutaneous infections. Interferes with RNA and protein synthesis, as well as metabolism. In addition, disrupts fungal cell-wall membrane permeability, causing cell death.
Adult Dose	Apply topically tid/qid x 7-14 d
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	If sensitivity or irritation develops, discontinue use; for external use only; avoid contact with eyes

Drug Name	Ketoconazole (Nizoral) -- Imidazole broad-spectrum antifungal agent. Nizoral impairs synthesis of ergosterol (the main sterol of fungal cell membranes), allowing increased permeability and leakage of cellular components, causing cell death. Used in treatment of chronic mucocutaneous candidiasis and cutaneous infections.
Adult Dose	Mucocutaneous infections: 400 mg PO qd (with food) x 3-9 mo Cutaneous infections: Apply topically qd x 14 d
Pediatric Dose	Mucocutaneous infections <2 years: Not recommended >2 years: 5 mg/kg/d PO once; not to exceed 800 mg qd
Contraindications	Documented hypersensitivity, fungal meningitis
Interactions	Isoniazid may decrease bioavailability; coadministration of rifampin may decrease effects of either; may increase effect of anticoagulants; may increase toxicity of corticosteroids and cyclosporine (cyclosporine dosage can be adjusted); may decrease theophylline levels
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 ketoconazole

Drug Name	Miconazole (Desenex, Monistat, Micatin) -- Inhibits biosynthesis of ergosterol, damaging fungal cell wall membrane, which results in fungal cell death. Lotion preferred in intertriginous areas; cream must be applied sparingly to avoid maceration effects. Effective in treating vaginitis and cutaneous infections.
Adult Dose	Vaginitis: 200 mg vaginal tab (1 qd x 3 d) or 2% cream (5 g) qd hs for 7 d Cutaneous infections: Apply topically tid/qid x 7-14 d
Pediatric Dose	<12 years: Not recommended >12 years: 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

Drug Name	Nystatin (Mycostatin) -- Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei; effective against various yeasts and yeastlike fungi. Changes permeability of fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak. Treatment should continue until 48 h after disappearance of symptoms. Used for treatment of oral thrush (although not in AIDS patients) and cutaneous infections.
Adult Dose	Thrush: 200,000 U lozenge qid, or 500,000 U swish and swallow qid, or 2 500,000 U tabs tid x 14 d Cutaneous infections: Apply topically tid/qid x 7-14 d
Pediatric Dose	Administer as in adults (Not recommended for children unable to understand dosing instructions)
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Do not use to treat systemic mycoses

Drug Name	Clotrimazole (Mycelex, Lotrimin, Femizole-7) -- Broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells. Reevaluate diagnosis if no clinical improvement after 4 wk. Relief of pruritus usually within first week of treatment. If patient without clinical improvement after 4 wk, reevaluate diagnosis. Used in treatment of vaginitis.
Adult Dose	10 mg PO 5 times/d for 14 d; 100 mg vaginal tab, 2 qd hs x 3 d; 1% cream (5 g) qd hs x 7 d, gently massage into affected and surrounding skin areas bid for next 2-6 wk
Pediatric Dose	<3 years: Not established >3 years: 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	Amphotericin B (AmBisome) -- Polyene antibiotic produced by strain of Streptomyces nodosus. Agent can be fungistatic or fungicidal depending on concentration attained in body fluids and on susceptibility of fungus. Exerts effect by changing membrane permeability by binding to sterols, such as ergosterol, in fungal cell-wall membrane. Causes variety of intracellular components to leak, resulting in fungal cell death. Used in treatment of bloodstream infections, with or without venous catheter or with pulmonary or disseminated disease, and endocarditis. Can be used in combination with fluconazole to treat patients receiving peritoneal and chronic ambulatory peritoneal dialysis (CAPD).
Adult Dose	Bloodstream infections, with or without venous catheter: 0.5-0.6 mg/kg IV qd, for total dose of 5-7 mg/kg Bloodstream infections with pulmonary or disseminated disease: 0.6 mg/kg/d IV for 7 d, followed by 0.8 mg/kg IV qid until definitive evidence of resolution (most patients should receive 0.5-1 g total dose) Endocarditis: 0.6 mg/kg/d IV for 7 d, then 0.8 mg/kg IV qid; continue 6-10 wk after surgery Peritoneal and chronic ambulatory peritoneal dialysis: 4 mg/2 L bag IP for 24 h, then 3 mg/2 L bag IP qd in combination with fluconazole 150 mg IP q2d; add heparin 500 U/2 L bag; decrease exchange volume to 1-1.5 L, increase dwell time to 30 min; treat 4-6 wk
Pediatric Dose	<3 years: Not recommended >3 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Antineoplastic agents may enhance potential for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity increased with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Monitor renal function, serum electrolytes such as magnesium and potassium, liver functions, CBC, and hemoglobin; resume therapy at lowest level (eg, 0.25 mg/kg) if therapy interrupted for > 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion)

Drug Name	Micafungin (Mycamine) -- Member of new class of antifungal agents, echinocandins, that inhibit cell wall synthesis. Inhibits synthesis of 1,3-beta-D-glucan, an essential fungal cell wall component not present in mammalian cells. Indications include (1) prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation and (2) treatment of esophageal candidiasis.
Adult Dose	Candidiasis prophylaxis: 50 mg IV qd infused over 1 h Esophageal candidiasis: 150 mg IV qd infused over 1 h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Increases sirolimus and nifedipine AUC approximately 20%
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Common adverse effects may include headache, nausea, vomiting, and abdominal pain; other adverse effects include skin rash, delirium, phlebitis, shock, leukopenia, and hyperbilirubinemia; rare cases of elevated hepatic enzyme, BUN, and creatine levels have been reported; transient acute intravascular hemolysis and hemoglobinuria may occur; do not mix or infuse in same IV line with other medications because precipitate forms with other commonly used medications (flush existing IV line with 0.9% NaCl before and after infusion); protect from light following dilution

Drug Name	Caspofungin (Cancidas) -- Used to treat refractory invasive aspergillosis. 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	Not established
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 preexisting renal dysfunction or myelosuppression

Drug Name	Anidulafungin (Eraxis) -- Antifungal agent of the echinocandin class. Inhibits synthesis of 1,3-beta-D-glucan, an essential component of fungal cell walls. Indicated to treat esophageal candidiasis, candidemia, and other forms of candidal infections (eg, intra-abdominal abscesses, peritonitis).
Adult Dose	Candidemia or other candidal infections: 200 mg IV on day 1, decrease dose on day 2 and thereafter to 100 mg/d IV Esophageal candidiasis: 100 mg IV on day 1, decrease dose on day 2 and thereafter to 50 mg/d IV Do not exceed infusion rate of 1.1 mg/min
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Common adverse effects include hypokalemia, diarrhea, elevated hepatic enzyme levels, and headache; rare reports of serious hepatotoxicity; infusion-related reactions (eg, rash, urticaria, flushing, pruritus, dyspnea, hypotension) may occur, particularly with rapid infusion; following reconstitution, dilute further with D5W or NS before administration

Drug Name	Flucytosine (Ancobon) -- Converted to fluorouracil after penetrating fungal cells and inhibits RNA and protein synthesis. Active against Candida and Cryptococcus species and generally used in combination with amphotericin B for treatment of endocarditis. Can be used in combination with fluconazole to treat patients receiving peritoneal and chronic ambulatory peritoneal dialysis.
Adult Dose	100-150 mg/kg/d PO divided qid Peritoneal and chronic ambulatory peritoneal dialysis: 2 g IP loading dose, followed by 1 g PO qd; combine with fluconazole 150 mg IP q2d; add heparin 500 U/2 L bag; decrease exchange volume to 1-1.5 L, increase dwell time to 30 min; treat 4-6 wk
Pediatric Dose	Not established; suggested dose is similar to that used in adults
Contraindications	Documented hypersensitivity
Interactions	Amphotericin B may increase toxicity; cytosine may inactivate
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in bone marrow suppression; adjust dose in renal impairment

Drug Name	Posaconazole (Noxafil) -- Triazole antifungal agent. Blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. Available as oral susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.
Adult 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

FOLLOW-UP

Section 8 of 12

Further Outpatient Care:

• Uncomplicated vaginal and cutaneous candidiasis

• When treated in the ED and discharged with medication, patients should be instructed to see their primary physician if symptoms persist or worsen.

• For recurrent vulvovaginitis, patients should be screened for HIV infection, diabetes mellitus, leukemia, or other reasons why they may be immunocompromised.

• Severe candidiasis: If an underlying disorder is suspected, patients should be referred for workup in an outpatient setting for possible primary causes leading to the immunocompromised state.

In/Out Patient Meds:

• Most medications can be prescribed in an oral or topical form; thus, many infections can be treated on an outpatient basis with appropriate follow-up.

Transfer:

• Patients should be transferred to the specialty that cares for their most serious infection (eg, endophthalmitis should be treated by either ophthalmology or infectious disease).

• Patients with serious systemic candidiasis should be transferred to the critical care unit.

Complications:

• Candidiasis can spread from a local infection to one affecting almost any organ system. Prompt treatment should be instituted to decrease the chance of a systemic and possibly fatal complication.

• Complications include myocarditis, endophthalmitis, hepatosplenic abscess, and occasionally death.

• Candidiasis may be associated with chronic fatigue syndrome.

Prognosis:

• Prognosis for candidiasis is dependent on the particular site of infection and underlying illness.

• Superficial candidiasis (eg, vulvovaginitis, diaper rash) has an excellent prognosis with proper therapy and follow-up care.

• Systemic illnesses have a poorer prognosis, aggravated by the disease process commonly underlying such infections.

• Systemic candidiasis has a mortality rate as high as 77% depending on the underlying illness leading to compromised immune status.

Patient Education:

• Patients should be informed that immunocompromising agents and widespread administration of antibiotics may increase the likelihood of developing candidal infections.

• Patients should be educated to follow diets low in refined sugars and to avoid clothing that is tight and/or synthetic. Cotton underclothing may be beneficial.

• 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), Understanding Vaginal Yeast Infection Medications, Yeast Infection Diaper Rash, and Yeast Infection Skin Rash.

MISCELLANEOUS

Section 9 of 12

Medical/Legal Pitfalls:

• Remember that Candida species can affect many different organ systems. The clinician must be sure to identify any manifestation of candidal infection.

• The clinician must identify the primary disease process leading to an immunocompromised state.

TEST QUESTIONS

Section 10 of 12

CME Question 1: A 20-year-old woman presents to the ED with vaginal itching. The physician prepares a slide with vaginal secretions and KOH. What is most likely to be seen?

A: Narrow-based budding yeast
B: Pseudohyphae
C: Broad-based budding yeast
D: Spherules with endospores
E: Branched septate hyphae

The correct answer is B: Visualization of pseudohyphae under wet mount with or without KOH is pathognomonic for vaginal candidiasis.

CME Question 2: Which of the following is the earliest ultrasound finding in hepatic candidiasis?

A: Uniformly hyperechoic lesions
B: Bull's-eye lesions
C: Wheel-within-a-wheel lesions
D: Uniformly hypoechoic lesions
E: Echogenic foci with variable degrees of acoustic shadowing

The correct answer is C: The wheel-within-a-wheel lesion is an early ultrasound finding in hepatic candidiasis. Infection in the liver progresses to bull`s-eye lesions followed by uniformly hyperechoic lesions. Echogenic foci are an occasional finding on ultrasound in late stages of disease.

Pearl Question 1 (T/F): A 27-year-old white woman with no significant past medical history presents with recurrent vaginal yeast infections. Further workup is indicated.

The correct answer is True: Chronic vaginal candidiasis is often the first symptom of an underlying disorder of the immune system. HIV status should be discussed immediately with this patient. If status is unknown, an HIV test should be ordered. Less likely underlying disorders include diabetes mellitus and leukemia.

Pearl Question 2 (T/F): A 13-year-old boy with a history of leukemia presents with polyuria and dysuria. A urine culture is obtained and Candida albicans is identified. Further workup is indicated.

The correct answer is True: The patient should be immediately started on fluconazole, and an intravenous pyelogram should be performed to rule out renal candidiasis. Finally, the patient should be tested immediately for disseminated candidiasis, as urine cultures positive for Candida species predict systemic candidiasis up to 80% of the time.

Pearl Question 3 (T/F): Chest x-ray is important in diagnosing pulmonary candidiasis.

The correct answer is False: Chest x-rays are very nonspecific in differentiating candidiasis from other types of disease processes.

Pearl Question 4 (T/F): An 84-year-old Asian man presents with his third case of oral thrush in less than 2 years. He has no other significant past medical history or complaints today. Further workup is required.

The correct answer is False: The incidence of oral thrush caused by Candida species increases with age; it is fairly common in the elderly.

PICTURES

Section 11 of 12

Caption: Picture 1. Candidiasis. (Image courtesy of Hon Pak, MD)
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Caption: Picture 2. Candidiasis. A moist, erosive, pruritic patch of the perianal skin and perineum (with satellite pustule formation) is demonstrated in this woman with extensive candidosis. (Images courtesy of Matthew C Lambiase, DO)
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Caption: Picture 3. Candidiasis. Discrete superficial pustules developed within hours of birth on the hand of an otherwise healthy newborn. A potassium hydroxide preparation revealed spores and pseudomycelium, and culture demonstrated the presence of Candida albicans. (Images courtesy of Matthew C Lambiase, DO)
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Caption: Picture 4. Candidiasis. Dry, red, superficially scaly, pruritic macules and patches on the penis represent candidal balanitis. (Images courtesy of Matthew C Lambiase, DO)
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Caption: Picture 5. Candidiasis. White plaques are present on the buccal mucosa and the undersurface of the tongue and represent thrush. When wiped off, the plaques leave red erosive areas. (Images courtesy of Matthew C Lambiase, DO)
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Caption: Picture 6. Candidiasis. Erythema, maceration, and satellite pustules in the axilla, accompanied by soreness and pruritus result in a form of intertrigo. (Images courtesy of Matthew C Lambiase, DO)
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Caption: Picture 7. Candidiasis. A nailfold with candidal infection becomes erythematous, swollen, and tender with an occasional discharge. (Images courtesy of Matthew C Lambiase, DO)
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Caption: Picture 8. Candidiasis. Soreness and cracks at the lateral angles of the mouth (angular cheilitis) is a frequent expression of candidosis in elderly individuals. (Images courtesy of Matthew C Lambiase, DO)
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Caption: Picture 9. Candidiasis. Fine superficial pustules on an erythematous patchy base are suggestive of candidosis. (Images courtesy of Matthew C Lambiase, DO)
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Caption: Picture 10. Candidiasis. Candida infection should be in the differential diagnosis when one or more nails become discolored, has subungual discoloration, nailplate separation from the nailbed, and lack evidence of a dermatophyte. (Images courtesy of Matthew C Lambiase, DO)
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BIBLIOGRAPHY

Section 12 of 12

• Bodey GP: Candidiasis Pathogenesis: Diagnosis and Treatment. 1993.
• Hay DM: Yeast infections. Dermatol Clin 1996; 14(1): 113-123.
• Isselbacher KJ, Braunwald E, Wilson JD: Harrison's Principles of Internal Medicine. 1994:860-861.
• May HL, Aghababian RV, Fleisher GR: Emergency Medicine. 2nd ed. 1992:1204.
• Mora-Duarte J, Betts R, Rotstein C, et al: Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002 Dec 19; 347(25): 2020-9[Medline].
• Onion DK: The Little Black Book of Primary Care. 1996:125-126, 433-434.
• Rex JH, Bennett JE, Sugar AM, et al: A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute. N Engl J Med 1994 Nov 17; 331(20): 1325-30[Medline].
• Sanford JP, Gilbert DN, Moellering RC, Jr: The Sanford Guide to Antimicrobial Therapy. 1997.
• Sobel JD: Vulvovaginal candidiasis--what we do and do not know. Ann Intern Med 1984 Sep; 101(3): 390-2[Medline].
• Stine RJ, Chudnofsky CR: A Practical Approach to Emergency Medicine. 1994:793-794, 857-858.

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