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Author: Emily A Carpenter Rose, MD, Staff Physician, Department of Emergency Medicine, Los Angeles County/University of Southern California

Emily A Carpenter Rose is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Women's Association, and Christian Medical & Dental Society

Coauthor(s): 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

Editors: David FM Brown, MD, Assistant Professor, Department of Medicine, Department of Emergency Medicine, Division of Emergency Medicine, Harvard Medical School; Vice-Chair, 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; Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School

Author and Editor Disclosure

Synonyms and related keywords: candidiasis, Candida albicans, C albicans, Candida tropicalis, C tropicalis, Candida parapsilosis, C parapsilosis, Candida guilliermondi, C guilliermondi, Candida lusitaniae, C lusitaniae, Candida krusei, C krusei, Torulopsis glabrata, Tglabrata, mycotic infection, vaginitis, vulvar rash, oral thrush, conjunctivitis, endophthalmitis, diaper rash, infections of nail, infections of rectum, infections of skin folds, systemic candidiasis, oral candidiasis, gastrointestinal candidiasis, red macerated intertriginous areas, vulvovaginitis, candidal infection, nosocomial bloodstream infection, candidemia, fungemia, vulvovaginal candidiasis, candidal esophagitis

Background

The Candida fungus is both normal flora and an invasive pathogen. The range of infection with Candida species varies from a benign local mucosal membrane infection to disseminated disease. Severe disease is typically associated with an immunocompromised state including those vulnerable to iatrogenic pathogens in the intensive care unit or those with predisposing immunologic conditions such as malignancy, organ dysfunction, or immunosuppressive therapy.

Pathophysiology

Candida is a unicellular yeast whose cells reproduce by budding. This organism can flourish in most environments. It frequently colonizes the oropharynx, skin, mucous membranes, lower respiratory, and gastrointestinal and genitourinary tracts. Pathogenesis occurs with increased fungal burden and colonization, such as in the setting of broad-spectrum antimicrobial agents; breakdown of normal mucosal and skin barriers, which can occur with indwelling intravascular devices, recent surgery/trauma or tissue damage secondary to chemotherapy or radiation; or immune dysfunction secondary to disease states or iatrogenic conditions.
 
Disease manifestation of candidal infection can vary with type of host immunodeficiency. Lymphocytes and cell-mediated immunity are important in the prevention of mucosal candidiasis. Therefore, patients with T-cell deficiency, such as human immunodeficiency virus (HIV), have a propensity to develop recurrent and/or persistent mucocutaneous candidiasis. Patients with neutropenia are at risk for invasive candidiasis and candidemia as functioning monocytes and polymorphonuclear cells are responsible for killing pseudohyphae and blastospores. Complement and immunoglobulins are necessary for intracellular killing of the organisms and patients with deficiencies can have a more prolonged and complicated course of candidal infection.

Frequency

United States

  • Three quarters of women experience vaginitis in their lifetime, and 30% of vaginitis is caused by Candida. Vaginitis accounts for 10 million office visits per year.
  • Candida is the fourth most common cause of nosocomial bloodstream infection in the United States.
  • Invasive candidiasis is the most common invasive fungal infection in the United States. There is an increasing shift toward infections caused by non-albicans Candida species with 40-60% of the species currently being reported as non-albicans species.

International

  • Internationally, Candida epidemiology is similar to that of the United States.
  • Non-albicans Candida accounted for 70% of candidemia in a Northern Indian pediatric intensive care unit. Candida species isolated were Candida tropicalis (48.4%), C albicans (29.7%), C guilliermondii (14.1%), C krusei (6.3%), and C glabrata (1.6%).
  • Fungal keratitis is more prevalent in the tropics; therefore, Candida accounts for proportionately more fungal corneal isolates at temperate latitudes.

Mortality/Morbidity

  • Invasive candidiasis has a mortality rate of 40-50%, with an estimated cost of $40,000 per episode.
  • Neonates and children have better outcomes with approximately 20% mortality rate for candidemia.
  • Risk factors for death or poor prognosis are age, failure to remove central lines, malnutrition, and non-albicans fungemia.

Race

  • No racial predilection exists for infection with Candida.

Sex

  • Three quarters of all women experience at least one episode of vulvovaginal candidiasis in their lifetime, and about one half of these women experience a recurrence.

Age

  • Elderly persons with high Acute Physiology and Chronic Health Evaluation (APACHE) II scores as well as neonates with low gestational age, low APGAR scores, and congenital malformations are at high risk for candidal infection.



History

Candidal infection has a wide range of clinical manifestations from self-limited local mucocutaneous disease to severe sepsis with multiorgan system failure.
 
Local mucous membrane infections

Oral candidiasis, also referred to as thrush, is characterized by creamy white, curd-like patches on the tongue and oral mucosa. These patches are a pseudomembrane of Candida, desquamated epithelial cells, leukocytes, bacteria, keratin, necrotic tissue, and food debris. Chronic atrophic candidiasis, or denture sore mouth, is a chronic inflammatory reaction with epithelial thinning under dental plates. Candidal leukoplakia is firm, white plaques affecting the cheeks, lips, and tongue, which frequently have a protracted course and can be precancerous. Angular cheilitis is characterized as erythema and fissuring at the corners of the mouth. Risk factors for oral infection include antibiotic use, immunodeficiency, xerostomia, inhaled corticosteroids, and denture use. Symptoms include dry mouth, loss of taste, and occasionally, pain with eating.
 
Candida esophagitis is most commonly associated with treatment of hematopoietic or lymphatic malignancies. It is also an AIDS-defining illness, though patients with Candida esophagitis and no underlying illness have been reported. Symptoms include dysphagia, sensation of obstruction on swallowing, retrosternal chest pain, nausea, and vomiting. Definitive diagnosis is made by endoscopic biopsy. On endoscopy, white plaques similar to thrush may be present; ulcerations, pseudomembrane formation, and diverticula may also be seen. Candidal esophagitis can occur concomitantly with herpes simplex and cytomegalovirus infection in severely immunocompromised patients.
 
Other locations of the gastrointestinal tract are often infected with Candida. Lesions may be found in the stomach and small and large intestines most commonly in patients with neoplastic disease.
 
Candidal vaginitis is the most common form of mucosal candidiasis. Vulvovaginal candidiasis is usually secondary to overgrowth of normal flora Candida species in the vagina. Bacteria such as Lactobacillus acidophilus balance Candida and prevent yeast overgrowth and pathogenic infection. Conditions that disrupt the balance of normal vaginal flora include antibiotic use, oral contraceptives, contraceptive devices, high estrogen levels, and immunocompromised states such as diabetes mellitus and HIV. Of vulvovaginal candidiasis cases, 70-90% are caused by Candida albicans, while the remainder of infections are caused by C glabrata and C tropicalis. Symptoms classically are described as pruritus, vaginal irritation, and dysuria. Thick, curd-like discharge is often present, but scant discharge may also characterize infection. Vaginal edema and erythema are present on examination.
 
Epidemiologically, vaginal Candida infections are important as they may increase viral shedding in HIV-infected women.
 
Cutaneous candidiasis syndromes include the following: 

  • Generalized cutaneous candidiasis: This infection is characterized by widespread eruptions with increased severity in the genitocrural folds, anal region, axillae, and hands and feet that occurs in both children and adults.
  • Erosio interdigitalis blastomycetica: This is an intertriginous infection, which is predisposed to maceration.
  • Candida folliculitis: This is most frequently seen in immunocompromised hosts and among intravenous drug users.
  • Candida balanitis: This infection is usually acquired with sexual intercourse with an infected partner. Rash typically begins as vesicles on the penis that develop into patches similar in appearance to thrush. Extension may occur to the scrotum and buttocks. Symptoms include burning and pruritus.
  • Intertrigo: This develops in sites where skin surfaces are close in proximity. Lesions begin as vesicopustules that enlarge, rupture, and develop maceration and fissuring. Satellite lesions may be present. A variant form of cutaneous candidiasis in the intertriginous region has a miliary appearance.
  • Candidal paronychia: This is associated with frequent hand immersion in water and diabetes mellitus.
  • Diaper rash: Skin irritation is exacerbated by wet diapers.
  • Perianal candidiasis: Skin maceration and pruritus are frequent with frequent extension to the perineum.

Chronic mucocutaneous candidiasis is a term used to describe a heterogeneous group of Candida infections of the skin, mucous membranes, hair, and nails, which has a protracted course despite typical therapy. It is associated with T-cell lymphocyte dysfunction. A specific subset of patients with this phenomenon have autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy (APECED) syndrome with associated endocrine disorders.
 
Invasive candidal infections
 
Invasive candidiasis is a term used to describe severe and invasive disorders that include candidemia, disseminated candidiasis, deep organ involvement, endocarditis, endophthalmitis, and meningitis. Invasive infection is also described as the isolation of Candida from a normally sterile body site, including blood, peritoneal fluid, pleural fluid, intra-articular fluid, or cerebrospinal fluid.
 
Risk factors for invasive candidiasis include prolonged intensive care unit (ICU) stay (incidence peaks around day 10), presence of a central venous catheter, acute renal failure, treatment with broad-spectrum antibiotics, parenteral nutrition, high APACHE II scores, diabetes, immunosuppressive therapy, surgery (especially upper gastrointestinal tract), hemodialysis, pancreatitis, malignancy, transplantation, and organ dysfunction.
 
Skin manifestations of disseminated candidiasis include clusters of painless pustules on an erythematous base on any area of the body. These lesions may be macular or pustular or may have central necrosis.
 
Acute disseminated candidiasis, or hepatosplenic candidiasis, is most commonly seen in patients with hematologic malignancy who recently had an episode of neutropenia. Symptoms include fever, right upper quadrant pain, and tender hepatosplenomegaly. Multiple organs are frequently involved, and discrete persistent microabscesses occur in the liver, spleen, and kidneys. A palpable erythematous rash may be present indicating evidence of small vessel vasculitis. Presumed etiology is prior episode of candidemia, although invasion through portal vasculature has been theorized.
 
Central nervous system candidiasis usually occurs as a complication of hematogenously disseminated candidiasis. Candida typically forms multiple microabscesses and small macroabscesses scattered throughout the brain. Patients with Candida meningitis usually have meningeal irritation and CSF pleocytosis. Untreated, the mortality rate is high. Intraventricular drains increase risk of CNS candidal infection.
 
Candidal pneumonia occurs rarely as bronchopneumonia originating from endobronchial inoculation or more commonly a hematogenously seeded, nodular diffuse infiltrate. This presentation may be difficult to distinguish from congestive heart failure or Pneumocystis pneumonia. Diagnosis is also complicated by the inability to confirm that positive cultures are not oropharyngeal contaminant or colonization. Candida empyema cases have been documented.
 
Candida can infect both the pericardium and myocardium, and these infections are usually associated with disseminated disease. Candidal pericarditis is rare but fatal without treatment and has been known to cause tamponade. Infective endocarditis with Candida is usually seen in patients with a chronic indwelling intravenous catheter or large-caliber hemodialysis catheter. Other risk factors include congenital cardiac abnormalities, prosthetic valves, and intravenous illicit drug use. Fungal vegetations are often large and more frequently associated with embolic events. The mortality rate is approximately 45% with combined medical and surgical therapy.
 
Urethral candidiasis can occur in both men and women. In women, it is commonly secondary to an extension of Candida vaginitis. In men, it is usually secondary to sexual contact with women with vaginitis. Invasive infections of the bladder and kidneys can occur, though it is typically in immunocompromised patients and secondary to hematogenous spread.
 
Ocular candidiasis can occur in the form of endophthalmitis. Endophthalmitis may occur secondary to exogenous spread, such as trauma or surgery, or endogenous spread as a result of hematologic seeding.
 
Untreated candidemia has been associated with retinal lesions in up to 37% of patients. Candida ophthalmitis begins as a choroidal lesion that progresses to an area of retinal necrosis followed by vitreitis and endophthalmitis. Endophthalmitis is characterized by retinal infiltrates and vitreous abnormalities. Chorioretinal involvement appears as focal, white, infiltrative lesions on the retina. Vitreal haze is present with vitreous extension of the infection. Symptoms include pain and decreased visual acuity. Untreated, ophthalmitis will lead to blindness. Typically, involvement is unilateral, but bilateral cases have been reported. C albicans is the most frequent culprit.
 
Osseous or intra-articular infections may occur secondary to either hematogenous spread or exogenous inoculation during trauma or joint injection. Osteomyelitis occurs most commonly in vertebrae in adults and in long bones in children. Spinal infection can progress to a diskitis. Arthritis can be acute and suppurative, and the knee is most commonly affected. Diagnosis of osteoarticular infections may be delayed as symptoms are frequently more subtle than bacterial infections in the same location and patients often present several weeks to months after an episode of candidemia. Fever is typically absent.
 
Candidal peritonitis is most frequently secondary to peritoneal dialysis catheter seeding or gastrointestinal surgery.
 
Mediastinitis secondary to candidal infection may occur after thoracic surgery.
 
Neonatal invasive candidiasis occurs with an incidence inversely proportional to birth weight. Candida colonization is found in approximately 30% of infants weighing less than 1500 grams at birth weight. Sources of invasive infection in one study included blood (70%), urine (15%), cerebrospinal fluid (10%), and peritoneal fluid (5%). C albicans and C parapsilosis are the most common species found in neonates.

Candida amnionitis may occur after prolonged rupture of the membranes in mothers given parenteral antibiotics. A neonate’s skin may have pustules, vesicles, or diffuse erythema.

Physical

See History.

Causes

  • C albicans is the most common pathogenic species identified. Other species that are commonly found include C glabrata, C parapsilosis, C tropicalis, and C krusei.
  • Non-albicans species have been associated with specific patient populations. C glabrata is seen most commonly in patients with neoplastic disease; C tropicalis in patients with leukemia or neutropenia; C parapsilosis among neonates and those with an indwelling intravenous catheter; and C krusei in stem cell transplant recipients and in patients with leukemia who have received fluconazole prophylaxis.
  • Denture use, immunosuppressant, antibiotic therapy, and aging are risk factors for oral colonization with C glabrata. C glabrata exhibits lower oral keratinocyte-adherence capacity but higher denture surface adherence ability.



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

Mucocutaneous candidiasis - Contact or allergic dermatitis, folliculitis, Stevens-Johnson syndrome
GI tract candidiasis - Viral infection or gastroesophageal reflux disease (GERD)
Respiratory candidiasis - Bacterial or other fungal infection, acute respiratory distress syndrome (ARDS)
Genitourinary candidiasis - Bacterial infection, pyelonephritis
Candidemia - Bacteria sepsis or endocarditis
Disseminated candidiasis - Bacterial sepsis, meningitis, tuberculosis
Hepatosplenic candidiasis - Abscess, cholecystitis, ascending cholangitis, malignancy recurrence



Lab Studies

  • The criterion standard diagnostic tool for mucocutaneous candidiasis is culture. Cutaneous or mucosal scrapings can be used for a potassium hydroxide smear or Gram stain, which show hyphae, pseudohyphae, and budding yeast forms. The sensitivity of wet mount is as low as 39.6%.
  • Savyon Diagnostics currently is developing a rapid yeast detection kit for home diagnosis of vulvovaginal candidiasis. Preliminary data indicate better sensitivity than wet mount, and it costs less than culture.
  • Invasive Candida infections are typically difficult to diagnose because the clinical presentation is frequently similar to other disease states or bacterial infections, and cultures are unreliable. In one report, blood cultures were positive in only 50-70% of disseminated candidiasis cases when the disease was proven by autopsy. Thus, nonculture diagnostic techniques are frequently used to aid in diagnosis. The 1,3 beta-glucan assay, which measures the fungal cell was component, has a sensitivity of 70% and specificity of 87%.
  • Non–Food Drug Administration (FDA)–approved diagnostic tools include the Platellia Aspergillus ELISA (PA-ELISA) and polymerase chain reaction–based assay.
  • The peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) is used to distinguish C albicans from non-albicans Candida species.
  • CHROMagear is a specialized media for Candida isolation, which distinguishes C albicans, C tropicalis, and C krusei based on the species’ distinctive pigments.

Imaging Studies

  • Imaging studies are not necessary for routine mucocutaneous candidiasis.
  • Radiographic evaluations for systemic candidiasis are often nonspecific; thus, differentiation of candidiasis from other disease processes may be difficult.
  • Chest radiography may be helpful in making the diagnosis of pulmonary candidiasis.
    • Disease spreads via the airway system. Chest radiographic findings are characterized by bilateral, diffuse, and poorly marginated areas; pulmonary parenchymal densities are common.
    • Other nonspecific findings include air bronchogram and obscure cardiac and hemidiaphragm borders.
    • Hematogenous infection may 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).
    • Stricture may occur in severe esophageal candidiasis.
  • Ultrasonography 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 allows diagnosis of microabscesses, represented by low-attenuation foci, in the liver, spleen, or kidneys.
  • Intravenous pyelography (IVP) may be helpful in the diagnosis of urinary tract candidiasis.
    • Renal edema may be present 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 evaluation of CNS lesions and prior to lumbar puncture.

Procedures

Endoscopy, tissue biopsy, and percutaneous needle aspiration of a body site suspected of Candida infection are recommended to aid in diagnosis. Positive candidal cultures in a normally sterile site should not be disregarded as a contaminant.



Emergency Department Care

Mucocutaneous candidiasis is often encountered and treatment initiated in the emergency department. Systemic infections in patients with risk factors for Candida infection should be admitted to the hospital and cultures taken prior to initiating antimicrobial therapy

Other treatment of candidiasis

  • Mucocutaneous infection typically responds to topical therapy. Nystatin is the least expensive option for oral thrush, but patients frequently complain of its bitter taste. Clotrimazole troches are as effective and less bitter. Proper denture cleansing and care are important measures against oral candidiasis. 
  • Topical therapy is first line for esophageal candidiasis, but systemic therapy is typically required. 
  • Intertrigo and diaper rash respond to decreased moisture around the skin. Nystatin powder or cream is used with the addition of a topical steroid for diaper rash. 
  • Uncomplicated vulvovaginal candidiasis treatment includes many options of topical or oral therapy. Recurrent candidal vaginitis requires a prolonged course of oral medication.
  • Invasive candidiasis typically requires parenterally administered antifungal therapy.
  • Candida endocarditis frequently requires both medical and surgical therapy. Valve replacement and vegetation removal is often necessary. Antifungal therapy is typically continued for 6-10 weeks parenterally.
  • CNS candidal infection can often successfully be treated without intrathecal instillation.
  • Peritoneal candidal infection secondary to peritoneal dialysis may respond to peritoneal infusion of antifungal agents in dialysate fluid.
  • Candida keratitis may require corneal grafting if not responsive to treatment.
  • Full-term infants with Candida amnionitis typically respond to topical therapy. Premature infants frequently require systemic antifungal agents and have a poorer prognosis.
  • Endophthalmitis may require vitrectomy and direct intravitreal antifungal instillation.

Consultations

  • Infectious disease specialists are typically involved in cases of invasive candidiasis.
  • Gastroenterologists typically perform diagnostic endoscopy.
  • Surgical drainage may be required with organ involvement and abscess formation.
  • Orthopedic surgeons are involved in the management of osteomyelitis and intra-articular infections. 
  • Cardiothoracic surgeons are frequently necessary in the treatment of endocarditis.
  • Ophthalmologic consultation should be obtained on all patients with candidemia to exclude evidence of ocular involvement.



  • Antifungal therapy should be started immediately after necessary cultures have been obtained from all suspected sites of infection.
  • Significant advances have been made in the treatment of Candida with the development of newer azoles, echinocandins, and lipid formulations of amphotericin B.

Drug Category: Antifungals, azole

Azoles are fungicidal only at very high concentrations. Azoles function by selectively inhibiting the synthesis of an essential component of fungal cell membrane, ergosterol.

Drug NameFluconazole (Diflucan)
DescriptionSynthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Available as tablets for oral administration, as a powder for oral suspension, and as a sterile solution for IV use. Has fewer adverse effects and better tissue distribution than older systemic imidazoles.
Daily dose varies with indication.
Fluconazole penetrates the cerebrospinal fluid, kidneys, and liver well. It is concentrated and excreted by the kidneys in its active form so is effective against urinary tract infections.
Adult DoseOropharyngeal and esophageal disease: 100 mg/d PO/IV for 7-14 d
Candidemia and invasive candidiasis: 800-mg loading dose, followed by 400 mg/d PO/IV; if C glabrata, dose should be 800 mg/d
Renal insufficiency:
CrCl 25-49 mL/min: Decrease dose by 50%
CrCl <25 mL/min: Decrease dose by additional 75%
Hemodialysis: Usual daily dose after each dialysis
Bone marrow transplant: 200-400 mg/d PO/IV starting at time of bone marrow ablation and continuing until neutropenia resolves; recent studies seem to indicate continuing therapy for longer periods of time may decrease mortality in transplant recipients
Pediatric Dose4.5-6 mg/kg/d PO/IV; dosages of 10-12 mg/kg/d have been used
ContraindicationsDocumented hypersensitivity
InteractionsCYP450 2C19 and 3A4 inhibitor; levels may increase with hydrochlorothiazide; fluconazole levels may decrease with long-term coadministration of rifampin; may increase concentrations of theophylline, phenytoin, tolbutamide, cyclosporine, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsAdjust dose for renal insufficiency; closely monitor if rashes develop, and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) when taken with underlying medical conditions (eg, AIDS, malignancy) or while taking multiple concomitant medications; not recommended for breastfeeding mothers; QT prolongation and torsade de pointes can occur; rarely, anaphylactic reactions, Stevens-Johnson syndrome, and toxic necrolysis can occur
Convenience and efficacy of single-dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with oral fluconazole versus intravaginal agents

Drug NameItraconazole (Sporanox)
DescriptionHas fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes. Effective against broad range of fungi, including Candida species and is indicated for the treatment of cutaneous, oral, esophageal, and disseminated candidiasis.
Available in IV, 100-mg capsules, and oral solution at 10 mg/mL.
Capsules require gastric acidity for absorption and should be taken with food to increase absorption. Liquid formulation increases bioavailability and decreases need for acidity for proper absorption.
Use of solution has been recommended in mucosal and invasive candidiasis, while capsules can be used in onychomycosis and dermatophyte infections.
Adult DoseCutaneous candidiasis and onychomycosis: 200 mg PO bid for 7 d/mo for 3-6 mo
Oropharyngeal and esophageal candidiasis: 200 mg/d PO for 7-14 d
Candidemia and invasive candidiasis: 200 mg PO tid for 3 d, followed by 200 mg bid for 14-21 d
Pediatric DoseCutaneous candidiasis: 3-5 mg/kg/d PO for 30 d
ContraindicationsDocumented hypersensitivity
InteractionsAntacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin or simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death
Monitoring of liver enzymes recommended; potent inhibitor of CYP3A4 (may increase plasma concentrations of terfenadine, midazolam, cyclosporin, cisapride, quinidine, atorvastatin, simvastatin, lovastatin when coadministered); CYP3A4 inducers, such as phenytoin, rifampin, and isoniazid, may decrease itraconazole concentrations
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in hepatic insufficiency

Drug NameKetoconazole (Nizoral)
DescriptionImidazole 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 DoseMucocutaneous infections: 400 mg PO qd (with food) for 3-9 mo
Cutaneous infections: Apply topically qd for 14 d
Pediatric DoseMucocutaneous infections:
<2 years: Not recommended
>2 years: 5 mg/kg/d PO once; not to exceed 800 mg qd
ContraindicationsDocumented hypersensitivity; fungal meningitis
InteractionsIsoniazid 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
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsHepatotoxicity 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 NameMiconazole (Desenex, Monistat, Micatin)
DescriptionInhibits 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 DoseVaginitis: 200 mg vaginal tab (1 qd for 3 d) or 2% cream (5 g) qd hs for 7 d
Cutaneous infections: Apply topically tid/qid for 7-14 d
Pediatric Dose<12 years: Not recommended
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsIf sensitivity or chemical irritation occurs, discontinue use; use only externally; avoid contact with eyes

Drug NameVoriconazole (VFEND)
DescriptionAvailable in oral and parenteral forms. FDA approved for esophageal candidiasis and candidemia. Used clinically for serious candidal infections refractory to amphotericin B. Voriconazole has been found to be active against C glabrata and C krusei as well as isolates that have developed resistance to fluconazole.
Adult DoseLoading dose: 6 mg/kg IV q12h infused over 2 h for 2 doses
Maintenance: 4 mg/kg IV q12h infused over 2 h, when able to tolerate PO may switch to 200 mg PO q12h
Note: For inadequate response, may increase to 300 mg PO q12h; <40 kg administer oral maintenance dose of 100 mg PO q12h (may increase to 150 mg PO q12h)
Pediatric DoseNot established
ContraindicationsDocumented 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
InteractionsCYP450 2C19 (highest affinity), 2C9, and 3A4 (minor) substrate and inhibitor; CYP450 inducers (eg, rifampin) have shown to decrease steady-state peak plasma levels by up to 93%; may increase serum levels of drugs metabolized by CYP450 2C19 or 2C9, of which some are contraindicated (eg, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids), others may need more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG-CoA inhibitors, benzodiazepines, calcium channel blockers)
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsDecrease 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

Drug NamePosaconazole (Noxafil)
DescriptionTriazole 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 Dose200 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
ContraindicationsDocumented hypersensitivity; coadministration with ergot alkaloids; coadministration with CYP3A4 substrates likely to result in serious toxicities (eg, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine)
InteractionsMetabolized 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)
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCommon 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

Drug NameClotrimazole (Mycelex, Lotrimin, Mycelex Troches)
DescriptionNonabsorbable imidazole. Broad-spectrum synthetic antifungal agent that inhibits growth of yeasts and fungal growth by altering cell membrane permeability, which causes fungal cell death.
Therapy is directed at the underlying condition, with the goal of minimizing symptoms and preventing complications.
Adult DoseOPC: 10-mg troche to be dissolved in the mouth 5 times per d for 7 d
Cutaneous candidiasis: Apply 1% cream, lotion, or solution bid/tid
Vaginal candidiasis: 100-mg pessaries qd for 6 d; 1 applicatorful intravaginally of 1%, 2%, or 10% cream qhs
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsNot for treatment of systemic fungal infections; avoid contact with the eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy

Drug NameEconazole (Spectazole)
DescriptionAntifungal agent that is a water-miscible base consisting of pegoxol 7 stearate, peglicol 5 oleate, mineral oil, benzoic acid, butylated hydroxyanisole, and purified water. The color of the soft cream is white to off white, and it is for topical use only. Interferes with RNA and protein synthesis and metabolism. Disrupts fungal cell wall permeability, causing fungal cell death. Exhibits broad-spectrum antifungal activity against many gram-negative organisms. Effective in cutaneous infections.
Adult DoseApply sparingly over affected areas bid
Pediatric DoseApply as in adults
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsIf sensitivity or irritation develops, discontinue use; for external use only; avoid contact with eyes

Drug Category: Antifungals, polyenes

Polyenes (nystatin and amphotericin B) bind to ergosterol on the fungal cell membrane and create pores in the membrane resulting in leakage of intracellular proteins thereby destroying the fungal cell.

Drug NameAmphotericin B, conventional (Amphocin, Fungizone)
DescriptionProduced from a strain of Streptomyces nodosus. Antifungal activity of amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at sites containing ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large losses of ions and other molecules. A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity of amphotericin B may reside in ability to cause auto-oxidation of cell membranes.
In recent years, lipid formulations have been developed. Total dose needs to be adjusted depending on type of candidal infection being treated. Most patients receive a total dose of 0.5-1.5 g.
Adult Dose0.3-1.5 mg/kg/d IV infused in 5% dextrose over 2-4 h; 10-mg lozenges or 1 mL of a 100-mg/mL sol PO qid
Candiduria: Continuous bladder irrigation at concentrations of 50 mg/L for 3 consecutive days
Pediatric DoseAdminister as in adults; typically better tolerated in neonates than in adults and has improved CSF penetration
ContraindicationsDocumented hypersensitivity
InteractionsAntineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cyclosporine
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsMonitor renal function, serum electrolytes such as magnesium and potassium, liver function, CBC, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients with neutropenia who are receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock; nephrotoxicity may occur and may be irreversible

Drug NameAmphotericin B, liposomal (AmBisome)
DescriptionNovel lipid formulations of amphotericin B that deliver higher concentrations of the drug, with a theoretical increase in therapeutic potential and decreased nephrotoxicity. Produced from a strain of S nodosus. Antifungal activity of amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at sites containing ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large losses of ions and other molecules. A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity of amphotericin B may reside in ability to cause auto-oxidation of cell membranes.
Formulation types include amphotericin B lipid complex (ABLC, Abelcet), amphotericin B colloidal dispersion (ABCD, Amphotec), and liposomal amphotericin B (L-AMB, AmBisome).
ABLC and ABCD approved for treating adults and children with fungal infections refractory to or intolerant of conventional amphotericin B. L-AMB is approved for aspergillosis, candidiasis, and cryptococcosis, and also for patients with neutropenia who have persistent fever on broad-spectrum antibiotics.
Adult DoseABLC: 5 mg/kg/d IV, duration of infusion 1-2 h
ABCD: 3-6 mg/kg/d IV, duration of infusion 1-2 h
L-AMB: 1-7 mg/kg/d IV, duration of infusion 1-2 h
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity
InteractionsAntineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the risk of renal toxicity is increased with cyclosporine
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsMonitor renal function, serum electrolytes such as magnesium and potassium, liver function, CBC, and hemoglobin concentrations; resume therapy at the lowest level (eg, 0.25 mg/kg) when therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients with neutropenia who are receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock

Drug NameNystatin (Mycostatin)
DescriptionFungicidal and fungistatic antibiotic obtained from Streptomyces noursei; effective against various yeasts and yeastlike fungi. Changes permeability of fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak.
Treatment should continue until 48 h after disappearance of symptoms. Used for treatment of oral thrush (although not in patients with AIDS) and cutaneous infections.
Adult DoseThrush: 200,000 U lozenge qid, or 500,000 U swish and swallow qid, or 2 500,000 U tabs tid for 14 d
Cutaneous infections: Apply topically tid/qid for 7-14 d
Pediatric Dose100,000 U (one mL) in each cheek qid for oral thrush in infants
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsNot for treatment of systemic mycoses; large oral doses may cause gastrointestinal distress; patients often complain of bitter taste

Drug Category: Antimetabolite

Flucytosine is given occasionally in combination with amphotericin B for central nervous system infections.

Drug NameFlucytosine (Ancobon)
DescriptionAlthough the exact mode of action is unknown, it is proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism where it is converted to 5-fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against Candida and Cryptococcus species and generally used in combination with amphotericin B.
Use in combination with another agent because acquired resistance develops frequently when flucytosine is administered alone.
Well absorbed orally but should be administered IV to critically ill patients.
Adult Dose100-150 mg/kg/d PO divided q6h
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity
InteractionsAmphotericin B may increase toxicity of flucytosine; cytosine may inactivate flucytosine
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in bone marrow suppression; adjust dose in renal impairment

Drug Category: Antifungals, echinocandins

Echinocandins have potent fungicidal activity against Candida species and have successfully treated Candida resistant to azoles. These drugs are not metabolized through the CYP450 system. They act by inhibiting the synthesis of an essential cell wall component that is not present in mammalian cells.

Drug NameMicafungin (Mycamine)
DescriptionMember 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 DoseCandidiasis prophylaxis: 50 mg IV qd infused over 1 h
Esophageal candidiasis: 150 mg IV qd infused over 1 h
Pediatric Dose4 mg/kg/d IV; neonate dosing may be larger than expected
ContraindicationsDocumented hypersensitivity
InteractionsIncreases sirolimus and nifedipine AUC approximately 20%
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCommon 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 NameCaspofungin (Cancidas)
DescriptionFDA approved to treat candidemia, invasive candidiasis, and esophageal candidiasis. A glucan synthesis inhibitor that inhibits synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall. Caspofungin has demonstrated activity against C albicans, C glabrata, C guilliermondii, C krusei, C parapsilosis, and C tropicalis. Activity against C parapsilosis may only be fungistatic. Response rate has been demonstrated to be 73% for caspofungin as compared to 62% for amphotericin B.
Adult Dose70 mg IV over 1 h on day 1; 50 mg IV qd thereafter
Pediatric DoseNot established; may use if patient refractory to standard therapy; 50 mg/m2/d IV suggested; other sources suggest 2 mg/kg/d IV (dosing based on surface area may be best)
ContraindicationsDocumented hypersensitivity
InteractionsCoadministration 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)
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in moderate hepatic dysfunction (ie, decrease dose to 35 mg/d); may exacerbate preexisting renal dysfunction or myelosuppression; adverse effects include gastrointestinal upset, skin reactions, rare anaphylaxis, and pulmonary infiltrates



Further Inpatient Care

  • Patients with invasive candidiasis often have a prolonged inpatient course and may require several weeks of parenteral antifungal therapy.
  • Removal of invasive catheters with positive fungal culture results is an essential step in management.

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 immunologic dysfunction. 
  • 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

  • Localized mucocutaneous infections are treated with outpatient topical and oral medication. Patients with invasive infections that have stabilized may be discharged with parenteral medications administered at home.

Transfer

  • Patients with invasive candidiasis may require transfer to a facility where intensive care and specialty consultations are available.

Deterrence/Prevention

  • Screening pregnant women for vaginal infection and subsequently treating the infection, including vaginal candidiasis, reduces preterm delivery rates by 50%.
  • Multiple studies have been performed evaluating fluconazole prophylaxis in the ICU; however, the studies had either limited numbers or were performed in only one center, thereby limiting the ability to apply the evidence to the general population.
  • Candida prevention in the neonatal intensive care unit is also controversial. Fluconazole prophylaxis can lead to the emergence of Candida species that are not susceptible to fluconazole. This is a concern as mortality varies substantially by Candida species. C glabrata is associated with the highest mortality rate in neonates. Studies have demonstrated that less frequent dosing may delay the emergence of antifungal resistance but more evidence-based data are required.

Complications

  • Untreated candidemia can lead to metastatic foci of virtually any organ system and may lead to blindness, organ failure, and death.

Prognosis

  • Prognosis varies based on location of infection. Local mucocutaneous infections typically respond well to medical therapy. Response to invasive infection is determined by how quickly infection with Candida is recognized and treatment is initiated as well as underlying host immune response and comorbidities.

Patient Education



Medical/Legal Pitfalls

  • Many physicians treating patients with invasive candidiasis are not aware of the risk and consequences of ocular candidiasis. A formal ophthalmologic examination is required in all patients with systemic disease.

Special Concerns

  • Invasive candidiasis requires clinical suspicion and is often difficult to diagnose. Missed infections have high morbidity and mortality. Physicians must consider Candida infection as a possible pathogen in patients with risk factors. Because cultures frequently do not grow Candida species in known patients with candidemia, positive blood cultures for Candida should never be regarded as a contaminant. Antifungal therapy must be considered in critically ill patients on broad-spectrum antibiotics, especially if they are known to be colonized with Candida species.



Media file 1:  Candidiasis. Image courtesy of Hon Pak, MD.
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Media file 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. Image courtesy of Matthew C Lambiase, DO.
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Media file 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. Image courtesy of Matthew C Lambiase, DO.
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Media file 4:  Candidiasis. Dry, red, superficially scaly, pruritic macules and patches on the penis represent candidal balanitis. Image courtesy of Matthew C Lambiase, DO.
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Media file 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. Image courtesy of Matthew C Lambiase, DO.
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Media file 6:  Candidiasis. Erythema, maceration, and satellite pustules in the axilla, accompanied by soreness and pruritus, result in a form of intertrigo. Image courtesy of Matthew C Lambiase, DO.
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Media file 7:  Candidiasis. A nailfold with candidal infection becomes erythematous, swollen, and tender with an occasional discharge. (Image courtesy of Matthew C Lambiase, DO.
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Media file 8:  Candidiasis. Soreness and cracks at the lateral angles of the mouth (angular cheilitis) is a frequent expression of candidosis in elderly individuals. Image courtesy of Matthew C Lambiase, DO.
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Media file 9:  Candidiasis. Fine superficial pustules on an erythematous patchy base are suggestive of candidosis. Image courtesy of Matthew C Lambiase, DO.
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Media file 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. Image courtesy of Matthew C Lambiase, DO.
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REFERENCES

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