Candidiasis

Candidiasis: Excerpt from The 5-Minute Pediatric Consult

Theoklis Zaoutis, MD

Candidiasis - BASICS

Candidiasis - description

A spectrum of diseases caused by Candida species (yeasts):

• In immunocompetent children, most candidiasis is manifested as superficial mucosal (oropharyngeal candidiasis or thrush) and cutaneous (diaper dermatitis) infection.
• In immunocompromised children, Candida may cause invasive and disseminated disease.

Candidiasis - general prevention

• Sterilize bottle nipples and toys to prevent reinoculation of oral candidiasis.
• Avoid unnecessarily long courses of broad-spectrum antibiotics.
• Maintain IV catheters and catheter–skin insertion sites appropriately.

Candidiasis - epidemiology

Although C. albicans was once the dominant species in invasive candidiasis, non-albicans Candida species are rapidly emerging as significant pathogens.

Candidiasis - incidence

• The incidence of nosocomial Candida infections has risen over the past 20 years, and Candida spp. are currently the 4th most common recovered isolates in cases of nosocomial bloodstream infection.
• The increase in invasive candidal infections is likely a result of advances in medical therapy that have increased the number of susceptible hosts.

Candidiasis - risk factors

Surgery, central venous catheters, neonates, total parenteral nutrition, transplant recipients, malignancy, neutropenia, and burn patients

Candidiasis - pathophysiology

• Colonizes the mouth, GI tract, respiratory tract, and vagina. Colonization occurs within the first month of life; acquired from the mother by vertical transmission
• Candidiasis occurs when changes in host defense (locally or systemically) allow for overgrowth of the organism.
• In the immunocompromised host, systemic infection results from hematogenous spread after local invasion.

Candidiasis - etiology

• Neonatal infection is acquired from infected vaginal mucosa during birth. Transmission also occurs during nursing from the mother’s breast or from imperfect sterilization of bottle nipples.
• 80% of vaginal candidiases are caused by C. albicans; the remainder are caused by other Candida species, including C. glabrata and C. tropicalis.

Candidiasis - associated conditions

Candida spp. may cause disease at any site.

• Mucosal candidiasis:
  • Oropharyngeal candidiasis (thrush) occurs in up to 40% of healthy newborns. Patches of white, curdish material are visible on the buccal and gingival mucosa. It may cause mouth pain and poor nursing. In older children, it is associated with the use of antibiotics or immunosuppressive drugs, conditions of endocrine or immune dysfunction, and malignancy.
  • Candidal glossitis occurs secondarily to antibiotic therapy. The tongue is smooth and erythematous, and patients complain of glossodynia (painful tongue). Perlèche (angular cheilosis) results from chronic licking of the corners of the mouth and is characterized by fissuring, erythema, and pain.
  • Esophageal candidiasis occurs in HIV-infected patients and those on immunosuppressive therapy; 30% have associated thrush.
• Cutaneous candidiasis:
  • Diaper dermatitis is most common during infancy because of predisposing factors found with diaper use.
  • Intertriginous candidiasis is characterized by a confluent, erythematous, weeping rash with a scaling edge found at skin folds: Axillae, groin, gluteal folds, intramammary region, interdigital spaces, and umbilicus. Predisposing factors in healthy patients include chronic moisture, recent antibiotic use, and obesity.
• Vaginal candidiasis: Characterized by vaginal discharge (curdlike or mucoid), pruritus, vulvar burning, and dysuria. Oral contraceptives, antibiotics, pregnancy, corticosteroids, and immunodeficiency are predisposing conditions. Classified as uncomplicated or complicated:
  • Uncomplicated: 90% of patients; condition is mild to moderate; frequency is sporadic; organism is C. albicans; the host is immunocompetent.
  • Complicated: 10% of patients; presence of any one of the following factors defines a complicated infection: Severe, recurrent infection by non-albicans Candida species; or predisposing host factor
  • The reliability of self-diagnosis is poor (<50% correct); therefore, potassium hydroxide (KOH)/pH testing is suggested for diagnosis.
• Congenital candidiasis: Cutaneous infection acquired from contaminated amniotic fluid that is usually treated with topical antifungal agents and has an excellent prognosis
• Invasive candidiasis:
  • Defined as candidemia and disseminated candidiasis
  • Occurs in the immunocompromised host. Risk factors include prematurity, malignancy, immunodeficiency syndromes, diabetes mellitus, broad-spectrum antibiotic therapy, corticosteroids, chemotherapy, hyperalimentation, indwelling catheters, recent complex surgery, and organ transplantation.
  • The most frequent sites of involvement are the GI tract, lungs, kidneys, liver, spleen, eyes, and brain. Fungal sepsis may occur. Peritoneal, urinary tract, and cardiac valve candidal infections are most often related to instrumentation or catheterization in the immunocompromised host.
• Chronic mucocutaneous candidiasis:
  • Noninvasive infection of the skin, hair, mucous membranes, and nails
  • Typically seen in the 1st year of life, and almost all cases occur within the 1st decade
  • Caused by a T-cell immunodeficiency resulting in a poor response to candidal antigens. Patients lack a delayed-type hypersensitivity reaction to intradermal injection of candidal antigens.

Candidiasis - DIAGNOSIS

Candidiasis - signs & symptoms

Candidiasis - history

• Recurrent infection:
  • In oral thrush, reinfection may occur from nipples, pacifiers, or toys (see “General Prevention” and “Alert”).
  • In recurrent vaginitis, bacterial or non-albicans Candida species infections are possible.
• Recent antibiotic use: Oral thrush often occurs in infants, but may occur in normal older children after treatment with systemic antibiotics.
• Predisposing conditions: Systemic dissemination of infection is more likely with impaired immunity.
• Visual changes or discomfort: Features of endophthalmitis include eye pain, blurred vision, scotomata, and photophobia.

Candidiasis - physical exam

• Oral lesions: Buccal or lingual mucosa, gingiva, and tongue lesions have a characteristic white, friable pseudomembrane that when scraped away, reveals reddened, denuded, and sometimes ulcerated mucosa.
• Rash:
  • The rash of monilial diaper dermatitis is initially scattered.
  • Erythematous papules progress and coalesce into a deeply erythematous, weeping, confluent rash with a scaling border and satellite lesions.
  • In neonates with congenital candidiasis, skin findings include vesicles, pustules, or a diffuse macular rash.
  • Patients with invasive candidiasis may also present with a diffuse, erythematous rash.

Candidiasis - tests

Dilated retinal examination (by an ophthalmologist): Endophthalmitis, a sight-threatening complication, should be excluded in all patients with candidemia.

Candidiasis - lab

• Direct light microscopic examination of specimen:
  • Clinical diagnosis of mucosal, cutaneous, and vaginal candidiasis can be confirmed by microscopic examination of material scraped gently from lesions.
  • KOH preparation (10% or 20% potassium hydroxide) allows visualization of the long, branching, hyphae of C. albicans.
  • Vaginal pH remains normal (<4.5) with vaginal candidiasis.
• Fungal culture:
  • Candida species can be isolated from culture of mucosal or cutaneous scrapings, blood, urine, CSF, bone marrow, tissue biopsy, abscess aspirate, and bronchoalveolar lavage fluid.
  • However, the sensitivity of blood culture is only 50–60% in patients with invasive candidiasis.

Candidiasis - imaging

CT scan and echocardiogram: Important to identify deep organ lesions (liver, spleen, brain, kidney, or heart) associated with disseminated infection

Candidiasis - differencial diagnosis

• Oral lesions:
  • Aphthous stomatitis
  • Acute necrotizing gingivitis
  • Herpes gingivostomatitis
  • Other viral causes of stomatitis (e.g., coxsackievirus)
• Diaper dermatitis: Atopic, seborrheic, bacterial, or occlusional
• Intertriginous infections: Seborrheic and atopic dermatitidis
• Vaginitis
• Congenital candidiasis:
  • Viral infections (especially herpes viruses)
  • Bacterial infections
  • Benign neonatal skin conditions
• Invasive candidiasis: Bacterial infection or other fungal infection
• Chronic mucocutaneous candidiasis: HIV

Candidiasis - TREATMENT

Candidiasis - medication

• Oral candidiasis:
  • Nystatin suspension until 2 days after the lesions have cleared. Miconazole oral gel, although more effective, is not yet available in the US.
  • In older patients, nystatin as a swish-swallow suspension or in oral tablet form for >7 days is effective. Clotrimazole lozenges are also effective; 10 mg dissolved in mouth 5 times daily for 7 days
  • Gentian violet is no longer recommended.
  • Fluconazole and ketoconazole are effective for infections that are persistent or occur in immunocompromised hosts. Azole-resistant C. albicans has been described in HIV-infected individuals with recurrent infection.
• Esophageal candidiasis:
  • A therapeutic trial with fluconazole for patients with presumed esophageal candidiasis is a cost-effective alternative to endoscopy; symptoms should resolve within 7 days after the start of therapy. A 14–21-day course is recommended. Itraconazole solution and IV amphotericin B are acceptable alternatives.
• Cutaneous or intertriginous candidiasis and candidal diaper dermatitis:
  • Both are treated by keeping the area dry and using nystatin cream (100,000 U/g q.i.d.) until the rash has cleared.
  • Topical regimens of clotrimazole 1%, miconazole 2%, ketoconazole 2%, and econazole 1% are also effective.
• Uncomplicated vaginal candidiasis:
  • Topical agents are highly effective in uncomplicated infections (cure rates >80%): clotrimazole, miconazole, butoconazole, and terconazole (dose varies with 1-, 3-, or 7-day treatment).
  • Oral agents are also effective: Fluconazole (10 mg/kg up to 150 mg as a single dose), ketoconazole (400 mg daily for 5 days), and itraconazole (200 mg b.i.d. for 1 day or 200 mg daily for 3 days)
• Complicated vaginal candidiasis:
  • Extend antimycotic therapy to 7–14 days
  • Non-albicans species of Candida usually respond to topical boric acid (600 mg/d for 14 days). Azole-resistant C. albicans infections are extremely rare in the immunocompetent host.
• Recurrent vaginitis (more than 4 episodes of proven infection during a 12-month period):
  • Usually caused by azole-susceptible C. albicans
  • Induction therapy with 2 weeks of a topical or oral azole is followed by a maintenance regimen for 6 months.
  • Suitable maintenance regimens include fluconazole (150 mg weekly), ketoconazole (100 mg daily), itraconazole (100 mg every other day), or daily therapy with a topical azole.
• Systemic or disseminated candidiasis:
  • Begin treatment in hospital because of severity of illness, underlying disease process, and need for the IV route of drug administration.
  • Address predisposing factors (e.g., removal of indwelling catheters).
  • Antifungal agents commonly used in children include amphotericin B, fluconazole, or the combination of fluconazole plus amphotericin B (with the amphotericin B administered for the 1st 5 or 6 days only).
• Fluconazole may be used in those infected with a Candida species known to be fluconazole susceptible.
• Flucytosine could be considered in combination with amphotericin B for more severe infections.
• Lipid-based amphotericin B: 3–6 mg/kg/d IV. Appropriate for patients who are refractory to, intolerant of, or at high risk of being intolerant of conventional amphotericin B preparations
• Intolerance to conventional amphotericin B is usually defined as initial renal insufficiency (creatinine clearance <25 mL/min), significant rise in creatinine during therapy (to 2.5 mg/dL in adults or 1.5 mg/dL in children), or severe acute administration-related toxicity. The toxicity of amphotericin (rigors, anemia, thrombocytopenia, and renal failure) requires close monitoring and may limit its use.
• Duration of therapy is longer for candidal meningitis (4 weeks), endophthalmitis (6–12 weeks), endocarditis (>6 weeks following surgical therapy), and osteomyelitis (6–12 months).

Pitfalls:

• Failure to eliminate source of reinfection. Recurrent thrush in a breast-fed infant may indicate C. albicans colonization of the mother’s nipples; this can be eliminated by treatment of the nipples with nystatin cream.
• Failure to consider that symptoms of persistent vaginitis may be caused by non-albicans Candida species or by bacteria (see “Vaginitis”)
• Failure to maintain a high index of suspicion for invasive candidiasis in an immunocompromised patient. Persistent fevers despite antibiotic therapy, diffuse rash, and visual complaints are important clues.

Candidiasis - FOLLOW UP

Candidiasis - prognosis

• Invasive candidiasis is associated with significant morbidity and mortality.
• In children, candidemia is associated with an attributable mortality of 10%.

Candidiasis - bibliography

1. Mermel LA, Farr BM, Sheretz RJ, et al. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis. 2001;32:1249–1272.
2. Pappas PG, Rex JH, Sobel JD, et al. Guidelines for the treatment of candidiasis. Clin Infect Dis. 2004;38:161–189.
3. Zaoutis TE, Argon J, Berlin JA, et al. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: A propensity analysis. Clin Infect Dis. 2005;41:1232–1239.

Candidiasis - CODES

Candidiasis - icd9

112.9 Candidiasis

Candidiasis - FAQ

• Q: When should an older child with thrush be worked up for possible immunodeficiency?
• A: Thrush in the older child is usually caused by recent antibiotic or steroid treatment. If no apparent cause is found, an immunologic evaluation that includes HIV testing should be considered.

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

More About Vaginal candidiasis

• Back to disease: Vaginal candidiasis: Introduction
• Next Book Extract About Vaginal candidiasis: Surveys relating to Vaginal candidiasis
• More Book Extracts: All Online Books for Vaginal candidiasis

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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

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