Thrush

C albicans causes thrush when normal host immunity or normal host flora is disrupted. Overgrowth of yeast on the oral mucosa leads to desquamation of epithelial cells and accumulation of bacteria, keratin, and necrotic tissue. This debris combines to form a pseudomembrane, which may closely adhere to the mucosa. This membrane is usually not large but may rarely involve extensive areas of edema, ulceration, and necrosis of the underlying mucosa.

Affected neonates are typically colonized by C albicans during passage through the birth canal. Hence, the risk for thrush is increased when the mother has an active vaginal yeast infection. Other sources of transmission to neonates include colonized breasts (for breastfed infants), hands, and/or improperly cleaned bottle nipples. Kissing has also been implicated.

C albicans frequently and asymptomatically inhabits the GI tract of many children and adults, and the GI tract has been implicated as a reservoir for yeast contamination of the perineum. Thus, candidal diaper rash frequently occurs in conjunction with thrush.

A systematic review and meta-analysis reported that the prevalence of oral candidiases caused by non-albicans Candida species in sub-Saharan African HIV patients was 33.5% [95% confidence interval (CI) 30.9-36.39%]. Non-albicans Candida species found included C glabrata (23.8%; 109/458), C tropicalis (22%; 101/458) and C krusei (10.7%; 49/458).[1]

A study by Karajacob et al found that nearly one third of the oral Candida species isolated from cultures of patients with oral thrush were non-albicansCandida. C tropicalis was the most commonly isolated non-albicansCandida species (21.1%), and C glabrata was cultured from 15.8% of oral samples.[2]

Consider an underlying immune deficiency such as AIDS, especially in recurrent cases and in older infants. For chronic infection, chronic mucocutaneous candidiasis should be considered.

Systemic antibiotic use may disrupt the normal flora, promoting candidal overgrowth.

Use of systemic and inhaled steroids is associated with increased incidence of oral thrush.

An increased prevalence of oral candidiasis has been reported among patients with novel coronavirus disease (COVID-19). One review found that 10.74% of adults with COVID-19 had oral thrush, and another study reported oral thrush in 11.63% of pediatric patients.[3]

United States statistics

As many as 37% of newborns may develop thrush during the first months of life.

International statistics

Thrush is universal and is more common in poorly nourished populations.

Sex- and age-related demographics

Thrush occurs equally in males and females.

Thrush is rare during the first week of life. Incidence peaks around the fourth week of life; thrush is uncommon in infants older than 6-9 months. Thrush can occur, however, at any age in predisposed patients.

Thrush is considered a self-limited disease, but resolution is hastened by medical therapy.

Morbidity/mortality

Thrush is usually a mild and self-limited illness, although it may cause discomfort sufficient to disrupt feeding in a newborn. Consider the possibility of an underlying immunodeficiency when thrush occurs after early infancy or without a reasonable explanation.

Complications

Very rarely, extensive tracheal and esophageal involvement in thrush may lead to dysphagia and respiratory distress in otherwise healthy hosts.

Bronchopulmonary candidiasis has been reported.

Systemic dissemination may occur in immunosuppressed patients.

Candidal esophagitis is a common complication of thrush in immunocompromised patients. In one study, it was the most common opportunistic infection in adults with acquired immunodeficiency syndrome (AIDS) (13.3 episodes per 100 person-years).

Discuss thrush etiology and incidence as part of general reassurance to the parents of the healthy newborn or infant.

If indicated, offer information about the necessity of further evaluation for underlying immune dysfunction.

Parents of children with thrush usually notice a white coating in the child's mouth.

Infants may have trouble feeding in severe cases.

Medical history may include the following:

• Recent antibiotic or steroid use may suggest a predisposing cause.

A study found that the adverse effects of antibiotics such as amoxicillin were underreported as treatment with amoxicillin or amoxicillin-clavulanic acid commonly results in candidiasis. The study concluded that clinicians need information about both harms and benefits when prescribing antibiotics.[4, 5]

Diarrhea, rashes, failure to thrive, hepatosplenomegaly, or repeated infections suggest an underlying immunodeficiency.[6]

Maternal history may include the following:

• Vaginal candidiasis is a source of perinatal exposure to infection.

• HIV status may provide a clue to a predisposing factor.

Lesions often start as tiny focal areas that enlarge to white patches on oral mucosae (see the image below).

When scraped with a tongue blade, lesions are difficult to remove and leave behind an inflamed base that may be painful and may bleed.

Candidal infection in the diaper area may accompany thrush. Examine an infant with diaper dermatitis for oral lesions.[7]

Differentiate thrush from a coated tongue.

Thorough physical examination is critical, especially for patients with recurrent thrush and for older children. Pay attention to the child's growth, rash distribution, lymphadenopathy, hepatosplenomegaly, and other potential sites of infection (eg, mucocutaneous candidiasis[8, 9, 10]  ).

A relatively simple way to confirm the suspected diagnosis of thrush is to scrape the plaques with a tongue blade to reveal an inflamed and/or bleeding base.

Plaques can be cultured, although cultures are rarely indicated. A simple Gram stain demonstrates large, ovoid, gram-positive yeast.

A study by Tooyama et al looked to establish a reliable laboratory test for diagnosing oral candidiasis. The study found that concentrated rinse sampling is suitable for evaluating oral candidiasis.[11]

Diagnosis can be confirmed by simple histologic findings. Pseudohyphae and gram-positive yeast can be seen on Gram stain or with potassium hydroxide stain.

Although some anecdotal reports indicate no treatment is necessary for otherwise healthy neonates, no published studies support this assertion.[12]

In cases in which underlying immune dysfunction is suspected, consultation with an immunologist and infectious diseases specialist may be warranted for further evaluation.

No special diet is indicated.

Antifungal therapy generally hastens resolution of infection.[13, 14] The treatment of choice for thrush is fluconazole or oral nystatin suspension, although numerous antifungal agents are effective. Resistance to nystatin is rare, although the drug's contact killing makes it somewhat more difficult to use because it must be applied to all of the affected mucosal surfaces to be effective (unlike systemic therapies). Failures with nystatin are more common than with fluconazole.[15]

In older children and adults, antifungal medications should be swished around in the oral cavity and swallowed. Failure to do so may provide ineffective treatment for lesions in the posterior pharynx and esophagus. In younger patients, instruct parents to apply 1-2 mL of the solution to the inside of each cheek during each administration. Medication can also be directly applied to the lesions with a nonabsorbent swab or applicator. The best time to administer medication is between meals because this allows longer contact time.

Gentian violet solution should not be swallowed. Lozenges (troches) may be used if suspension preparations are unavailable.

These antifungal preparations have minimal adverse effects and few contraindications because they involve little or no systemic absorption. Aside from itraconazole, against which candidal resistance is increasing, other readily available antifungals are effective. If inability to adequately apply nystatin (or the oral cavity's normal flushing mechanisms) results in treatment failure, oral fluconazole or gentian violet are second-line agents.

Class Summary

The mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Nystatin (Mycostatin, Nilstat, Nystex)

DOC for oral thrush. No significant absorption from the intact skin, GI tract, or vagina. 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.

Amphotericin B deoxycholate (Fungizone Oral Suspension)

Produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.

Clotrimazole (Mycelex Troches)

Alters cell membrane. Very effective treatment in immunocompetent host. If susp not available (not available in the United States), troches (lozenges) can be used, but troche has been associated with elevated liver enzymes and GI adverse effects.

Miconazole oral (Daktar)

Not available in the United States. Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol; increases membrane permeability, causing nutrients to leak out, resulting in fungal cell death.

Gentian violet

Although inexpensive, efficacious for thrush refractory to other therapies. Solution stains clothing and mucosa intensely, causing undesirable cosmetic effects.

Fluconazole (Diflucan)

Azole antifungal with excellent bioavailability. Interferes with cell membrane and is eliminated via renal pathway.

Fungistatic activity. Synthetic PO antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.