What is the recommended treatment for oral thrush in a neonate?

Treatment of Oral Thrush in Neonates

For uncomplicated oral thrush in healthy term neonates, nystatin oral suspension 100,000 units (1 mL) four times daily for 7-14 days is the first-line treatment, while fluconazole 3-6 mg/kg daily for 7 days should be reserved as second-line therapy when nystatin fails or for premature/high-risk infants. 1, 2

First-Line Treatment: Nystatin

• Nystatin oral suspension (100,000 units/mL): 1 mL four times daily for 7-14 days is recommended by the American Academy of Pediatrics for healthy term infants 1, 2
• For premature and low birth weight infants, the FDA label indicates that 1 mL four times daily is effective based on limited clinical studies 2
• Apply using a dropper, placing one-half of the dose in each side of the mouth, and avoid feeding for 5-10 minutes to maximize mucosal contact 2
• Continue treatment for at least 48 hours after symptoms disappear and cultures confirm eradication of Candida 1, 2

Nystatin Administration Technique

• The preparation must be retained in the mouth as long as possible before swallowing to achieve therapeutic effect 2
• Treatment endpoint should be mycological cure, not just clinical resolution of visible patches 1

Second-Line Treatment: Fluconazole

When nystatin fails or for high-risk infants, fluconazole oral suspension 3-6 mg/kg once daily for 7 days is the preferred alternative 1, 3

• Fluconazole has a half-life of 55-90 hours in neonates, allowing once-daily dosing 1
• In a randomized trial, fluconazole achieved 100% clinical cure (15/15 infants) compared to only 32% (6/19) with nystatin (p<0.0001) 4
• For premature newborns (gestational age 26-29 weeks) in the first two weeks of life, administer the same mg/kg dose but every 72 hours due to prolonged half-life; after two weeks, dose once daily 3

Fluconazole Dosing by Age

• Full-term neonates >2 weeks old: 3-6 mg/kg once daily 1, 3
• Premature neonates <2 weeks old: Same mg/kg dose every 72 hours 3
• After 2 weeks in premature infants: Transition to once-daily dosing 3

Third-Line Option: Miconazole Gel

• Miconazole oral gel 15 mg every 8 hours achieves clinical cure rates of 85.1% versus 42.8-48.5% for nystatin 1
• However, miconazole carries significant risks: potential for airway obstruction in neonates due to viscous gel consistency, and concerns about generating triazole resistance 1, 5
• A case report documented near-asphyxiation of a 17-day-old infant from miconazole gel applied to maternal nipples 5
• Miconazole should only be used when fluconazole is unavailable and with extreme caution regarding aspiration risk 1, 5

Special Populations Requiring Systemic Therapy

Premature or low birth weight neonates with disseminated cutaneous candidiasis require systemic antifungal therapy, not just topical treatment 6

• Amphotericin B deoxycholate 0.5-1 mg/kg/day for a total dose of 10-25 mg/kg is used for disseminated disease 6
• For invasive neonatal candidiasis, amphotericin B deoxycholate 1 mg/kg daily or fluconazole 12 mg/kg daily for at least 3 weeks is recommended 6
• All neonates with suspected invasive candidiasis should undergo lumbar puncture and dilated retinal examination 6

Prophylaxis in High-Risk Settings

• In NICUs with invasive candidiasis rates >10%, fluconazole prophylaxis 3-6 mg/kg twice weekly for 6 weeks is recommended for infants <1000g 6, 1
• Oral nystatin 100,000 units three times daily for 6 weeks is an alternative when fluconazole is unavailable or resistance is a concern 6
• Prophylactic oral nystatin significantly reduced invasive candidiasis in extremely low birth weight (ELBW) and very low birth weight (VLBW) infants (1.8% vs 14.2%, p=0.004) 7

Breastfeeding-Associated Thrush

When oral thrush occurs in breastfed infants, simultaneous treatment of both mother and infant is essential to prevent reinfection 1, 8

• Treat infant with nystatin or fluconazole as above 1, 8
• Mother should apply miconazole cream to nipples/areola after each feeding 1, 8
• Keep affected areas dry between feedings 8

Critical Pitfalls to Avoid

• Inadequate treatment duration: Stopping treatment when white patches disappear clinically without confirming mycological cure leads to recurrence 1, 2
• Improper nystatin administration: Swallowing immediately without mucosal contact time reduces efficacy 2
• Missing maternal nipple candidiasis: Failure to treat breastfeeding mothers simultaneously causes reinfection cycles 1, 8
• Miconazole aspiration risk: The viscous gel can cause airway obstruction in neonates; apply only small amounts directly to oral mucosa, never to nipples for indirect transfer 1, 5
• Premature use of fluconazole: Reserve for nystatin failures or high-risk infants to minimize resistance development 1, 9

Diagnostic Considerations

• While clinical diagnosis based on white plaques is standard, recent evidence suggests C. albicans may not always be present in clinically diagnosed "thrush" 10
• Consider bacterial and candidal cultures from lesional areas, particularly in persistent or atypical cases 1
• Evaluate for underlying immunodeficiency or other predisposing factors in older infants or those with recurrent infections 9