What medications are used to treat fungal infections in pediatric patients?

Medications for Treating Fungal Infections in Pediatric Patients

The treatment of fungal infections in pediatric patients requires specific antifungal agents tailored to the type of infection, with echinocandins, azoles, and polyenes being the primary medication classes used based on the specific pathogen and site of infection. 1

Systemic Antifungal Medications for Invasive Fungal Infections

Echinocandins

• Caspofungin: Recommended with a loading dose of 70 mg/m² followed by 50 mg/m²/day IV for invasive candidiasis (A-I) 1
• Micafungin: Recommended at 2-4 mg/kg/day IV for children <40 kg with invasive candidiasis (A-I) 1
• Anidulafungin: Can be used at 3 mg/kg as a single loading dose followed by 1.5 mg/kg/day for invasive candidiasis (B-II) 1

Polyenes

• Liposomal amphotericin B: Recommended at 3 mg/kg/day IV for invasive candidiasis (A-I) and can be used for prophylaxis at 1 mg/kg IV every other day in high-risk patients 1
• Conventional amphotericin B (deoxycholate): Used at 0.5-1.5 mg/kg/day IV for invasive fungal infections, though associated with more toxicity than liposomal formulations 1

Azoles

• Fluconazole: Recommended at 8-12 mg/kg/day IV or orally (max 400 mg) for invasive candidiasis (B-I) 1
• Voriconazole: For children ≥2 years with invasive aspergillosis or candidiasis, dosed at 9 mg/kg IV every 12 hours on day 1, then 8 mg/kg twice daily IV (B-I) 1
• Itraconazole: Used at 5 mg/kg/day of oral suspension in children ≥2 years in two divided doses for prophylaxis and treatment of fungal infections 1
• Posaconazole: For patients ≥13 years, 300 mg daily as gastro-resistant tablet or 600 mg daily in three divided doses as oral suspension 1

Treatment by Specific Fungal Infection Type

Candida Infections

Oropharyngeal Candidiasis

• Fluconazole: 6 mg/kg on day 1, then 3-6 mg/kg daily for 7-14 days; shown to be more effective than nystatin with 86% clinical cure rate versus 46% 1, 2
• Itraconazole oral solution: 2.5 mg/kg twice daily or 5 mg/kg once daily for 7-14 days 1
• Nystatin suspension: Alternative for mild cases, but with lower efficacy (only 11% mycological eradication compared to 76% with fluconazole) 2

Esophageal Candidiasis

• Fluconazole: 6 mg/kg on day 1, then 3-6 mg/kg daily for 14-21 days (AI) 1
• Itraconazole oral solution: 2.5 mg/kg twice daily or 5 mg/kg once daily for 14-21 days (AI) 1
• Low-dose amphotericin B: 0.3 mg/kg/day IV for minimum 7 days for refractory cases (BII) 1

Invasive Candidiasis/Candidemia

• First-line options: Echinocandins (caspofungin, micafungin) or liposomal amphotericin B 1
• Duration: Treat for 14 days after negative blood cultures and resolution of symptoms 3
• Central venous catheters should be removed when feasible in children with candidemia 1

Aspergillus Infections

Invasive Aspergillosis

• Voriconazole: First-line for children >2 years (A-I) 1
• Liposomal amphotericin B: Alternative option at 3 mg/kg/day 1
• Caspofungin: Alternative option when azoles are contraindicated 1

Prophylaxis in High-Risk Patients

• Itraconazole: For children ≥2 years (A-II) 1
• Posaconazole: For children ≥13 years (A-II) 1
• Voriconazole: For children >2 years (A-II) 1

Special Considerations in Pediatric Patients

Neonatal Fungal Infections

• Fluconazole: 3-6 mg/kg twice weekly for prophylaxis in neonates <1000g in NICUs with high incidence of invasive candidiasis (A-I) 3
• Amphotericin B deoxycholate: 1.0 mg/kg/day for treatment of neonatal candidiasis 1
• Micafungin: Alternative for neonatal candidiasis, though dosing may need adjustment 1

Monitoring and Safety

• Therapeutic drug monitoring (TDM) is recommended when using itraconazole, posaconazole, and voriconazole in children 1
• Potential side effects:
  • Azoles: Hepatotoxicity, QT prolongation, visual disturbances (voriconazole) 4
  • Amphotericin B: Nephrotoxicity, infusion-related reactions 5
  • Echinocandins: Generally well-tolerated with minimal adverse effects 4

Treatment Algorithm Based on Infection Site and Severity

1. Superficial fungal infections (skin, mucous membranes):

   • First-line: Topical antifungals (azoles, allylamines) 6
   • For extensive or refractory cases: Oral fluconazole or itraconazole 7

2. Invasive candidiasis:

   • First-line: Echinocandin (caspofungin, micafungin) or liposomal amphotericin B 1
   • Step-down therapy: Fluconazole (if isolate is susceptible) 1

3. Invasive aspergillosis:

   • First-line: Voriconazole (>2 years) 1
   • Alternative: Liposomal amphotericin B or caspofungin 1

4. CNS fungal infections:

   • First-line: Liposomal amphotericin B with or without flucytosine 1
   • Alternative: Voriconazole (for aspergillosis) 1

The choice of antifungal agent should be guided by the specific pathogen, site of infection, patient's age, underlying conditions, and local epidemiology of antifungal resistance patterns 1, 8.