Home/Pharmacology/Pediatric Anti-Fungal Agents: Classification, Dosage, and Future
Pediatric Anti-Fungal Agents: Classification, Dosage, and Future
1. Classification and Overview
A. Polyenes
Key Agents: Amphotericin B (conventional and lipid formulations)
Mechanism: Bind to ergosterol in fungal cell membranes, creating pores that lead to cell death. Higher affinity for fungal ergosterol compared to human cholesterol provides selective toxicity.
Formulations:
Conventional Amphotericin B deoxycholate
Lipid complex (ABLC)
Liposomal formulation (L-AMB)
Colloidal dispersion (ABCD)
B. Azoles
Subclasses:
Triazoles:
First generation: Fluconazole, Itraconazole
Second generation: Voriconazole, Posaconazole, Isavuconazole
Imidazoles: Ketoconazole (limited systemic use in pediatrics)
Concurrent use of other nephrotoxic agents requires careful consideration
Azoles:
Concurrent use of contraindicated medications (CYP3A4 substrates)
Severe hepatic dysfunction (requires dose adjustment)
Echinocandins:
Hypersensitivity to echinocandin class
B. Special Populations
Neonates:
Limited data on newer azoles
Modified dosing schedules required
Careful monitoring of hepatic/renal function
Renal Impairment:
Dose adjustment for azoles
Avoid conventional amphotericin B
Hepatic Impairment:
Monitor LFTs closely with azoles
Dose adjustment may be necessary
5. New Developments and Future Directions
A. Recent Advances
Fosmanogepix (APX001):
Novel mechanism: Gwt1 inhibitor
Broad-spectrum activity
Phase 2 studies ongoing in pediatric populations
Rezafungin:
Novel echinocandin
Extended half-life allowing weekly dosing
Pediatric trials in planning phase
Olorofim:
Novel mechanism: DHODH inhibitor
Active against resistant Aspergillus
Oral formulation available
B. Emerging Therapeutic Strategies
Combination Therapy:
Echinocandin + azole for resistant infections
Ongoing studies in pediatric populations
Immunotherapy:
Antifungal monoclonal antibodies
CAR-T cell therapy for invasive fungal infections
Precision Medicine:
Pharmacogenetic testing for azole metabolism
Real-time therapeutic drug monitoring
6. Therapeutic Drug Monitoring
A. Indications for TDM
Required:
Voriconazole (all pediatric patients)
Posaconazole (prophylaxis and treatment)
Consider:
Itraconazole in severe infections
Isavuconazole in selected cases
B. Target Levels
Drug
Prophylaxis
Treatment
Voriconazole
1-5.5 mg/L
2-5.5 mg/L
Posaconazole
>0.7 mg/L
>1 mg/L
Itraconazole
>0.5 mg/L
>1 mg/L
Note: This reference guide is based on current pediatric clinical practice guidelines and recent literature. Regular updates are recommended as new evidence emerges. Therapeutic decisions should be individualized based on patient factors, local resistance patterns, and institutional guidelines.
Age-specific considerations: FDA approved for children ≥2 years
Adult Dosage
Microsize: 500-1000 mg/day divided BID
Ultramicrosize: 375-750 mg/day divided BID
Duration: 2-6 weeks for skin, 4-8 weeks for hair, 6-12 months for nails
Indications
Tinea capitis (particularly T. tonsurans)
Dermatophyte infections resistant to other therapy
Onychomycosis
Extensive tinea corporis
Contraindications
Porphyria
Severe liver disease
Pregnancy category X
Systemic lupus erythematosus
Pediatric Considerations:
Take with fatty meals to improve absorption
Monitor growth in long-term therapy
Regular CBC and liver function monitoring recommended
Adverse Effects
Photosensitivity
Headache
Gastrointestinal disturbances
Hepatotoxicity (rare)
Ketoconazole
Pediatric Dosage
Topical: Apply 1-2 times daily
Oral (limited use): 3.3-6.6 mg/kg/day
Maximum daily dose: 200 mg/day oral
Age-specific considerations: Oral form not recommended in children
Adult Dosage
Topical: Apply 1-2 times daily
Oral: 200-400 mg daily
Shampoo: Use 2 times per week
Indications
Seborrheic dermatitis
Pityriasis versicolor
Tinea infections (topical)
Candida skin infections
Contraindications
Acute or chronic liver disease
Use of CYP3A4 substrates
Pregnancy category C
Pediatric Considerations:
Oral form rarely used due to hepatotoxicity risk
Monitor for local irritation with topical use
Avoid eye contact with shampoo formulation
Adverse Effects
Hepatotoxicity (oral)
Adrenal suppression
Local irritation (topical)
Multiple drug interactions (oral)
Ciclopirox
Pediatric Dosage
Topical cream/solution: Apply 2 times daily
Nail lacquer: Apply daily (age >16 years)
Shampoo: Twice weekly
Age-specific considerations: Limited data in young children
Adult Dosage
Topical: Apply 2 times daily
Nail lacquer: Apply daily to affected nails
Duration: Based on clinical response
Indications
Superficial fungal infections
Seborrheic dermatitis
Onychomycosis (nail lacquer)
Tinea pedis/corporis/cruris
Contraindications
Hypersensitivity to ciclopirox
Not for ophthalmic use
Nail lacquer not for use in children
Pediatric Considerations:
Safety not established in children <6 years
Avoid application to large areas
Monitor for local reactions
Adverse Effects
Local burning sensation
Contact dermatitis
Nail disorders (with lacquer)
Periungual erythema
Econazole
Pediatric Dosage
Topical cream: Apply 1-2 times daily
Duration: 2-4 weeks typically
Maximum daily dose: Based on affected area
Age-specific considerations: Safe for use in infants >1 month
Adult Dosage
Topical: Apply 1-2 times daily
Duration: 2-4 weeks for skin infections
Continue treatment for 1 week after symptoms resolve
Indications
Tinea infections
Cutaneous candidiasis
Pityriasis versicolor
Diaper dermatitis with candidal infection
Contraindications
Hypersensitivity to econazole
Not for ophthalmic use
Caution in first two weeks of life
Pediatric Considerations:
Well tolerated in infants and children
Monitor for local irritation
Ensure proper application technique
Adverse Effects
Local irritation
Burning sensation
Pruritus
Contact dermatitis (rare)
Card 1 of 1
Disclaimer
The notes provided on Pediatime are generated from online resources and AI sources and have been carefully checked for accuracy. However, these notes are not intended to replace standard textbooks. They are designed to serve as a quick review and revision tool for medical students and professionals, and to aid in theory exam preparation. For comprehensive learning, please refer to recommended textbooks and guidelines.
Speech
To listen to this article, select the text and click play.
