Recommended Dosing of Amphotericin B in Neonates
For neonates with invasive candidiasis, amphotericin B deoxycholate should be administered at a dose of 1 mg/kg/day intravenously as a single daily dose. 1
Amphotericin B Formulations for Neonates
Conventional Amphotericin B (Deoxycholate)
- First-line therapy for invasive candidiasis in neonates at 1-1.5 mg/kg/day intravenously as a single daily dose 1
- Pharmacokinetics in neonates are relatively poorly defined, leading to some uncertainty regarding optimal dosage for hematogenous Candida meningoencephalitis (HCME) 1
- Nephrotoxicity appears less pronounced in neonates compared to older children and adults 2
- Monitoring of renal function and potassium levels is essential during treatment 2
- Sodium supplementation (4 mEq/kg/day) may significantly reduce nephrotoxicity 3
Liposomal Amphotericin B
- Recommended at 2.5-7 mg/kg/day intravenously as a single daily dose 1
- Not approved for use in infants <1 month of age 1
- Higher doses (5-7 mg/kg/day) have shown effectiveness with fungal eradication achieved in 95% of cases 4
- Better safety profile than conventional amphotericin B, particularly regarding nephrotoxicity 5, 6
- Consider for neonates with renal impairment or those at high risk for nephrotoxicity 3
Amphotericin B Lipid Complex (ABLC)
- Alternative option at 2.5-5 mg/kg/day intravenously as a single daily dose 1
- Graded as C-II (lower evidence) due to relative paucity of clinical data 1
- Preclinical data suggests effectiveness for HCME 1
Clinical Considerations
Monitoring During Treatment
- Monitor renal function with serum creatinine at baseline and regularly during treatment 2
- Monitor serum potassium levels due to risk of hypokalemia (<3.0 mmol/L) which occurs in approximately 17% of treated neonates 2
- Follow blood cultures to document clearance of infection 4
Duration of Therapy
- Median duration of therapy is approximately 18 days 4
- Continue treatment until fungal eradication is achieved (median time to eradication: 8-11 days) 4
- For HCME, longer treatment courses may be necessary 1
Special Considerations
- Elevated serum creatinine typically resolves by the end of amphotericin B therapy in most neonates 2
- Consider higher doses of liposomal amphotericin B (up to 7 mg/kg/day) for difficult-to-treat infections 4
- First-line therapy with high-dose liposomal amphotericin B may achieve more rapid fungal eradication than when used as second-line therapy 4
Alternative Antifungal Options for Neonates
- Fluconazole: 12 mg/kg/day with consideration of a 25 mg/kg loading dose 1
- Micafungin: 4-10 mg/kg/day IV (higher doses for suspected HCME) 1
- Caspofungin: 25 mg/m²/day 1
Common Pitfalls and Caveats
- Underestimating the importance of monitoring renal function and electrolytes during treatment 2
- Premature discontinuation of therapy before achieving fungal eradication 4
- Failure to consider CNS involvement (HCME) when treating neonatal candidiasis 1
- Not adjusting dosing based on the specific amphotericin B formulation being used 1