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Increased level/dose ratio of amphotericin-B in premature infants with renal failure
1Department of Pediatrics, Wakayama Medical College, Japan.
Insights
Continuous intravenous infusion of amphotericin-B effectively treated systemic candidiasis in extremely low birthweight infants. Serum drug levels correlated with renal function, aiding dosing adjustments for this vulnerable population.
Area of Science:
- Neonatal Medicine
- Infectious Diseases
- Pharmacology
Background:
- Systemic candidiasis poses a significant threat to extremely low birthweight (ELBW) infants.
- Limited treatment options exist for invasive fungal infections in this high-risk neonatal population.
- Amphotericin-B is a critical antifungal agent, but its use in neonates requires careful dosing and monitoring.
Purpose of the Study:
- To evaluate the efficacy and safety of continuous intravenous infusion amphotericin-B in ELBW infants.
- To determine serum amphotericin-B levels and their correlation with dosage and renal function.
- To establish a reference for therapeutic drug monitoring in neonatal candidiasis.
Main Methods:
- Continuous intravenous infusion of amphotericin-B was administered to ELBW infants with systemic candidiasis.
- Candida species identification and minimal inhibitory concentration (MIC) determination were performed.
- Serum amphotericin-B levels, daily doses, and serum creatinine were monitored.
- Correlation analysis was used to assess the relationship between drug levels, dose, and renal function.
Main Results:
- Nine out of eleven ELBW infants survived systemic candidiasis treated with amphotericin-B.
- Serum amphotericin-B levels generally exceeded the MICs of isolated Candida strains.
- Serum drug levels did not correlate with the daily dose but showed a significant correlation with serum creatinine.
- The ratio of serum level to daily dose (L/D ratio) predicted by serum creatinine (L/D ratio = 0.223 x serum creatinine + 1.11).
- Adverse effects associated with amphotericin-B were minimal.
Conclusions:
- Continuous intravenous infusion amphotericin-B is an effective treatment for systemic candidiasis in ELBW infants.
- Serum creatinine is a valuable predictor of amphotericin-B levels during continuous infusion, aiding dose adjustments.
- This dosing strategy offers a potential reference for managing neonatal candidiasis, improving therapeutic outcomes.
Abstract:
We introduced continuous intravenous infusion of amphotericin-B (AMPH-B) to extremely low birthweight (ELBW) infants (< 1000 g) with or without renal failure as a single agent for treating definite or probable systemic candidiasis. The species of Candida isolated from blood or tracheal aspirate or urine were C. albicans in seven infants, C glabrata in two, C. tropicalis in one and C. parapsilosis in one. The minimal inhibitory concentrations (MIC) of AMPH-B required against these isolates were less than 0.2 micrograms/mL except for that against one strain of C. albicans (0.78 microgram/mL). Serum AMPH-B levels were 0.31-0.78 (0.51 +/- 0.14) micrograms/mL when doses of 0.2-0.55 (0.32 +/- 0.11) mg/kg per day were being administered. The serum level was higher than the MIC of each isolate in all but one infant who died of disseminated intravascular coagulation and Candida pneumonia. Another infant died of congenital heart disease. The other nine infants survived. The serum level showed no correlation with the daily dose. The ratio of the serum level to the daily dose (L/D ratio) showed a significant correlation to serum creatinine (r = 0.787) and the linear regression curve followed the equation: L/D ratio = 0.223 x serum creatinine + 1.11 (P < 0.01). Few adverse effects due to AMPH-B were noted. Our data may give a simple reference to serum AMPH-B levels during continuous intravenous infusion from the dose and the serum creatinine level.