Recommended amikacin doses in newborns often produce excessive serum levels

Area of Science:

• Neonatal pharmacology
• Infectious disease management

Background:

• Drug-resistant Enterobacter cloacae emerged in 1980, making amikacin the preferred aminoglycoside for suspected neonatal sepsis.
• Standard amikacin dosing guidelines were established for neonatal intensive care unit (NICU) infants.

Purpose of the Study:

• To evaluate amikacin blood levels in neonatal intensive care unit (NICU) infants receiving standard doses.
• To determine if current dosing leads to potentially toxic drug concentrations in different infant weight groups.

Main Methods:

• Amikacin loading and maintenance doses were administered to 18 infants (< or = 1,000 gm and > 1,000 gm).
• Peak and trough amikacin levels were measured one hour and 11.5 hours post-infusion, respectively.
• Drug levels were compared between infant weight groups and to adult toxic ranges.

Main Results:

• Infants weighing < or = 1,000 gm had significantly higher trough amikacin levels (16.6 microg/ml) compared to larger infants (6.5 microg/ml).
• A higher proportion of infants < or = 1,000 gm (70%) had peak and/or trough levels in the potentially toxic adult range compared to larger infants (29%).
• Excessive amikacin levels were observed in both infant groups, suggesting current dosing may be inappropriate.

Conclusions:

• Current amikacin dosage schedules may result in excessive and potentially toxic blood levels in neonatal intensive care unit (NICU) infants, particularly those weighing < or = 1,000 gm.
• Individualized therapy and therapeutic drug monitoring are essential for optimizing amikacin use in very low birthweight infants.
• Further research is needed to establish weight-specific dosing protocols for amikacin in neonates.