G. W. 't Jong,1 J. McKitrick,2 B. Bewick,3 R. Ariano,3 M. Narvey4; 1Manitoba Institute for Child Health (MICH), Winnipeg, MB, Canada, 2Health Sciences Centre, Winnipeg, MB, Canada, 3St. Boniface General Hospital, Winnipeg, MB, Canada, 4Manitoba Institute for Child Health (MICH), Health Sciences Centre, MB, Canada
BACKGROUND: Gentamicin (GN) is used for IV treatment of neonatal infections. Gentamicin is effective in treating common gram negative pathogens in Canada. Dosing protocols of GN in neonates <35 wks corrected GA (CGA) range from 2.5 to 5 mg/kg/dose given every 8 to 24 hours depending on patient’s CGA and/or birth weight. The primary aim was to confirm that GN 5 mg/kg Q48h in neonates less than 35 weeks CGA resulted in GN serum levels within accepted target (trough: 0.5-2 mg/L; peak 6-12 mg/L).
METHODS: Patients admitted to the NICU of the Health Sciences Centre and St. Boniface General Hospital in Winnipeg, Canada less than 35 weeks CGA and initiated on GN (with either vancomycin or a β lactam antibiotic) received a dose of 5 mg/kg IV every 48 hours, if warranted. PK was calculated using a linear one compartment model to extrapolate expected serum levels at exactly 1, 24, and 48 post dose. Volume of distribution (Vd) and half-life (t1/2) were then calculated using the 1 hour and 24 hour post dose serum levels. 44 treatment courses in 36 different patients were included in the PK analysis using postnatal age (PNA) and CGA.
RESULTS: PNA 14 d at 24 h (1.7 ± 0.3 mg/L vs. 1.1 ± 0.7 mg/L, p = 0.0016 resp.) and 48 h (0.34 ± 0.14 mg/L vs. 0.2 ± 0.2 mg/L, p = 0.027 resp.), but CGA had no influence. Mean (± SD) t1/2 of GN at 24 h significantly decreased as PNA increased (10.2 ± 1.6 hr vs. 8.3 ± 2.3 hr, p = 0.012 resp.) but did not differ based on CGA.
CONCLUSION: A GN dose of 5 mg/kg Q48h in neonates <35 w CGA and <14 d PNA results in acceptable therapeutic serum levels. While the 48 h level fell below the acceptable serum level target the clinical significance of lower 48 h levels is disputable and would benefit from further study. PNA rather than CGA may be a reliable determinant for predicting GN levels associated with extended interval GN dosing in neonates.