Gentamicin Pharmacokinetics and Monitoring in Pediatric Patients with Febrile Neutropenia

Abstract

Background: The pharmacokinetics of gentamicin in pediatric patients with febrile neutropenia is described, and the adequacy of initial dosing of once-daily gentamicin assessed at Queensland's largest Children's Hospital.

Methods: Data were retrospectively collected from all pediatrics with febrile neutropenia admitted over a 2-year period who had at least 2 gentamicin concentration-time measurements (a paired set within 1 dosing interval). Gentamicin clearance, volume of distribution, area under the concentration-time curve from 0 to 24 hours postdose (AUC0-24), and maximum concentration values were estimated with log-linear regression using each paired set. The percentage of paired sets associated with gentamicin exposure within predefined hospital targets was calculated, and exposure was examined in relation to the bacterial culture status.

Results: Data were collected from 69 patients [median (interquartile range) age 3.7 years (2.2-8.9)] and comprised 121 paired concentration sets characterizing 80 separate admissions. Median (interquartile range) gentamicin clearance and volume of distribution were 8.1 L·h·70 kg (5.8-12.4) and 21.8 L/70 kg (16.9-29.5), respectively. Predefined hospital exposure targets were achieved for both AUC0-24 and maximum concentration for 10% of paired sets; one or the other of these targets were met for 36% of paired sets, and neither target was achieved for 54% of paired sets. Achievement of targets improved with repeated monitoring during the same admission. Median AUC0-24 achieved was significantly higher in patients with a confirmed Gram-negative infection compared with those without 71 (50-91) mg·h·L versus 55 (40.8-67.5) mg·h·L, respectively (P = 0.003). Over the study period, a median gentamicin dose of 10.8 and 6.4 mg/kg was estimated to be necessary to achieve an AUC target of 80 mg·h·L in children ≤10 years and >10 years of age.

Conclusions: Based on a log-linear method of analysis, current dosing seems to be consistently producing gentamicin exposure below predefined pharmacokinetic targets, suggesting that an increase in the recommended starting dose of gentamicin may be required.