Gentamicin Pharmacokinetics and Monitoring in Pediatric Febrile Neutropenic Patients.

BACKGROUND: The pharmacokinetics of gentamicin in pediatric febrile neutropenia patients 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 two-year period who had at least two gentamicin concentration-time measurements (a paired set within one dosing interval). Gentamicin clearance (CL), volume of distribution (Vd), area under the concentration-time curve from 0 to 24 hours post-dose (AUC0-24), and maximum concentration (Cmax) values were estimated using log-linear regression using each paired set. The percentage of paired sets associated with gentamicin exposure within pre-defined hospital targets was calculated and exposure was examined in relation to bacterial culture status.

RESULTS: Data were collected from 69 patients (median [IQR] age 3.7 years [2.2, 8.9]) and comprised 121 paired concentration sets characterizing 80 separate admissions. Median [IQR] gentamicin CL and Vd were 8.1 L/h/70 kg [5.8, 12.4] and 21.8 L/70 kg [16.9, 29.5], respectively. Pre-defined hospital exposure targets were achieved for both AUC0-24 and Cmax 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 to 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 appears to be consistently producing gentamicin exposure below pre-defined pharmacokinetic targets, suggesting that an increase in the recommended starting dose of gentamicin may be required.