title: Population Pharmacokinetics and Dosing Considerations for Gentamicin in Newborns with Suspected or Proven Sepsis Caused by Gram-Negative Bacteria.
abstract: The aim of this study was to describe the population pharmacokinetics (PK) of gentamicin in neonates with suspected or proven Gram-negative sepsis and determine the optimal dosage regimen in relation to the bacterial MICs found in this population. Data were prospectively collected between October 2012 and January 2013 in the Neonatal Intensive Care Unit (NICU) at the Academic Medical Center (AMC), Amsterdam, The Netherlands. A single nonlinear mixed-effects regression analysis (NONMEM) was performed to describe the population PK of gentamicin. Dosage regimens based upon gestational age (GA) were generated using Monte Carlo simulations with the final model. Target values were based on the MIC distribution in our patient population. In total, 136 gentamicin concentrations from 65 (pre)term neonates were included. The PK was best described by an allometric 2-compartment model with postmenstrual age (PMA) as a covariate on clearance (Cl). The MIC distribution (median, 0.75 [range, 0.5 to 1.5] mg/liter) justified a gentamicin target peak concentration of 8 to 12 mg/liter. This study describes the PK of gentamicin in (pre)term neonates. Dosage regimens of 5 mg/kg of body weight every 48 h, 5 mg/kg every 36 h, and 5 mg/kg every 24 h for patients with GAs of <37 weeks, 37 to 40 weeks, and ≥40 weeks, respectively, are recommended.
authors: Department of Pharmacy, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands y.a.bijleveld@amc.nl.
authors: Yuma A
authors: YA
authors: Bijleveld
authors: Department of Neonatology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: Maria E
authors: ME
authors: van den Heuvel
authors: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: Caspar J
authors: CJ
authors: Hodiamont
authors: Department of Pharmacy, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: Ron A A
authors: RA
authors: Mathôt
authors: Department of Neonatology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: Timo R
authors: TR
authors: de Haan
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005839:Gentamicins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005865:Gestational Age; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000472:pathogenicity*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins
keywords: MIC; gentamicin; neonates; pharmacokinetics