title: High variability in the dosing of commonly used antibiotics revealed by a Europe-wide point prevalence study: implications for research and dissemination.
abstract: BACKGROUND
  Antibiotic dosing in neonates varies between countries and centres, suggesting suboptimal exposures for some neonates. We aimed to describe variations and factors influencing the variability in the dosing of frequently used antibiotics in European NICUs to help define strategies for improvement.
  
  
  METHODS
  A sub-analysis of the European Study of Neonatal Exposure to Excipients point prevalence study was undertaken. Demographic data of neonates receiving any antibiotic on the study day within one of three two-week periods from January to June 2012, the dose, dosing interval and route of administration of each prescription were recorded. The British National Formulary for Children (BNFC) and Neofax were used as reference sources. Risk factors for deviations exceeding ±25% of the relevant BNFC dosage recommendation were identified by multivariate logistic regression analysis.
  
  
  RESULTS
  In 89 NICUs from 21 countries, 586 antibiotic prescriptions for 342 infants were reported. The twelve most frequently used antibiotics - gentamicin, penicillin G, ampicillin, vancomycin, amikacin, cefotaxime, ceftazidime, meropenem, amoxicillin, metronidazole, teicoplanin and flucloxacillin - covered 92% of systemic prescriptions. Glycopeptide class, GA <32 weeks, 5(th) minute Apgar score <5 and geographical region were associated with deviation from the BNFC dosage recommendation. While the doses of penicillins exceeded recommendations, antibiotics with safety concerns followed (gentamicin) or were dosed below (vancomycin) recommendations.
  
  
  CONCLUSIONS
  The current lack of compliance with existing dosing recommendations for neonates needs to be overcome through the conduct of well-designed clinical trials with a limited number of antibiotics to define pharmacokinetics/pharmacodynamics, efficacy and safety in this population and by efficient dissemination of the results.
authors.affiliation: Institute of Microbiology, Tartu University, Tartu, Estonia. Tuuli.Metsvaht@kliinikum.ee.|Clinic of Anaesthesiology and Intensive Care, Tartu University Hospital, Tartu, Estonia. Tuuli.Metsvaht@kliinikum.ee.
authors.forename: Tuuli
authors.initials: T
authors.lastname: Metsvaht
authors.affiliation: Institute of Microbiology, Tartu University, Tartu, Estonia. Georgi.Nellis@kliinikum.ee.|Children's Clinic, Tartu University Hospital, Tartu, Estonia. Georgi.Nellis@kliinikum.ee.
authors.forename: Georgi
authors.initials: G
authors.lastname: Nellis
authors.affiliation: Children's Clinic, Tartu University Hospital, Tartu, Estonia. Heili.Varendi@kliinikum.ee.
authors.forename: Heili
authors.initials: H
authors.lastname: Varendi
authors.affiliation: Alder Hey Children's NHS Foundation Trust, Liverpool, UK. TNunn100@hotmail.com.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Nunn
authors.affiliation: Research and Development, Liverpool women's NHS Foundation Trust, Liverpool, UK. Susan.Graham@lwh.nhs.uk.
authors.forename: Susan
authors.initials: S
authors.lastname: Graham
authors.affiliation: Pharmacy Department, Hospital Antoine Beclère, Paris, France. Andre.Rieutord@abc.aphp.fr.
authors.forename: Andre
authors.initials: A
authors.lastname: Rieutord
authors.affiliation: Pharmacy Department, APHP, Hospital Robert Debré, Paris, France. Thomas.Storme@rdb.aphp.fr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Storme
authors.affiliation: Clinical and Practice Research Group, School of Pharmacy, Queen's University Belfast, Belfast, UK. J.Mcelnay@qub.ac.uk.
authors.forename: James
authors.initials: J
authors.lastname: McElnay
authors.affiliation: Department of Pharmacy, University Hospitals of Leicester, Leicester, UK. Hussain.Mulla@uhl-tr.nhs.uk.
authors.forename: Hussain
authors.initials: H
authors.lastname: Mulla
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, Liverpool Women's NHS Foundation Trust, University of Liverpool, Liverpool, UK. Mark.Turner@liverpool.ac.uk.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Turner
authors.affiliation: Institute of Microbiology, Tartu University, Tartu, Estonia. Irja.Lutsar@ut.ee.
authors.forename: Irja
authors.initials: I
authors.lastname: Lutsar
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001424:Bacterial Infections / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005060:Europe; D019983:Guideline Adherence; D006801:Humans; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D017410:Practice Guidelines as Topic; D010818:Practice Patterns, Physicians'
chemical_list: D000900:Anti-Bacterial Agents