title: Uncertainty in Antibiotic Dosing in Critically Ill Neonate and Pediatric Patients: Can Microsampling Provide the Answers?
abstract: With a decreasing supply of antibiotics that are effective against the pathogens that cause sepsis, it is critical that we learn to use currently available antibiotics optimally. Pharmacokinetic studies provide an evidence base from which we can optimize antibiotic dosing. However, these studies are challenging in critically ill neonate and pediatric patients due to the small blood volumes and associated risks and burden to the patient from taking blood. We investigate whether microsampling, that is, obtaining a biologic sample of low volume (<50 μL), can improve opportunities to conduct pharmacokinetic studies.
  
  
  
  We performed a literature search to find relevant articles using the following search terms: sepsis, critically ill, severe infection, intensive care AND antibiotic, pharmacokinetic, p(a)ediatric, neonate. For microsampling, we performed a search using antibiotics AND dried blood spots OR dried plasma spots OR volumetric absorptive microsampling OR solid-phase microextraction OR capillary microsampling OR microsampling. Databases searched include Web of Knowledge, PubMed, and EMbase.
  
  
  
  Of the 32 antibiotic pharmacokinetic studies performed on critically ill neonate or pediatric patients in this review, most of the authors identified changes to the pharmacokinetic properties in their patient group and recommended either further investigations into this patient population or therapeutic drug monitoring to ensure antibiotic doses are suitable. There remain considerable gaps in knowledge regarding the pharmacokinetic properties of antibiotics in critically ill pediatric patients. Implementing microsampling in an antibiotic pharmacokinetic study is contingent on the properties of the antibiotic, the pathophysiology of the patient (and how this can affect the microsample), and the location of the patient. A validation of the sampling technique is required before implementation.
  
  
  
  Current antibiotic regimens for critically ill neonate and pediatric patients are frequently suboptimal due to a poor understanding of altered pharmacokinetic properties. An assessment of the suitability of microsampling for pharmacokinetic studies in neonate and pediatric patients is recommended before wider use. The method of sampling, as well as the method of bioanalysis, also requires validation to ensure the data obtained reflect the true result.
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia; Paediatric Intensive Care, Lady Cilento Children's Hospital, Brisbane, Australia.
authors.forename: Tavey
authors.initials: T
authors.lastname: Dorofaeff
authors.affiliation: School of Physiology, University of the Witwatersrand, Johannesburg, South Africa; Wits UQ Critical Care Infection Collaboration, Johannesburg, South Africa.
authors.forename: Rossella M
authors.initials: RM
authors.lastname: Bandini
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia; Wits UQ Critical Care Infection Collaboration, Johannesburg, South Africa; Department of Intensive Care Medicine, Royal Brisbane Hospital, Brisbane, Australia; Faculty of Health, Brisbane, Queensland University of Technology, Brisbane, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Wits UQ Critical Care Infection Collaboration, Johannesburg, South Africa; Department of Paediatrics and Child Health, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Daynia E
authors.initials: DE
authors.lastname: Ballot
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia; Department of Intensive Care Medicine, Royal Brisbane Hospital, Brisbane, Australia; Department of Pharmacy, Royal Brisbane Hospital, Brisbane, Australia; School of Pharmacy, The University of Queensland, Brisbane, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia. Electronic address: suzanne.parker@uq.edu.au.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Parker
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D001800:Blood Specimen Collection / Q000379:methods; D016638:Critical Illness / Q000628:therapy*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D018805:Sepsis / Q000097:blood / Q000188:drug therapy; D035501:Uncertainty
chemical_list: D000900:Anti-Bacterial Agents
keywords: antibiotic; microsampling; pharmacokinetic