Uncertainty in antibiotic dosing in critically ill neonate and pediatric patients: can microsampling provide the answers?

Dorofaeff, Tavey, Bandini, Rossella M., Lipman, Jeffrey, Ballot, Daynia E., Roberts, Jason A. and Parker, Suzanne L. (2016) Uncertainty in antibiotic dosing in critically ill neonate and pediatric patients: can microsampling provide the answers?. Clinical Therapeutics, 38 9: 1961-1975. doi:10.1016/j.clinthera.2016.07.093


Author Dorofaeff, Tavey
Bandini, Rossella M.
Lipman, Jeffrey
Ballot, Daynia E.
Roberts, Jason A.
Parker, Suzanne L.
Title Uncertainty in antibiotic dosing in critically ill neonate and pediatric patients: can microsampling provide the answers?
Journal name Clinical Therapeutics   Check publisher's open access policy
ISSN 1879-114X
0149-2918
Publication date 2016-09-01
Year available 2016
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.clinthera.2016.07.093
Open Access Status Not yet assessed
Volume 38
Issue 9
Start page 1961
End page 1975
Total pages 15
Place of publication New York, NY, United States
Publisher Elsevier
Language eng
Abstract Purpose: 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 mu L), can improve opportunities to conduct pharmacokinetic studies.
Formatted abstract
Purpose: 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.

Methods: 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.

Findings: 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.

Implications: 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.
Keyword Antibiotic
Microsampling
Pharmacokinetic
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1048652
APP1044941
APP1099452
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: UQ Centre for Clinical Research Publications
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