Tavey Dorofaeff1, Rossella M Bandini2, Jeffrey Lipman3, Daynia E Ballot4, Jason A Roberts5, Suzanne L Parker6. 1. Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia; Paediatric Intensive Care, Lady Cilento Children's Hospital, Brisbane, Australia. 2. School of Physiology, University of the Witwatersrand, Johannesburg, South Africa; Wits UQ Critical Care Infection Collaboration, Johannesburg, South Africa. 3. 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. 4. Wits UQ Critical Care Infection Collaboration, Johannesburg, South Africa; Department of Paediatrics and Child Health, University of the Witwatersrand, Johannesburg, South Africa. 5. 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. 6. Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia. Electronic address: suzanne.parker@uq.edu.au.
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.
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.
Authors: Yarmarly C Guerra Valero; Tavey Dorofaeff; Jason A Roberts; Jeffrey Lipman; Mark G Coulthard; Louise Sparkes; Steven C Wallis; Suzanne L Parker Journal: Anal Bioanal Chem Date: 2021-05-26 Impact factor: 4.142
Authors: Cinzia Auriti; Bianca Maria Goffredo; Maria Paola Ronchetti; Fiammetta Piersigilli; Sara Cairoli; Iliana Bersani; Andrea Dotta; Manjunath P Pai Journal: Antimicrob Agents Chemother Date: 2018-09-24 Impact factor: 5.191
Authors: Craig R Rayner; Patrick F Smith; David Andes; Kayla Andrews; Hartmut Derendorf; Lena E Friberg; Debra Hanna; Alex Lepak; Edward Mills; Thomas M Polasek; Jason A Roberts; Virna Schuck; Mark J Shelton; David Wesche; Karen Rowland-Yeo Journal: Clin Pharmacol Ther Date: 2021-03-09 Impact factor: 6.875
Authors: Yarmarly C Guerra Valero; Tavey Dorofaeff; Mark G Coulthard; Louise Sparkes; Jeffrey Lipman; Steven C Wallis; Jason A Roberts; Suzanne L Parker Journal: J Antimicrob Chemother Date: 2022-07-28 Impact factor: 5.758
Authors: Jennifer Le; Brenda Poindexter; Janice E Sullivan; Matthew Laughon; Paula Delmore; Martha Blackford; Ram Yogev; Laura P James; Chiara Melloni; Barrie Harper; Jeff Mitchell; Daniel K Benjamin; Felix Boakye-Agyeman; Michael Cohen-Wolkowiez Journal: Ther Drug Monit Date: 2018-02 Impact factor: 3.118