Validation of a Dried Blood Spot Ceftriaxone Assay in Papua New Guinean Children with Severe Bacterial Infections.

Autor: Mukap M; School of Medicine, University of Papua New Guinea, Port Moresby, Papua New Guinea.; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea., Sprod C; School of Medicine, University of Papua New Guinea, Port Moresby, Papua New Guinea.; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea., Tefuarani N; School of Medicine, University of Papua New Guinea, Port Moresby, Papua New Guinea., Laman M; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea., Page-Sharp M; School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, Western Australia, Australia., Salman S; Medical School, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia., Moore BR; School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, Western Australia, Australia.; Medical School, University of Western Australia, Harry Perkins Research Institute, Fiona Stanley Hospital, Murdoch, Western Australia, Australia., Batty KT; School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, Western Australia, Australia., Davis TME; Department of Medicine, Fremantle Hospital, Fremantle, Western Australia, Australia.; Medical School, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia., Manning L; Medical School, University of Western Australia, Harry Perkins Research Institute, Fiona Stanley Hospital, Murdoch, Western Australia, Australia laurens.manning@uwa.edu.au.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2018 Sep 24; Vol. 62 (10). Date of Electronic Publication: 2018 Sep 24 (Print Publication: 2018).
DOI: 10.1128/AAC.00940-18
Abstrakt: Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK) studies in situations where venous blood sampling is logistically and/or ethically challenging. In this study, we aimed to demonstrate the validity of a DBS ceftriaxone assay in a PK study of children with severe illness from Papua New Guinea (PNG), a setting in which health care resources are limited and anemia is common. Using a previously validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, serial plasma and DBS ceftriaxone concentrations were measured in PNG children aged 5 to 10 years with acute bacterial meningitis or severe pneumonia. The concentration-time data were incorporated into population PK models. Ten children were recruited with an admission hematocrit of 0.22 to 0.52. Raw data demonstrated good correlation between plasma and DBS concentrations (Spearman's rank correlation coefficient [ r s ] = 0.94 [95% confidence interval, 0.91 to 0.97], P < 0.0001). A marked systematic hematocrit bias was observed, with lower hematocrits resulting in underestimation of DBS-predicted plasma concentration. After adjustment for red cell partitioning and hematocrit bias, a population PK model comparing plasma and DBS-predicted plasma concentrations did not differ in terms of key PK parameters, including clearance, volume of distribution, and residual variability. The performance of the ceftriaxone DBS assay is robust and provides reassurance that this platform can be used as a surrogate for plasma concentrations to provide valid PK and PK/pharmacodynamic studies of severely unwell children hospitalized in a resource-limited setting. It highlights the importance of hematocrit bias in validation studies of DBS assays.
(Copyright © 2018 American Society for Microbiology.)
Databáze: MEDLINE
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