Is there a role for microsampling in antibiotic pharmacokinetic studies?

Parker, Suzanne L.; Dorofaeff, Tavey; Lipman, Jeffrey; Ballot, Daynia; Bandini, Rossella M.; Wallis, Steven C.; Roberts, Jason A.

doi:10.1080/17425255.2016.1178238

Cited by 23 publications

(22 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Validation of novel methods for the monitoring and dose optimization of antimicrobial agents is required. Whilst several studies have explored the role of microfluidics, 22 , 23 , 25 these are still hindered by many of the problems associated with routine antimicrobial TDM strategies, such as the need for laboratory analysis and transport of blood products. One potential method for avoiding these problems is the development of closed-loop systems based on minimally invasive, microneedle electrochemical sensor technology.…”

Section: Introductionmentioning

confidence: 99%

Delivering precision antimicrobial therapy through closed-loop control systems

Rawson

O’Hare

Herrero

et al. 2017

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients.

show abstract

Section: Introductionmentioning

confidence: 99%

Delivering precision antimicrobial therapy through closed-loop control systems

Rawson

O’Hare

Herrero

et al. 2017

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

show abstract

“…Despite emerging scientific interest in microsampling, there is limited industry or regulatory guidance to inform the approaches to validation of DBS bioanalytical assays for use in regulatory studies (6,14). The FDA draft guideline from 2013 specifies that storage and handling, thermal stability, homogeneity of spotting, hematocrit, carryover, and reproducibility should be considered minimum requirements.…”

Section: Discussionmentioning

confidence: 99%

“…The measurement of drug concentrations in dried blood spots (DBS) collected on filter paper represents a promising way of resolving these issues, particularly where there are none of the laboratory facilities required to process, store, and transport blood or plasma samples (6). In a previous study from our group, we developed and validated a DBS ceftriaxone assay using healthy adult Australians.…”

mentioning

confidence: 99%

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

Mukap

Sprod

Tefuarani

et al. 2018

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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 [] = 0.94 [95% confidence interval, 0.91 to 0.97], < 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.

show abstract

“…Decisions for using microsampling in a pharmacokinetic study can be based on a "contingency approach," as described by Parker et al 27 This approach considers the impact of the properties of the antibiotic, as well as the type and geographical location of the patients.…”

Section: Considerations For Study Design Using Microsamplingmentioning

confidence: 99%

“…[21][22][23]26 Innovation in the quantitative analysis of clinical samples, led by improved sensitivity of analytical methods, has reduced blood sample volumes to "microsamples." 27 Microsampling uses a low volume of sample (o50 μL), with some acquired by skin prick. Microsamples can require frozen storage or be dried for transport and storage.…”

Section: Introductionmentioning

confidence: 99%