Microdialysis sampling to monitor target-site vancomycin concentrations in septic infants: a feasible way to close the knowledge gap

Schroepf, Sebastian; Burau, Daniela; Muench, Hans-Georg; Derendorf, Hartmut; Zeitlinger, Markus; Genzel‐Boroviczény, Orsolya; Adam, Dieter; Kloft, Charlotte

doi:10.1016/j.ijantimicag.2021.106405

Cited by 7 publications

(3 citation statements)

References 36 publications

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“…All these factors may affect the precision of the obtained concentrations. For intravenous microdialysis sampling, it has been recommended to apply a flow rate of 0.3 μL/min and a membrane length of 30 mm to increase relative recovery [ 6 , 7 , 19 , 26 ]. In microdialysis studies, it is generally recognized that an acceptable trade-off between the ideal setup and the experimental requirements is unavoidable.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Intravenous Microdialysis and Standard Plasma Sampling for Monitoring of Vancomycin and Meropenem Plasma Concentrations—An Experimental Porcine Study

et al. 2023

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Microdialysis is a catheter-based method suitable for dynamic sampling of unbound antibiotic concentrations. Intravenous antibiotic concentration sampling by microdialysis has several advantages and may be a superior alternative to standard plasma sampling. We aimed to compare concentrations obtained by continuous intravenous microdialysis sampling and by standard plasma sampling of both vancomycin and meropenem in a porcine model. Eight female pigs received 1 g of both vancomycin and meropenem, simultaneously over 100 and 10 min, respectively. Prior to drug infusion, an intravenous microdialysis catheter was placed in the subclavian vein. Microdialysates were collected for 8 h. From a central venous catheter, plasma samples were collected in the middle of every dialysate sampling interval. A higher area under the concentration/time curve and peak drug concentration were found in standard plasma samples compared to intravenous microdialysis samples, for both vancomycin and meropenem. Both vancomycin and meropenem concentrations obtained with intravenous microdialysis were generally lower than from standard plasma sampling. The differences in key pharmacokinetic parameters between the two sampling techniques underline the importance of further investigations to find the most suitable and reliable method for continuous intravenous antibiotic concentration sampling.

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Section: Discussionmentioning

confidence: 99%

Comparison of Intravenous Microdialysis and Standard Plasma Sampling for Monitoring of Vancomycin and Meropenem Plasma Concentrations—An Experimental Porcine Study

et al. 2023

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“…Schroepf et al have recently published a MD study with vancomycin in which they included experiments with different flow rates in the in vitro setting. They demonstrated an increase in recovery from 27.1 to 51.1% by decreasing the flow rate from 2 to 0.5 µL/min [ 22 ]. However, the minimum volume required for sample analysis has to be taken into account when reducing the flow rate to such low values.…”

Section: Discussionmentioning

confidence: 99%

Pilot Pharmacokinetic Study in Healthy Adults Using Intravascular Microdialysis Catheters Modified for Use in Paediatric Patients to Assess Vancomycin Blood Levels

et al. 2022

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Background and Objective Exhaustive pharmacokinetic (PK) studies in paediatric patients are unavailable for most antibiotics and feasibility of PK studies is limited by challenges, such as low blood volume and venipuncture-related pain. Microdialysis (MD) represents a promising method to overcome these obstacles. The aim of this proof-of-concept study was to develop and validate modified MD catheters that can be used to obtain concentration-time profiles of antibiotics in paediatric patients. Methods Following extensive in vitro MD experiments, a prospective open-labelled study in ten healthy adult volunteers (HVs) was conducted. Subjects received a single intravenous dose of 1000 mg vancomycin, then plasma and intravascular microdialysate were sampled over 24 h. In vivo MD probe calibration was conducted using the retrodialysis technique. Plasma protein binding was measured using ultrafiltration. Confirmation of the measurements was performed using a Bland-Altman plot, relevant PK parameters were calculated, and a pharmacometric model was established. Results No safety issues were encountered. The concentration-time curves of microdialysate and plasma measurements showed good alignment. The Bland-Altman plot yielded a mean bias of 0.19 mg/L and 95% limits of agreement of − 9.34 to 9.71 mg/L. A two-compartment model best described plasma PK, model-based estimates for recovery of the MD probes being in high agreement with the observed values. Quantified estimates of fraction unbound were comparable between plasma and microdialysate (p = 0.56). Conclusions An innovative MD catheter that can be inserted into small intravenous lines was successfully developed and applied in HV. This proof-of-concept study is encouraging and opens the way to further experiments leading towards future use of MD in paediatric patients.

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“…This results in intra- and interpatient variability in antibiotic concentration at the site of infection [ 7 , 8 ]. A wide range of methods might be used to assess penetration at the target site in critically ill patients [ 178 , 179 ], although they cannot be used routinely. Instead, we could strengthen antibiotic dosing strategies with biomarkers that correlate with pharmacokinetic alterations, since they might predict target-site concentrations (Fig.…”

Section: Biomarker-guided Dosingmentioning

confidence: 99%

Biomarkers Predicting Tissue Pharmacokinetics of Antimicrobials in Sepsis: A Review

Codina

Jorda

2022

Clin Pharmacokinet

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The pathophysiology of sepsis alters drug pharmacokinetics, resulting in inadequate drug exposure and target-site concentration. Suboptimal exposure leads to treatment failure and the development of antimicrobial resistance. Therefore, we seek to optimize antimicrobial therapy in sepsis by selecting the right drug and the correct dosage. A prerequisite for achieving this goal is characterization and understanding of the mechanisms of pharmacokinetic alterations. However, most infections take place not in blood but in different body compartments. Since tissue pharmacokinetic assessment is not feasible in daily practice, we need to tailor antibiotic treatment according to the specific patient's pathophysiological processes. The complex pathophysiology of sepsis and the ineffectiveness of current targeted therapies suggest that treatments guided by biomarkers predicting target-site concentration could provide a new therapeutic strategy. Inflammation, endothelial and coagulation activation markers, and blood flow parameters might be indicators of impaired tissue distribution. Moreover, hepatic and renal dysfunction biomarkers can predict not only drug metabolism and clearance but also drug distribution. Identification of the right biomarkers can direct drug dosing and provide timely feedback on its effectiveness. Therefore, this might decrease antibiotic resistance and the mortality of critically ill patients. This article fills the literature gap by characterizing patient biomarkers that might be used to predict unbound plasma-to-tissue drug distribution in critically ill patients. Although all biomarkers must be clinically evaluated with the ultimate goal of combining them in a clinically feasible scoring system, we support the concept that the appropriate biomarkers could be used to direct targeted antibiotic dosing.

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Microdialysis sampling to monitor target-site vancomycin concentrations in septic infants: a feasible way to close the knowledge gap

Cited by 7 publications

References 36 publications

Comparison of Intravenous Microdialysis and Standard Plasma Sampling for Monitoring of Vancomycin and Meropenem Plasma Concentrations—An Experimental Porcine Study

Comparison of Intravenous Microdialysis and Standard Plasma Sampling for Monitoring of Vancomycin and Meropenem Plasma Concentrations—An Experimental Porcine Study

Pilot Pharmacokinetic Study in Healthy Adults Using Intravascular Microdialysis Catheters Modified for Use in Paediatric Patients to Assess Vancomycin Blood Levels

Biomarkers Predicting Tissue Pharmacokinetics of Antimicrobials in Sepsis: A Review

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