Analytical evaluation of a direct ion-selective-based analyser: Still gaps to close.

Introduction: Discrepancies between electrolyte concentrations determined by blood gas analysers (BGA) and core-lab chemistry analysers may create confusion in clinical practice. This problem is rooted in the different ion-selective electrode (ISE) methodologies that are used. Whilst most available chemistry analysers use indirect ISE, we evaluated the analytical performance of the new automated chemistry analyser Biossays™ E6 (Snibe), equipped with direct ISE, for the determination of sodium (Na), potassium (K), chloride (Cl), ionized calcium (iCa) and pH.

Remote HbA testing via microsampling: fit for purpose?

The collection of capillary blood microsamples via finger-prick has several advantages over traditional blood collection. It is considered convenient and more patient-centric, enabling collection of the sample by the patient at her/his home with subsequent analysis in the lab following postal shipment. Determination of the diabetes biomarker HbA in self-collected microsamples to remotely monitor diabetes patients seems to be a very promising option which could eventually lead to better treatment adaptations and disease control.

Pathogen-based target attainment of optimized continuous infusion dosing regimens of piperacillin-tazobactam and meropenem in surgical ICU patients: a prospective single center observational study.

Background: Several studies have indicated that commonly used piperacillin-tazobactam (TZP) and meropenem (MEM) dosing regimens lead to suboptimal plasma concentrations for a range of pharmacokinetic/pharmacodynamic (PK/PD) targets in intensive care unit (ICU) patients. These targets are often based on a hypothetical worst-case scenario, possibly overestimating the percentage of suboptimal concentrations. We aimed to evaluate the pathogen-based clinically relevant target attainment (CRTA) and therapeutic range attainment (TRA) of optimized continuous infusion dosing regimens of TZP and MEM in surgical ICU patients.

Development and evaluation of uncertainty quantifying machine learning models to predict piperacillin plasma concentrations in critically ill patients.

Background: Beta-lactam antimicrobial concentrations are frequently suboptimal in critically ill patients. Population pharmacokinetic (PopPK) modeling is the golden standard to predict drug concentrations. However, currently available PopPK models often lack predictive accuracy, making them less suited to guide dosing regimen adaptations.

Suboptimal Beta-Lactam Therapy in Critically Ill Children: Risk Factors and Outcome.

Objectives: In critically ill children, severely altered pharmacokinetics may result in subtherapeutic β-lactam antibiotic concentrations when standard pediatric dosing regimens are applied. However, it remains unclear how to recognize patients most at risk for suboptimal exposure and their outcome. This study aimed to: 1) describe target attainment for β-lactam antibiotics in critically ill children, 2) identify risk factors for suboptimal exposure, and 3) study the association between target nonattainment and clinical outcome.

Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors Using Dried Blood Microsamples.

Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) is not yet performed routinely in the standard care of oncology patients, although it offers a high potential to improve treatment outcome and minimize toxicity. TKIs are perfect candidates for TDM as they show a relatively small therapeutic window, a wide inter-patient variability in pharmacokinetics and a correlation between drug concentration and effect. Moreover, most of the available TKIs are susceptible to various drug-drug interactions and medication adherence can be checked by performing TDM.

Automation in Busulfan Therapeutic Drug Monitoring: Evaluation of an Immunoassay on two Routine Chemistry Analyzers.

Background: Therapeutic drug monitoring (TDM) of busulfan is recommended for hematopoietic stem cell transplant recipients. Timely reporting of these TDM results is essential given the short administration period and the planned dose adjustments on day 2. The authors evaluated the performance of a new nanoparticle-based competitive immunoassay on two routine clinical chemistry analyzers and compared its performance to that of an in-house high-resolution mass spectrometry (HRMS) method.

Pilot study of oral fluid and plasma meropenem and piperacillin concentrations in the intensive care unit.

Background: Therapeutic drug monitoring (TDM) of β-lactam antibiotics may be used to optimize dosing for patients in the intensive care unit (ICU). A noninvasive matrix such as oral fluid may be interesting in selected patient groups. We compared the oral fluid concentrations of piperacillin and meropenem with the respective unbound and total concentrations in plasma.

Development and validation of a liquid chromatography high-resolution mass spectrometry orbitrap method for the sensitive quantification of amoxicillin, piperacillin, tazobactam and meropenem in human faeces.

Beta-lactam antibiotics are of vital importance for the treatment of infections in a broad range of patients. Although most systemically administered antibiotics will be excreted renally, a fraction will reach the gastro-intestinal tract, affecting the intestinal microbiome by eradicating a wide range of bacterial species while facilitating the growth of antimicrobial-resistant species. A better understanding of the kinetics of beta-lactam antibiotics in the gastro-intestinal tract is essential to study their role in the development of antibiotic resistance in bacteria and to help develop future therapies to prevent damage to, or restore, the intestinal microbiome.

Quantification of eight hematological tyrosine kinase inhibitors in both plasma and whole blood by a validated LC-MS/MS method.

Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. Therefore, a high-throughput, sensitive LC-MS/MS method was developed and validated, to be used for personalized treatment of hematologic malignancies. The assay allows the simultaneous quantification in plasma (EDTA and heparin) and whole blood of eight TKIs, including bosutinib, dasatinib, gilteritinib, ibrutinib, imatinib, midostaurin, nilotinib and ponatinib, which are used in the treatment of chronic and acute myeloid leukemia (CML, AML) and chronic lymphocytic leukemia (CLL).

Prolonged Versus Intermittent Infusion of β-Lactam Antibiotics: A Systematic Review and Meta-Regression of Bacterial Killing in Preclinical Infection Models.

Background: Administering β-lactam antibiotics via prolonged infusions for critically ill patients is mainly based on preclinical evidence. Preclinical data on this topic have not been systematically reviewed before.

Objectives: The aim of this study was to describe the pharmacokinetic/pharmacodynamic (PK/PD) indices and targets reported in preclinical models and to compare the bactericidal efficacy of intermittent and prolonged infusions of β-lactam antibiotics.

Subtherapeutic piperacillin concentrations in neurocritical patients.

Purpose: Increased renal elimination is the leading cause for subtherapeutic concentrations of renally cleared antibiotics and it has been hypothesized that brain damaged patients in the intensive care unit (ICU) are particularly at risk. The objective of this study is to determine the prevalence of subtherapeutic piperacillin concentrations in neurocritical patients and to investigate if having a neurocritical diagnosis is a risk factor for this.

Materials And Methods: Single center retrospective analysis of a prospective cohort study of adult ICU patients receiving continuous infusion piperacillin/tazobactam.

Early target attainment of continuous infusion piperacillin/tazobactam and meropenem in critically ill patients: A prospective observational study.

Purpose: To evaluate target attainment of empirically dosed continuous infusion piperacillin/tazobactam (TZP) and meropenem (MER) in critically ill patients.

Patients And Methods: Patients were sampled on a daily basis. TZP or MER concentrations were evaluated during the first two days antibiotic therapy.

Measuring Unbound Versus Total Piperacillin Concentrations in Plasma of Critically Ill Patients: Methodological Issues and Relevance.

Background: Piperacillin is considered a moderately protein-bound antibiotic (20%-40%), with albumin being an important binding protein. Although infrequently used in practice, different methods to measure the fraction unbound (fu) are available, but uncertainty remains as to what the most appropriate method is. The main goal of this study was to estimate the impact of the methodology used to measure unbound piperacillin in plasma on the fu of piperacillin; we compared ultrafiltration (UF) at 4°C and 37°C with the reference method, equilibrium dialysis.

Population pharmacokinetics and evaluation of the predictive performance of pharmacokinetic models in critically ill patients receiving continuous infusion meropenem: a comparison of eight pharmacokinetic models.

Background: Several population pharmacokinetic (PopPK) models for meropenem dosing in ICU patients are available. It is not known to what extent these models can predict meropenem concentrations in an independent validation dataset when meropenem is infused continuously.

Patients And Methods: A PopPK model was developed with concentration-time data collected from routine care of 21 ICU patients (38 samples) receiving continuous infusion meropenem.