A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.

Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.

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.

Oral Anticoagulation in Patients With Advanced Chronic Kidney Disease and Atrial Fibrillation: Beyond Anticoagulation.

The optimal approach to prevent stroke and systemic embolism in patients with advanced chronic kidney disease (CKD) and atrial fibrillation remains unresolved. We conducted a narrative review to explore areas of uncertainty and opportunities for future research. First, the relationship between atrial fibrillation and stroke is more complex in patients with advanced CKD than in the general population.

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.

Why We May Need Higher Doses of Beta-Lactam Antibiotics: Introducing the 'Maximum Tolerable Dose'.

The surge in antimicrobial resistance and the limited availability of new antimicrobial drugs has fueled the interest in optimizing antibiotic dosing. An ideal dosing regimen leads to maximal bacterial cell kill, whilst minimizing the risk of toxicity or antimicrobial resistance. For beta-lactam antibiotics specifically, PK/PD-based considerations have led to the widespread adoption of prolonged infusion.

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.

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.

Therapeutic drug monitoring of β-lactam antibiotics in the ICU.

Introduction: Individualizing antibiotic therapy is paramount to improve clinical outcomes while minimizing the risk of toxicity and antimicrobial therapy. β-lactam antibiotics are amongst the drugs most commonly prescribed in the Intensive Care Unit (ICU). The pharmacokinetics of β-lactam antibiotics are profoundly altered in critically ill patients, leading to the failure of standard drug dosing regimens to result in adequate drug concentrations.

Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study.

Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation.

Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3 days of therapy.

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.

Antibiotic stewardship in sepsis management: toward a balanced use of antibiotics for the severely ill patient.

Severe infections in critically ill patients carry a high morbidity and mortality rate. Given the impact of early and broad-spectrum empirical therapy in several studies and the emphasis on this in international guidelines, there is a low threshold for initiating antibiotics in many patients with suspected infection. This has led to the widespread use of antibiotics in critically ill patients, which is often unnecessary or inappropriate.

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.

Emergence of antimicrobial resistance to piperacillin/tazobactam or meropenem in the ICU: Intermittent versus continuous infusion. A retrospective cohort study.

Background: Prolonged infusion of beta-lactam antibiotics is broadly recognized as a strategy to optimize antibiotic therapy by achieving a higher percentage of time that concentrations remain above the minimal inhibitory concentration (% fT), i.e. the pharmacokinetic/pharmacodynamic (PK/PD) index.

Population pharmacokinetics of continuous infusion of piperacillin in critically ill patients.

Dosing recommendations for continuous infusion of piperacillin, a broad-spectrum beta-lactam antibiotic, are mainly guided by outputs from population pharmacokinetic models constructed with intermittent infusion data. However, the probability of target attainment in patients receiving piperacillin by continuous infusion may be overestimated when drug clearance estimates from population pharmacokinetic models based on intermittent infusion data are used, especially when higher doses (e.g.

Student participation: to the benefit of both the student and the faculty.

Students who actively participate in the evaluation of their undergraduate medical curriculum become important stakeholders in decisions related to the design of the school's curriculum. Research and reports on student participation in curriculum change are scarce, and not much is known about how students personally benefit. We describe the structure and activities of engaging students in designing and improving the curriculum at the Faculty of Medicine and Health Sciences of Ghent University (Belgium).

Gouty arthritis of the spine in a renal transplant patient: a clinical case report: an unusual presentation of a common disorder.

Axial gout is a well-documented but uncommon manifestation of gout. Its mimicking nature and the impracticality of axial joint aspiration might considerably delay its diagnosis. We report a case in a normouricemic renal transplant recipient, whereby the primary symptom of severe neck pain suggested pyogenic spondylodiscitis as an initial tentative diagnosis.