Ceftazidime-avibactam (CAZ-AVI) pharmacokinetics in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF).

Purpose: To investigate the pharmacokinetics (PK) of ceftazidime-avibactam (CAZ-AVI) in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF), and compare with a general phase III trial population.

Methods: A prospective PK study was conducted in critically ill patients who received CVVHDF for acute kidney injury, treated with CAZ-AVI (1000/250 mg or 2000/500 mg q8h). Plasma and CVVHDF-circuit samples were collected to determine CAZ-AVI concentrations.

PK/PD modelling and simulation of longitudinal meropenem in vivo effects against Escherichia coli and Klebsiella pneumoniae strains with high MICs.

Background: Carbapenem-resistant bacteria pose a threat to public health. Characterising the pharmacokinetics-pharmacodynamics (PKPD) of meropenem longitudinally in vivo against resistant bacteria could provide valuable information for development and translation of carbapenem-based therapies.

Objectives: To assess the time course of meropenem effects in vivo against strains with high MIC to predict PK/PD indices and expected efficacy in patients using a modelling approach.

Model-informed precision dosing of vancomycin in clinical practice: an intervention development study.

Background: Current guidelines recommend dosing vancomycin based on the area under the concentration time curve (AUC) to maximise efficacy and minimise the risk of nephrotoxicity. The preferred approach to AUC-guided therapy is to apply model-informed precision dosing (MIPD). However, the adoption in clinical practice has been slow.

'You're Just Thinking About Going Home': Exploring Person-Centred Medication Communication With Older Patients at Hospital Discharge.

Background: The hospital discharge process poses significant safety risks for older patients due to complexities in communication and coordination among stakeholders, leading to potential drug-related problems post-discharge. Adopting a person-centred care (PCC) approach in medication communication by healthcare professionals (HCPs) is crucial to ensure positive health outcomes. This study aimed to explore the practice of PCC in medication communication between older patients and HCPs during the hospital discharge process.

Physiologically-based pharmacokinetic modelling in sepsis: A tool to elucidate how pathophysiology affects meropenem pharmacokinetics.

Objectives: Applying physiologically-based pharmacokinetic (PBPK) modelling in sepsis could help to better understand how PK changes are influenced by drug- and patient-related factors. We aimed to elucidate the influence of sepsis pathophysiology on the PK of meropenem by applying PBPK modelling.

Methods: A whole-body meropenem PBPK model was developed and evaluated in healthy individuals, and renally impaired non-septic patients.

Model-based translation of results from in vitro to in vivo experiments for afabicin activity against Staphylococcus aureus.

Background: Translation of experimental data on antibiotic activity typically relies on pharmacokinetic/pharmacodynamic (PK/PD) indices. Model-based approaches, considering the full antibiotic killing time course, could be an alternative.

Objectives: To develop a mechanism-based modelling framework to assess the in vitro and in vivo activity of the FabI inhibitor antibiotic afabicin, and explore the ability of a model built on in vitro data to predict in vivo outcome.

Quantifying combined effects of colistin and ciprofloxacin against Escherichia coli in an in silico pharmacokinetic-pharmacodynamic model.

Co-administering a low dose of colistin (CST) with ciprofloxacin (CIP) may improve the antibacterial effect against resistant Escherichia coli, offering an acceptable benefit-risk balance. This study aimed to quantify the interaction between ciprofloxacin and colistin in an in silico pharmacokinetic-pharmacodynamic model from in vitro static time-kill experiments (using strains with minimum inhibitory concentrations, MIC 0.023-1 mg/L and MIC 0.

Estimated glomerular filtration rate as a tool for early identification of patients with insufficient exposure to beta-lactam antibiotics in intensive care units.

Background: Only about 50% of intensive care unit (ICU) patients reach a free trough concentration above MIC (100% fT > MIC) of beta-lactam antibiotics. Although dose adjustments based on therapeutic drug monitoring (TDM) could be beneficial, TDM is not widely available. We investigated serum creatinine-based estimated GFR (eGFR) as a rapid screening tool to identify ICU patients at risk of insufficient exposure.

Therapeutic drug monitoring of monoclonal antibodies in chronic inflammatory diseases: A snapshot of laboratories and applications across Europe.

The European Cooperation in Science and Technology (COST) action ENOTTA (The European Network on Optimising Treatment with Therapeutic Antibodies in chronic inflammatory diseases) was launched in 2022. To pave the way for harmonization of analytical methods for quantitation of serum levels of therapeutic antibodies in research and clinical settings, ENOTTA recently performed an online survey mapping laboratories in the field. The survey, which contained 30 questions surrounding therapeutic drug monitoring of relevant drugs and anti-drug antibodies, was distributed via the ENOTTA and European Federation of Clinical Chemistry and Laboratory networks.

Synergy of polymyxin B and minocycline against KPC-3- and OXA-48-producing Klebsiella pneumoniae in dynamic time-kill experiments: agreement with in silico predictions.

Objectives: Combination therapy is often used for carbapenem-resistant Gram-negative bacteria. We previously demonstrated synergy of polymyxin B and minocycline against carbapenem-resistant Klebsiella pneumoniae in static time-kill experiments and developed an in silico pharmacokinetic/pharmacodynamic (PK/PD) model. The present study assessed the synergistic potential of this antibiotic combination in dynamic experiments.

Therapeutic drug monitoring of vancomycin and meropenem: Illustration of the impact of inaccurate information in dose administration time.

Objectives: To illustrate the impact of errors in documented dose administration time on therapeutic drug monitoring (TDM)-based target attainment evaluation for vancomycin and meropenem, and to explore the influence of drug and patient characteristics, and TDM sampling strategies.

Methods: Bedside observations of errors in documented dose administration times were collected. Population pharmacokinetic simulations were performed for vancomycin and meropenem, evaluating different one- and two-sampling strategies for populations with estimated creatinine clearance (CLcr) of 30, 80 or 130 mL/min.

The complexities of communication at hospital discharge of older patients: a qualitative study of healthcare professionals' views.

Background: Hospital discharge of older patients is a high-risk situation in terms of patient safety. Due to the fragmentation of the healthcare system, communication and coordination between stakeholders are required at discharge. The aim of this study was to explore communication in general and medication information transfer in particular at hospital discharge of older patients from the perspective of healthcare professionals (HCPs) across different organisations within the healthcare system.

Model-based assessment of neutrophil-mediated phagocytosis and digestion of bacteria across in vitro and in vivo studies.

Neutrophil granulocytes are key components of the host response against pathogens, and severe neutropenia, with neutrophil counts below 0.5 × 10 cells/mL, renders patients increasingly vulnerable to infections. Published in vitro (n = 7) and in vivo (n = 5) studies with time-course information on bacterial and neutrophil counts were digitized to characterize the kinetics of neutrophil-mediated bacterial killing and inform on the immune systems' contribution to the clearance of bacterial infections.

Predicting cytokine kinetics during sepsis; a modelling framework from a porcine sepsis model with live Escherichia coli.

Background: Describing the kinetics of cytokines involved as biomarkers of sepsis progression could help to optimise interventions in septic patients. This work aimed to quantitively characterise the cytokine kinetics upon exposure to live E. coli by developing an in silico model, and to explore predicted cytokine kinetics at different bacterial exposure scenarios.

Risk factors for and preventability of drug-related hospital revisits in older patients: A post-hoc analysis of a randomized clinical trial.

Aim: The aims of this study were (1) to identify older patients' risk factors for drug-related readmissions and (2) to assess the preventability of older patients' drug-related revisits.

Methods: Post hoc analysis of a randomized clinical trial with patients aged ≥65 years at eight wards within four hospitals in Sweden. (1) The primary outcome was risk factors for drug-related readmission within 12 months post-discharge.

Research priorities towards precision antibiotic therapy to improve patient care.

Antibiotic resistance presents an incessant threat to our drug armamentarium that necessitates novel approaches to therapy. Over the past several decades, investigation of pharmacokinetic and pharmacodynamic (PKPD) principles has substantially improved our understanding of the relationships between the antibiotic, pathogen, and infected patient. However, crucial gaps in our understanding of the pharmacology of antibacterials and their optimal use in the care of patients continue to exist; simply attaining antibiotic exposures that are considered adequate based on traditional targets can still result in treatment being unsuccessful and resistance proliferation for some infections.

Changes in critical inhaler technique errors in inhaled COPD treatment - A one-year follow-up study in Sweden.

Background: Critical inhaler technique errors have been associated with lower treatment efficacy in chronic obstructive pulmonary disease (COPD). We aimed to assess and follow-up critical inhaler technique errors, and to investigate their association with COPD symptoms and exacerbations.

Methods: COPD-diagnosed primary and secondary care outpatients (n = 310) demonstrated inhaler technique with inhaler devices they were currently using.

Continuous infusion of piperacillin-tazobactam significantly improves target attainment in children with cancer and fever.

Background: Children with febrile neutropenia commonly exhibit alterations of pharmacokinetic (PK) parameters, leading to decreased β-lactam concentrations.

Aims: This study evaluated piperacillin PK and probability of target attainment (PTA) with continuous infusion of piperacillin-tazobactam, in order to optimize the dosing regimen.

Methods: This prospective PK study included children with cancer, aged 1-17 years, who were treated with piperacillin-tazobactam for suspected or verified infection.

Population pharmacokinetics of cefotaxime in intensive care patients.

Purpose: To characterise the pharmacokinetics and associated variability of cefotaxime in adult intensive care unit (ICU) patients and to assess the impact of patient covariates.

Methods: This work was based on data from cefotaxime-treated patients included in the ACCIS (Antibiotic Concentrations in Critical Ill ICU Patients in Sweden) study. Clinical data from 51 patients at seven different ICUs in Sweden, given cefotaxime (1000-3000 mg given 2-6 times daily), were collected from the first day of treatment for up to three consecutive days.

Effects of Hospital-Based Comprehensive Medication Reviews Including Postdischarge Follow-up on Older Patients' Use of Health Care: A Cluster Randomized Clinical Trial.

Importance: Suboptimal use of medications is a leading cause of health care-related harm. Medication reviews improve medication use, but evidence of the possible benefit of inpatient medication review for hard clinical outcomes after discharge is scarce.

Objective: To study the effects of hospital-based comprehensive medication reviews (CMRs), including postdischarge follow-up of older patients' use of health care resources, compared with only hospital-based reviews and usual care.