ArticleThe Journal of antimicrobial chemotherapy2020
Optimization of flucloxacillin dosing regimens in critically ill patients using population pharmacokinetic modelling of total and unbound concentrations.
Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review.Frontiers in pharmacology · 2022Pooled it
- Predictive performance of an antibiotic precision dosing software program in critically ill adults with infection.The Journal of antimicrobial chemotherapy · 2026Article
- Type 2 diabetes mellitus as a state of altered drug pharmacokinetic-pharmacodynamic parameters: an update on recent developments and clinical implications.Therapeutic advances in endocrinology and metabolism · 2026Review
- Can Model-Informed Precision Dosing of Beta-Lactams in Critical Care Improve Clinical Outcomes?Chemotherapy · 2026Review
- Whole Body Physiologically Based Pharmacokinetic Model to Explain A Patient With Drug-Drug Interaction Between Voriconazole and Flucloxacillin.European journal of drug metabolism and pharmacokinetics · 2024Article
- Influence of ultrafiltration conditions on the measurement of unbound drug concentrations: flucloxacillin as an example.The Journal of antimicrobial chemotherapy · 2024Article
- In silico evaluation of a beta-lactam dosing guideline among adults with serious infections.Pharmacotherapy · 2023Article
- Hypoalbuminemia and Pharmacokinetics: When the Misunderstanding of a Fundamental Concept Leads to Repeated Errors over Decades.Antibiotics (Basel, Switzerland) · 2023Review
- Target attainment and population pharmacokinetics of flucloxacillin in critically ill patients: a multicenter study.Critical care (London, England) · 2023Observational
- Variability of Isavuconazole Trough Concentrations during Longitudinal Therapeutic Drug Monitoring.Journal of clinical medicine · 2022Article
- Optimal dosing of cefotaxime and desacetylcefotaxime for critically ill paediatric patients. Can we use microsampling?The Journal of antimicrobial chemotherapy · 2022Article
- Population Pharmacokinetics of Temocillin Administered by Continuous Infusion in Patients with Septic Shock Associated with Intra-Abdominal Infection and Ascitic Fluid Effusion.Antibiotics (Basel, Switzerland) · 2022Article
- High unbound flucloxacillin fraction in critically ill patients.The Journal of antimicrobial chemotherapy · 2021Observational
- Probability of pharmacological target attainment with flucloxacillin in Staphylococcus aureus bloodstream infection: a prospective cohort study of unbound plasma and individual MICs.The Journal of antimicrobial chemotherapy · 2021Article
- Pharmacokinetic/Pharmacodynamic Target Attainment Based on Measured versus Predicted Unbound Ceftriaxone Concentrations in Critically Ill Patients with Pneumonia: An Observational Cohort Study.Antibiotics (Basel, Switzerland) · 2021Article
- Hypoalbuminemia as Surrogate and Culprit of Infections.International journal of molecular sciences · 2021Review
- Could simulation methods solve the curse of sparse data within clinical studies of antibiotic resistance?JAC-antimicrobial resistance · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInitial appropriate anti-infective therapy is associated with improved outcomes in patients with severe infections. In critically ill patients, altered pharmacokinetic (PK) behaviour is common and known to influence the achievement of PK/pharmacodynamic targets.
objectivesTo describe population PK and optimized dosing regimens for flucloxacillin in critically ill patients.
methodsFirst, we developed a population PK model, estimated between-patient variability (BPV) and identified covariates that could explain BPV through non-linear mixed-effects analysis, using total and unbound concentrations obtained from 35 adult critically ill patients treated with intermittent flucloxacillin. Second, we validated the model using external datasets from two different countries. Finally, frequently prescribed dosing regimens were evaluated using Monte Carlo simulations.
resultsA two-compartment model with non-linear protein binding was developed and validated. BPV of the maximum binding capacity decreased from 42.2% to 30.4% and BPV of unbound clearance decreased from 88.1% to 71.6% upon inclusion of serum albumin concentrations and estimated glomerular filtration rate (eGFR; by CKD-EPI equation), respectively. PTA (target of 100%fT>MIC) was 91% for patients with eGFR of 33 mL/min and 1 g q6h, 87% for patients with eGFR of 96 mL/min and 2 g q4h and 71% for patients with eGFR of 153 mL/min and 2 g q4h.
conclusionsFor patients with high creatinine clearance who are infected with moderately susceptible pathogens, therapeutic drug monitoring is advised since there is a risk of underexposure to flucloxacillin. Due to the non-linear protein binding of flucloxacillin and the high prevalence of hypoalbuminaemia in critically ill patients, dose adjustments should be based on unbound concentrations.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.