ArticleAntibiotics (Basel, Switzerland)2021
Pharmacokinetic/Pharmacodynamic Target Attainment Based on Measured versus Predicted Unbound Ceftriaxone Concentrations in Critically Ill Patients with Pneumonia: An Observational Cohort Study.
Article in Antibiotics (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review.Frontiers in pharmacology · 2022Pooled it
- Pharmacokinetics of Subcutaneous and Intravenous Ceftriaxone in an Older Population: The PhASAge Study.Open forum infectious diseases · 2025Trial
- Plasma protein binding of ceftriaxone in critically ill patients: can we predict unbound fractions?The Journal of antimicrobial chemotherapy · 2023Trial
- Unraveling Ceftriaxone Dosing: Free Drug Prediction, Threshold Optimization, and Model Validation.The AAPS journal · 2025Article
- Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review.Antibiotics (Basel, Switzerland) · 2024Review
- Predicting Beta-Lactam Target Non-Attainment in ICU Patients at Treatment Initiation: Development and External Validation of Three Novel (Machine Learning) Models.Antibiotics (Basel, Switzerland) · 2023Article
- Hypoalbuminemia and Pharmacokinetics: When the Misunderstanding of a Fundamental Concept Leads to Repeated Errors over Decades.Antibiotics (Basel, Switzerland) · 2023Review
- Aerosol Inhalation Delivery of Ceftriaxone in Mice: Generation Procedure, Pharmacokinetics, and Therapeutic Outcome.Antibiotics (Basel, Switzerland) · 2022Article
- Retrospective Comparison of the Effectiveness and Safety of Ceftriaxone 1 g Twice Daily versus 2 g Once Daily for Treatment of Aspiration Pneumonia.Antibiotics (Basel, Switzerland) · 2022Article
- Biomarkers Predicting Tissue Pharmacokinetics of Antimicrobials in Sepsis: A Review.Clinical pharmacokinetics · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The impact of ceftriaxone pharmacokinetic alterations on protein binding and PK/PD target attainment still remains unclear. We evaluated pharmacokinetic/pharmacodynamic (PK/PD) target attainment of unbound ceftriaxone in critically ill patients with severe community-acquired pneumonia (CAP). Besides, we evaluated the accuracy of predicted vs. measured unbound ceftriaxone concentrations, and its impact on PK/PD target attainment. A prospective observational cohort study was carried out in adult patients admitted to the intensive care unit with severe CAP. Ceftriaxone 2 g q24h intermittent infusion was administered to all patients. Successful PK/PD target attainment was defined as unbound trough concentrations above 1 or 4 mg/L throughout the whole dosing interval. Acceptable overall PK/PD target attainment was defined as successful target attainment in ≥90% of all dosing intervals. Measured unbound ceftriaxone concentrations (CEFu) were compared to unbound concentrations predicted from various protein binding models. Thirty-one patients were included. The 1 mg/L and 4 mg/L targets were reached in 26/32 (81%) and 15/32 (47%) trough samples, respectively. Increased renal function was associated with the failure to attain both PK/PD targets. Unbound ceftriaxone concentrations predicted by the protein binding model developed in the present study showed acceptable bias and precision and had no major impact on PK/PD target attainment. We showed suboptimal (i.e., <90%) unbound ceftriaxone PK/PD target attainment when using a standard 2 g q24h dosing regimen in critically ill patients with severe CAP. Renal function was the major driver for the failure to attain the predefined targets, in accordance with results found in general and septic ICU patients. Interestingly, CEFu was reliably predicted from CEFt without major impact on clinical decisions regarding PK/PD target attainment. This suggests that, when carefully selecting a protein binding model, CEFu does not need to be measured. As a result, the turn-around time and cost for ceftriaxone quantification can be substantially reduced.
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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.