Trial reportThe Journal of antimicrobial chemotherapy2023
Plasma protein binding of ceftriaxone in critically ill patients: can we predict unbound fractions?
Trial report in The Journal of antimicrobial chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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.
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
6 citing papers in PubMed, 8 citations in OpenAlex.
- Structure-Activity Relationship Studies for 1,3,4-Thiadiazole-Based Bacterial Carbonic Anhydrase Inhibitors withJournal of medicinal chemistry · 2026Article
- β-Lactam dosing in critically ill children: predictors for target non-attainment.The Journal of antimicrobial chemotherapy · 2026Observational
- Review
- Leveraging Clinical Data to Enhance the Performance Evaluation of Ceftriaxone Population Pharmacokinetic Models in Children.Clinical pharmacokinetics · 2025Article
- Glutamine potentiates cefoperazone-sulbactam activity againstFrontiers in microbiology · 2025Article
- Clinical Experience with Off-Label Intrathecal Administration of Selected Antibiotics in Adults: An Overview with Pharmacometric Considerations.Antibiotics (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStandard antibiotic dosing is not suitable for critically ill patients, due to altered pharmacokinetics (PK) in these patients. Knowledge of protein binding is important for optimizing antibiotic exposure because only the unbound fraction is pharmacologically active. If unbound fractions can be predicted, minimal sampling techniques and less costly methods can be routinely used.
methodsData from the DOLPHIN trial, a prospective randomized clinical trial that included critically ill patients, were used. Total and unbound ceftriaxone concentrations were determined using a validated UPLC-MS/MS method. A non-linear saturable binding model was made using 75% of the trough concentrations and validated on the remaining data. Our model and previously published models were tested for their performance for subtherapeutic (<1 mg/L) and high (>10 mg/L) unbound concentrations.
resultsIn total, 113 patients were sampled [Acute Physiology And Chronic Health Evaluation version 4 (APACHE IV) score 71 (IQR 55-87), albumin 28 g/L (IQR 24-32)]. This resulted in 439 samples (trough = 224, peak = 215). Unbound fractions were significantly different between samples taken at trough and peak times [10.9% (IQR 7.9-16.4) versus 19.7% (IQR 12.9-26.6), P < 0.0001], which was not explained by concentration differences. Our model and most literature models showed good sensitivity and low specificity to determine high and subtherapeutic ceftriaxone trough concentrations using only the total ceftriaxone and albumin concentrations.
conclusionsCeftriaxone protein binding is not concentration related in critically ill patients. Existing models show good ability to predict high concentrations, but low specificity in predicting subtherapeutic concentrations.
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