Trial reportIntensive care medicine2022
Model-informed precision dosing of beta-lactam antibiotics and ciprofloxacin in critically ill patients: a multicentre randomised clinical trial.
Trial report in Intensive care medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses 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.
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
68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- [S3 guideline on renal replacement therapy in intensive care medicine : Evidence-based implementation of renal replacement therapy in critically ill patients].Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2025Guideline
- Pooled it
- A prospective feasibility study evaluating the implementation of model-informed precision dosing in critically ill children.Frontiers in pharmacology · 2026Trial
- Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis.Intensive care medicine · 2024Trial
- Plasma protein binding of ceftriaxone in critically ill patients: can we predict unbound fractions?The Journal of antimicrobial chemotherapy · 2023Trial
- From early recognition to precision medicine: advances in the diagnosis and management of adult sepsis and septic shock-a narrative review.Infection · 2026Review
- Implementing a Model-Informed Precision Dosing Service for Cefepime in a Quaternary Children's Hospital: A First-Year Experience.Therapeutic drug monitoring · 2026Article
- Therapeutic drug monitoring of high-dosage intravenous flucloxacillin and mortality in patients with Staphylococcus aureus bacteremia: a retrospective cohort study using inverse probability weighting.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Rising Carbapenem MICs and Clinical Dose Optimization: Bridging Resistance Surveillance and Pharmacokinetic/Pharmacodynamic Strategies.Antibiotics (Basel, Switzerland) · 2026Review
- Pyridoxic Acid as a Novel Endogenous Biomarker for OAT-Mediated Clearance of Meropenem: A Population Pharmacokinetic Modeling and PK/PD-Response Analysis in Patients with Sepsis.Pharmaceutics · 2026Article
- From Intelligent Operating Room to Smart ICU: Digital Continuity, AI-Supported Decision-Making and CRRT as a Model of Pharmacokinetic Personalization in Critical Care.Healthcare (Basel, Switzerland) · 2026Review
- Model-informed vancomycin precision dosing by population pharmacokinetics combined with machine learning algorithms.British journal of clinical pharmacology · 2026Article
- A Retrospective Cohort Study to Optimize Piperacillin/Tazobactam Dosing in Routine Intensive-Care Patients via a Newly Designed Clinical Pharmacy Service Including TDM- and Algorithm-Based Recommendations.Pharmacy (Basel, Switzerland) · 2026Article
- Article
- Dose as a fundamental organizing principle in physiology: Implications for mechanism, disease, and precision medicine.Journal of precision medicine (Amsterdam, Netherlands) · 2026Article
- Bayesian Dosing Simulator (BDS): A Pharmacokinetic Modeling Tool for Optimized Antibiotic Therapy.Pharmacotherapy · 2026Article
- Uncertainty undermines the validity of antimicrobial pharmacodynamics.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Encephalopathy in mechanically ventilated adult patients in the intensive care unit: the role of β-Lactam overdosing.Scientific reports · 2026Article
- β-Lactam dosing in critically ill children: predictors for target non-attainment.The Journal of antimicrobial chemotherapy · 2026Observational
- Newer antibiotics for drug-resistant Gram-negative infections in immunocompromised hosts: from pivotal trials to high-risk practice.Frontiers in cellular and infection microbiology · 2026Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
Abstract
purposeIndividualising drug dosing using model-informed precision dosing (MIPD) of beta-lactam antibiotics and ciprofloxacin has been proposed as an alternative to standard dosing to optimise antibiotic efficacy in critically ill patients. However, randomised clinical trials (RCT) on clinical outcomes have been lacking.
methodsThis multicentre RCT, including patients admitted to the intensive care unit (ICU) who were treated with antibiotics, was conducted in eight hospitals in the Netherlands. Patients were randomised to MIPD with dose and interval adjustments based on monitoring serum drug levels (therapeutic drug monitoring) combined with pharmacometric modelling of beta-lactam antibiotics and ciprofloxacin. The primary outcome was ICU length of stay (LOS). Secondary outcomes were ICU mortality, hospital mortality, 28-day mortality, 6-month mortality, delta sequential organ failure assessment (SOFA) score, adverse events and target attainment.
resultsIn total, 388 (MIPD n = 189; standard dosing n = 199) patients were analysed (median age 64 [IQR 55-71]). We found no significant differences in ICU LOS between MIPD compared to standard dosing (10 MIPD vs 8 standard dosing; IRR = 1.16; 95% CI 0.96-1.41; p = 0.13). There was no significant difference in target attainment before intervention at day 1 (T1) (55.6% MIPD vs 60.9% standard dosing; p = 0.24) or at day 3 (T3) (59.5% vs 60.4%; p = 0.84). There were no significant differences in other secondary outcomes.
conclusionsWe could not show a beneficial effect of MIPD of beta-lactam antibiotics and ciprofloxacin on ICU LOS in critically ill patients. Our data highlight the need to identify other approaches to dose optimisation.
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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.