ArticleThe Journal of antimicrobial chemotherapy2021
Probability of pharmacological target attainment with flucloxacillin in Staphylococcus aureus bloodstream infection: a prospective cohort study of unbound plasma and individual MICs.
Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Therapeutic drug monitoring and the role of pharmacokinetics/pharmacodynamics in optimizing beta-lactam antibiotic dosing for deep-seated infections: a systematic review.The Journal of antimicrobial chemotherapy · 2026Pooled it
- 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
- A review of the randomized clinical trial results from the Staphylococcus aureus network adaptive platform (SNAP) meticillin-susceptible (MSSA) and penicillin-susceptible (PSSA) domains and CloCeBa.The Journal of antimicrobial chemotherapy · 2026Review
- The challenge of antimicrobial resistance (AMR): current status and future prospects.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Target Attainment and Population Pharmacokinetics of Cefazolin in Patients with InvasiveAntibiotics (Basel, Switzerland) · 2024Article
- Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review.Antibiotics (Basel, Switzerland) · 2024Review
- Exploring the Impact of Model-Informed Precision Dosing on Procalcitonin Concentrations in Critically Ill Patients: A Secondary Analysis of the DOLPHIN Trial.Pharmaceutics · 2024Article
- Clinical Characteristics and Predictors of Mortality of Patients with Post-Neurosurgical Meningitis-A 900-Cases Cohort Study.Infection and drug resistance · 2024Article
- Meropenem PK/PD Variability and Renal Function: "We Go Together".Pharmaceutics · 2023Article
- Beta-Lactam Dose Optimisation in the Intensive Care Unit: Targets, Therapeutic Drug Monitoring and Toxicity.Antibiotics (Basel, Switzerland) · 2023Review
- Early Target Attainment With Continuous Infusion Meropenem and Piperacillin/Tazobactam and Utilization of Therapeutic Drug Monitoring in Critically Ill Patients: A Retrospective Cohort Study From 2017 to 2020.Open forum infectious diseases · 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
- Pharmacodynamics of Flucloxacillin in a Neutropenic Murine Thigh Infection Model: A Piece of the Puzzle towards Evidence-Based Dosing.Antibiotics (Basel, Switzerland) · 2022Article
- High unbound flucloxacillin fraction in critically ill patients.The Journal of antimicrobial chemotherapy · 2021Observational
- Limitations of Antibiotic MIC-Based PK-PD Metrics: Looking Back to Move Forward.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesMSSA bloodstream infections (BSIs) are associated with considerable mortality. Data regarding therapeutic drug monitoring (TDM) and pharmacological target attainment of the β-lactam flucloxacillin are scarce. PATIENTS AND
methodsWe determined the achievement of pharmacokinetic/pharmacodynamic targets and its association with clinical outcome and potential toxicity in a prospective cohort of 50 patients with MSSA-BSI. Strain-specific MICs and unbound plasma flucloxacillin concentrations (at five different timepoints) were determined by broth microdilution and HPLC-MS, respectively.
resultsIn our study population, 48% were critically ill and the 30 day mortality rate was 16%. The median flucloxacillin MIC was 0.125 mg/L. The median unbound trough concentration was 1.7 (IQR 0.4-9.3), 1.9 (IQR 0.4-6.2) and 1.0 (IQR 0.6-3.4) mg/L on study day 1, 3 and 7, respectively. Optimal (100% fT>MIC) and maximum (100% fT>4×MIC) target attainment was achieved in 45 (90%) and 34 (68%) patients, respectively, throughout the study period. Conversely, when using the EUCAST epidemiological cut-off value instead of strain-specific MICs, target attainment was achieved in only 13 (26%) patients. The mean unbound flucloxacillin trough concentration per patient was associated with neurotoxicity (OR 1.12 per 1 mg/L increase, P = 0.02) and significantly higher in deceased patients (median 14.8 versus 1.7 mg/L, P = 0.01).
conclusionsFlucloxacillin pharmacological target attainment in MSSA-BSI patients is frequently achieved when unbound flucloxacillin concentrations and strain-specific MICs are considered. However, currently recommended dosing regimens may expose patients to excessive flucloxacillin concentrations, potentially resulting in drug-related organ damage.
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