Trial reportAntimicrobial agents and chemotherapy2007
Population pharmacokinetics at two dose levels and pharmacodynamic profiling of flucloxacillin.
Trial report in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses 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
31 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Optimization of the treatment with beta-lactam antibiotics in critically ill patients-guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique-SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et Réanimation-SFAR).Critical care (London, England) · 2019Guideline
- Interethnic differences in pharmacokinetics of antibacterials.Clinical pharmacokinetics · 2015Pooled it
- A Population Pharmacokinetic Analysis of Continuous Infusion of Cloxacillin duringAntimicrobial agents and chemotherapy · 2020Trial
- Competitive inhibition of renal tubular secretion of gemifloxacin by probenecid.Antimicrobial agents and chemotherapy · 2009Trial
- Synergistic activity of fosfomycin and flucloxacillin against methicillin-susceptible and methicillin-resistant Staphylococcus aureus: in vitro and in vivo assessment.Medical microbiology and immunology · 2025Article
- Article
- Predicting Volume of Distribution in Neonates: Performance of Physiologically Based Pharmacokinetic Modelling.Pharmaceutics · 2023Article
- Identification of flucloxacillin-modified hepatocellular proteins: implications in flucloxacillin-induced liver injury.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Developmental Pharmacokinetics of Antibiotics Used in Neonatal ICU: Focus on Preterm Infants.Biomedicines · 2023Review
- Pharmacodynamics of Flucloxacillin in a Neutropenic Murine Thigh Infection Model: A Piece of the Puzzle towards Evidence-Based Dosing.Antibiotics (Basel, Switzerland) · 2022Article
- 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
- Flucloxacillin bone and soft tissue concentrations assessed by microdialysis in pigs after intravenous and oral administration.Bone & joint research · 2021Article
- Optimization of flucloxacillin dosing regimens in critically ill patients using population pharmacokinetic modelling of total and unbound concentrations.The Journal of antimicrobial chemotherapy · 2020Article
- Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro.Antibiotics (Basel, Switzerland) · 2020Article
- Calculated initial parenteral treatment of bacterial infections: Pharmacokinetics and pharmacodynamics.GMS infectious diseases · 2020Article
- Meropenem-Tobramycin Combination Regimens Combat Carbapenem-Resistant Pseudomonas aeruginosa in the Hollow-Fiber Infection Model Simulating Augmented Renal Clearance in Critically Ill Patients.Antimicrobial agents and chemotherapy · 2019Article
- Evaluation of Tobramycin and Ciprofloxacin as a Synergistic Combination Against HypermutablePharmaceutics · 2019Article
- Characterization of kinetics of human cytochrome P450s involved in bioactivation of flucloxacillin: inhibition of CYP3A-catalysed hydroxylation by sulfaphenazole.British journal of pharmacology · 2019Article
- Meropenem Combined with Ciprofloxacin Combats Hypermutable Pseudomonas aeruginosa from Respiratory Infections of Cystic Fibrosis Patients.Antimicrobial agents and chemotherapy · 2018Article
- Polymyxin B in Combination with Enrofloxacin Exerts Synergistic Killing against Extensively Drug-Resistant Pseudomonas aeruginosa.Antimicrobial agents and chemotherapy · 2018Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Flucloxacillin is often used for the treatment of serious infections due to sensitive staphylococci. The pharmacokinetic (PK)-pharmacodynamic (PD) breakpoint of flucloxacillin has not been determined by the use of population PK. Targets based on the duration of non-protein-bound concentrations above the MIC (fT(>MIC)) best correlate with clinical cure rates for beta-lactams. We compared the breakpoints for flucloxacillin between several dosage regimens. In a randomized, two-way crossover study, 10 healthy volunteers received 500 mg and 1,000 mg flucloxacillin as 5-min intravenous infusions. Drug concentrations were determined by high-pressure liquid chromatography. We used the programs WinNonlin for noncompartmental analysis and statistics and NONMEM for population PK and Monte Carlo simulation. We compared the probability of target attainment (PTA) for intermittent- and continuous-dosage regimens based on the targets of fT(>MIC)s of > or =50% and > or =30% of the dosing interval. The clearance and the volume of distribution were very similar after the administration of 500 mg and 1,000 mg flucloxacillin. We estimated renal and nonrenal clearances of 5.37 liters/h (coefficient of variation, 19%) and 2.73 liters/h (33%). For near maximal killing (target, fT(>MIC) of > or =50%) flucloxacillin showed a robust (> or =90%) PTA up to MICs of 0.75 to 1 mg/liter (PTA of 86% at 1 mg/liter) for a continuous or a prolonged infusion of 6 g/day. Short-term infusions of 6 g/day had a lower breakpoint of 0.25 to 0.375 mg/liter. The flucloxacillin PK was linear for doses of 500 mg and 1,000 mg. Prolonged and continuous infusion at a 66% lower daily dose achieved the same PK-PD breakpoints as short-term infusions. Prolonged infusion and continuous infusion are appealing options for the treatment of serious infections caused by sensitive staphylococci.
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