ArticleAntibiotics (Basel, Switzerland)2022
Pharmacodynamics of Flucloxacillin in a Neutropenic Murine Thigh Infection Model: A Piece of the Puzzle towards Evidence-Based Dosing.
Article in Antibiotics (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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.
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
2 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.
- Systematic review of antimicrobial pharmacokinetic/pharmacodynamic indices in murine thigh and hollow fibre dose fractionation studies analysed with a standard method.The Journal of antimicrobial chemotherapy · 2026Pooled it
- Staphylococcus aureus vertebral osteomyelitis: a single-centre retrospective cohort study with focus on oral flucloxacillin follow-up.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For decades, flucloxacillin has been used to treat methicillin-susceptible Staphylococcus aureus (MSSA). Little is still known about its pharmacodynamics (PD). The present study aimed to determine the pharmacokinetic (PK)/PD index and the PD-index value minimally required for efficacy. MICs of 305 MSSA isolates were measured to determine the wild-type distribution. The PD of 8 S. aureus, 1 S. pyogenes, and 1 S. agalactiae isolates were evaluated in a neutropenic murine thigh infection model. Two S. aureus isolates were used in a dose-fractionation study and a dose−response analysis was performed additionally in the in vivo model. Data were analyzed with a population PK and sigmoid maximum effect model. The end of the wild-type distribution was 1 mg/L. The percentage of time the unbound concentration was above MIC (%fT > MIC) was best correlated with efficacy. For S. aureus, median %fT > 0.25 × MIC required for 1-log reduction was 15%. The value for S. pyogenes was 10%fT > MIC and for S. agalactiae 22%fT > 0.25xMIC for a 1-log reduction. The effect of flucloxacillin reached a 2-log reduction of S. aureus at 20%fT > 0.25xMIC and also for S. pyogenes and S. agalactiae, a reduction was reached. These data may serve to optimize dosing regimens currently used in humans.
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Registered trials
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