ArticleEuropean journal of drug metabolism and pharmacokinetics2026
Defining Safe and Effective Cefazolin Dosing Regimens for MSSA Infections in the CNS: Leveraging Sparse Real-World Data and PBPK Modeling.
Article in European journal of drug metabolism and pharmacokinetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveInfections in the central nervous system (CNS) are serious and carry a significant risk of morbidity and mortality. Though commonly used as prophylaxis for neurosurgical interventions, cefazolin as a treatment for CNS infections due to methicillin-susceptible Staphylococcus aureus (MSSA) has been debated owing to the perceived inability to achieve adequate concentrations at the site of infection. The objective of the current study was to evaluate the dose-exposure-response relationship of cefazolin in the CNS.
methodsTo leverage sparse data of cefazolin in the cerebrospinal fluid (CSF) and derive an understanding of the dose-exposure-response profile in the CNS, a physiologically-based pharmacokinetic (PBPK) model was created in PK-Sim. Simulations were performed using standard cefazolin dosing of 2000 mg every 8 h and alternative regimens to maximize the probability of target attainment (PTA). The pharmacodynamic target used was 100% fT > MIC (100% of free drug concentrations above the minimum inhibitory concentration). Furthermore, a neurotoxicity threshold of ≥ 300 mg/L and ≥ 30 mg/L for trough concentrations was set as the safety indicator in plasma and CSF, respectively.
resultsThe cefazolin CSF-PBPK model was successfully validated such that predicted CSF:plasma ratios were within a 1.5-fold error compared with the observed values. In addition, the median predicted CSF:epidemiological cut-off (ECOFF) concentration ratio was 2.52, compared with an observed value of 2.8. In silico simulations demonstrate that intermittent doses of 2000 mg every 6 h or a continuous infusion of 8-10 g/day may be required to ensure 90% PTA for MSSA to a MIC ≤ 2 mg/L. Predicted plasma and CSF concentrations were well below concentrations associated with neurotoxicity.
conclusionsThis study is the first to use sparse observed CNS data to develop a mechanistic model to describe the pharmacokinetics of cefazolin in the CSF. This work supports existing research on the viability of cefazolin as a therapeutic alternative for CNS infections attributed to MSSA and can be used for future clinical trial planning.
Indexed as
Identifiers
41642564What 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.