Pharmacokinetics and Pharmacodynamics of Oral Cephalexin in Children With Osteoarticular Infections
Bibliographic record
Abstract
BACKGROUND: Osteoarticular infections lead to significant morbidity in children. Cephalexin has in vitro activity against methicillin-susceptible Staphylococcus aureus, a predominant pathogen in osteoarticular infection. However, cephalexin pharmacokinetics (PK) and pharmacodynamics (PD) are poorly described in children. This study described cephalexin PK in children treated for osteoarticular infection and assessed the proportion of children achieving surrogate PK/PD target for efficacy in methicillin-susceptible S. aureus infection. METHODS: Children with osteoarticular infection, 1 to 18 years of age, were eligible for this study if they were receiving oral cephalexin per standard of care. PK plasma samples were collected at specified times after multiple doses. PK parameters were estimated using noncompartmental analysis. PK/PD target for efficacy was calculated using the child's PK parameters, minimum inhibitory concentration (MIC) of the isolate when available and previously described MIC of 2 and 4 mg/L. RESULTS: Twelve children were enrolled and PK profiles were obtained from 11 of them. Median age was 7 years, and median cephalexin dose was 40 mg/kg/dose every 8 hours. Median apparent oral clearance, apparent oral volume of distribution and elimination half-life (T1/2) were 0.29 L/h/kg, 0.44 L/kg and 1.1 h, respectively. Time above MIC (T>MIC) was greater than 40% of the dosing interval in 100%, 90% and 80% of the children when MICs were 0.25, 2 and 4 mg/L, respectively. CONCLUSIONS: Oral cephalexin achieved optimal plasma exposure and was well tolerated in children with osteoarticular infection. Correlation between osteoarticular infection clinical outcome and PK/PD parameters needs further evaluation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".