Pharmacokinetics and safety of fosfomycin and flomoxef administered as part of neonatal sepsis treatment (NeoSep1 Part 1)
Bibliographic record
Abstract
Neonatal doses for the off-patent antibiotics fosfomycin and flomoxef, which offer coverage against many extended-spectrum beta-lactamase (ESBL)-producing organisms, are based on limited data. We performed a pharmacokinetic (PK) and safety study of fosfomycin and flomoxef to confirm proposed neonatal dosing before further investigation in a trial (NeoSep1, ISRCTN48721236). Neonates with suspected sepsis, weighing more than 1,000 g, were sequentially enrolled into three antibiotic treatment cohorts: fosfomycin and amikacin (Cohort 1), flomoxef and amikacin (Cohort 2), and flomoxef and fosfomycin (Cohort 3), and followed for 28 days. Plasma samples were taken for PK assessment, with population PK modeling and simulations performed. Sixty-two neonates (48/62 [77%] preterm; 48/62 [77%] ≤7 days postnatal age [PNA]) received at least one dose of study antibiotics. Fosfomycin and flomoxef plasma concentrations were best described by a two-compartment and a one-compartment model, respectively, with postmenstrual age and PNA significantly influencing clearance. The probability of target attainment for fosfomycin was 100% for minimum inhibitory concentrations (MICs) of up to 8 mg/L, and for flomoxef, it was 100% for MICs of up to 0.5 mg/L. Adverse events (AEs) were common in this critically ill cohort. Thirteen (21%) neonates developed 19 trial antibiotic-related AEs (17 with grade ≤2, and 2 of grade 3), none of which required modification or discontinuation of allocated treatment. Seven neonates (11.6%) died. In this predominately preterm population, fosfomycin and flomoxef were safe, with drug exposures similar to published studies supporting the proposed doses for the larger, randomized NeoSep1 trial.This study is registered with ISRCTN48721236.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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".