A prospective cohort feasibility study of real-time beta-lactam antimicrobial therapeutic drug monitoring in critically ill patients with lower respiratory infection: The TDM-TIME study
Bibliographic record
Abstract
Background: Critically ill patients with lower respiratory tract infections often fail to achieve therapeutic beta-lactam antibiotic concentrations, despite standard dosing. Therapeutic drug monitoring (TDM) may improve attaining drug exposure, but delayed turnaround times limit its clinical impact. The objective of this study was to evaluate the feasibility of delivering real-time beta-lactam TDM results within two dosing intervals. Methods: We conducted a single-centre prospective cohort feasibility study in two ICUs in Manchester, UK. Critically ill adult patients receiving piperacillin/tazobactam or meropenem for suspected or confirmed lower respiratory infection were enrolled. Blood samples were collected for analysis and drug quantification, with the primary outcome being the proportion of TDM results returned within two dosing intervals. Secondary outcomes included detailed time-to-result, clinical and microbiological outcomes. TDM results were not released to clinical teams. Results: We recruited 30 participants, of whom 20 (67%) had TDM results available within two dosing intervals. The median time from blood sampling to TDM result was 10.9 h, with a median time from antimicrobial initiation to result of 25.4 h. At 28 days, 70% of participants were alive, with a median (IQR) ICU and hospital length of stay of 7 (5-25) and 17 (10-27) days, respectively. Resistant pathogen strains were isolated in 4/21 (19%) participants. Discussion: Recruitment of critically ill participants into a time-sensitive trial of TDM is feasible. Timely feedback of beta-lactam TDM results to clinicians is achievable, however, barriers to streamlined around-the-clock implementation remain. Future clinical trials of beta-lactam TDM should factor turnaround times into study design. Registration: NCT05971979.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".