What Is the Best Vancomycin Therapeutic Drug Monitoring Parameter to Assess Efficacy? A Critical Review of Experimental Data and Assessment of the Need for Individual Patient Minimum Inhibitory Concentration Value
Bibliographic record
Abstract
Therapeutic drug monitoring is recommended for the use of vancomycin, but a recent widely publicized US medical society consensus statement has changed the suggested optimal method(s) of dose adjustment. Specifically, 24 h area under the curve (AUC24)-based monitoring is has been recommended for vancomycin in preference to monitoring of trough concentrations. One reason cited for this change is the claim that AUC24 is a superior correlate to efficacy than trough (Cmin). Evidence from a number of retrospective analyses have been critically reviewed and determined to have weaknesses. This narrative review focuses on the experimental studies performed in vivo in animal models of infection and in vitro to determine the extent to which these data may provide a compelling distinction between pharmacokinetic/pharmacodynamics (PKPD) parameters that may translate to clinical use in therapeutic drug monitoring. Animal in vivo studies have been presented at conferences, but no original peer reviewed studies could be found that compare various PKPD parameters. These conference proceeding findings were supportive but unconvincing, even though they were favorably presented subsequently in review articles and clinical practice guidelines. In vitro data are somewhat conflicting, but the range of concentrations may play a role in the discrepancies found. It has been suggested that MIC may be assumed to have a value of 1 mg/L; however, it can be demonstrated that this assumption may lead to considerable discrepancy from results with an actual MIC value. The AUC24 parameter has been weighed against the percentage of time above the MIC (%T > MIC) as a comparative PKPD parameter, yet this may be an inappropriate comparison for vancomycin since all clinically useful dosing provides 100% T > MIC. Regardless, there is a distinction between clinical TDM parameters and PKPD parameters, so, in practice, the change to AUC24:MIC based on animal experiments and in vitro evidence for vancomycin may be premature.
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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 | 0.000 |
| 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 | 0.001 | 0.001 |
| 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".