Interference of Oritavancin on Coagulation Tests as Assessed In Vitro and in a Phase 1 Study of Normal Healthy Volunteers
Bibliographic record
Abstract
Background. Oritavancin (ORI) is a lipoglycopeptide (LG) antibiotic approved as a single-dose treatment of adults with acute bacterial skin and skin structure infections caused by gram-positive pathogens. As some LG and lipopeptide (LP) antibiotics are known to interfere with phospholipid (PL)-dependent coagulation tests (CT), we assessed the effects of ORI on common CT and determined the time-to-resolution (TtR) of test interference. Methods. For testing of clinical samples, plasma was obtained from normal healthy volunteers (NHV; n= 20) at defined time intervals following a 3h infusion of a single 1200 mg dose of ORI in a Phase 1 study. For in vitro testing, ORI was spiked into human plasma over a concentration range of 2 to 47 µg/ml. PL-dependent CT included prothrombin time (PT), activated partial thromboplastin time (APTT), Dilute Russell Viper Venom Test (DRVVT), activated clotting time (ACT), silica clot time (SCT) and activated ain C Resistance (APCR). PL-independent CT included chromogenic anti-factor Xa (anti-FXa), thrombin time (TT) and an assay to diagnose heparin-induced thrombocytopenia (anti-heparin-PF4). The TtR of each test interference was the interval from the start of the ORI infusion to the time the result returned to the normal reference range. Results. Transient prolongation of PT, APTT, DRVVT, ACT and SCT occurred in plasma samples obtained from NHVs in the phase 1 study (table). Using ORI-spiked human plasma in vitro, prolongation of coagulation in the affected tests occurred in a concentration-dependent manner. ORI did not interfere with assays for APCR, anti-FXa, TT, or anti-heparin-PF4. Conclusion. Although ORI has no effect of the coagulation system, it can cause artificial elevations in some laboratory CT. Because of its single-dose regimen, the transient interference of ORI on these CT does not require further consideration beyond the specified TtR of test interference in contrast to some LG and LP antibiotics that require daily administration. Disclosures. A. Belley, The Medicines Company: Employee, Salary R. Robson, The Medicines Company: Investigator, Research support J. Francis, The Medicines Company: Consultant, Consulting fee D. Adcock, The Medicines Company: Research Contractor, Research support S. Tiefenbacher, The Medicines Company: Research Contractor, Research support C. M. Rubino, The Medicines Company: Research Contractor, Research support G. Moeck, The Medicines Company: Employee, Salary D. Sylvester, The Medicines Company: Employee, Salary M. Dudley, The Medicines Company: Employee, Salary J. Loutit, The Medicines Company: Employee, Salary
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".