The Activity of Tedizolid Against Gram-Positive Pathogens Isolated From Patients in USA Medical Centers: 2014 Surveillance
Bibliographic record
Abstract
Background. Tedizolid (TZD) is approved for treatment of acute bacterial skin and skin structure infections in the United States of America (USA), European Union (EU), and Canada. The in vitro activity of TZD was tested against Gram-positive pathogens isolated collected from USA medical centers in 2014. Methods. In 2014, 5999 Gram-positive, non-duplicate, non-consecutive, single patient clinical isolates were collected from 29 medical centers across all nine USA census regions. Isolates were tested for antibacterial susceptibility (S) as per CLSI guidelines. MIC values for TZD and linezolid (LZD) were read both at (1) the first well where trailing begins (80% read; TZD80 and LZD80) as per CLSI M07-A10 and (2) at endpoint (100% growth inhibition; TZD100 and LZD100). USA-FDA, CLSI, and EUCAST breakpoints were used to determine %S. Results. A total of 3441 S. aureus strains were evaluated; 100% of strains were S to TZD. The MIC50/90 values for TZD80 (MIC50/90, 0.12/0.12 µg/mL) were one dilution lower than TZD100 (0.25/0.25 µg/mL) and four-fold lower than for LZD (LZD80, MIC50/90, 1/1 µg/mL; LZD100, MIC50/90, 1/2 µg/mL). Against 344 coagulase-negative staphylococci, TDZ80/100 (MIC50/90, 0.06-0.12/0.12-0.25 µg/mL) was four- to eight-fold more potent than LZD80/100 (MIC50/90, 0.5-1/0.5-1 µg/mL). TZD was active (80/100 MIC90, 0.25/0.5 µg/mL) against 524 Enterococcus spp. and 100.0% of 343 E. faecium isolates were S by USA-FDA breakpoint of ≤0.5 µg/mL (using TZD100). Against 563 β-hemolytic streptococci, 100.0% of isolate were S to LZD100 (MIC50/90, 1/1 µg/mL) and TZD100 (MIC50/90, 0.12/0.25 µg/mL). Against 260 viridans group streptococci, 100.0% of isolate were S to LZD100 (MIC50/90, 0.5/1 µg/mL) and TZD100 was two- to four-fold more potent (MIC50/90, 0.12/0.25 µg/mL).TZD100 was also very active (MIC50/90, 0.25/0.25 µg/mL) against 867 pneumococcal isolates. Conclusion. TZD demonstrated higher in vitro activity (two- to four-fold) than LZD when tested against Gram-positive pathogens isolated from patients in USA medical centers during 2014. MIC distributions and MIC50/90 values for TZD and LZD read without regard for pinpoint trailing colonies were one dilution lower than those read at 100% inhibition. Disclosures. D. J. Farrell, Merck & Co. Inc: Research Contractor, Research support; R. K. Flamm, Merck & Co. Inc: Research Contractor, Research support; R. E. Mendes, Merck & Co. Inc: Research Contractor, Research support; R. N. Jones, Merck & Co. Inc: Research Contractor, Research support.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.001 | 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".