Systematic review and network meta-analysis of tedizolid for the treatment of acute bacterial skin and skin structure infections caused by MRSA
Bibliographic record
Abstract
BACKGROUND: Tedizolid, the active moiety of tedizolid phosphate, is approved in the United States, the European Union, Canada and a number of other countries for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This network meta-analysis (NMA) evaluates the comparative effectiveness of tedizolid and other antibacterials indicated for the treatment of ABSSSI caused by MRSA. METHODS: Systematic review of 10 databases was undertaken to inform an NMA to estimate the relative effectiveness of tedizolid and established monotherapy comparators (ceftaroline, daptomycin, linezolid, teicoplanin, tigecycline, vancomycin) for treating MRSA-associated ABSSSI. Randomized controlled trials enrolling adults with ABSSSI or complicated skin and skin structure infections caused by suspected/documented MRSA were eligible for inclusion. Networks were developed based on similarity of study design, patient characteristics, outcome measures and available data. Outcomes of interest included clinical response at end of therapy (EOT), post-therapy evaluation (PTE) or test-of-cure assessment and treatment discontinuations resulting from adverse events (AEs). Bayesian NMA was conducted for each outcome using fixed-effects and random effects models. RESULTS: Literature searches identified 3,618 records; 15 trials met the inclusion criteria and were considered suitable for NMA comparison. In fixed-effects models, tedizolid had higher odds of clinical response at EOT (odds ratio [OR], 1.7; credible interval, 1.0, 3.0) and PTE than vancomycin (OR, 1.6; credible interval, 1.1, 2.5). No differences in odds of clinical response at EOT or PTE were observed between tedizolid and other comparators. There was no evidence of a difference among treatments for discontinuation due to AEs. Results from random effects and fixed-effects models were generally consistent. CONCLUSIONS: Tedizolid was superior to vancomycin for clinical response at EOT and PTE. There was no evidence of a difference between tedizolid and other comparators and no evidence of a difference between tedizolid and all comparators when evaluating discontinuation due to AEs. These findings suggest that tedizolid provides an alternative option for the management of serious skin infections caused by suspected or documented MRSA. This study is subject to the limitations inherent in all NMAs, and the results should be interpreted accordingly.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.010 | 0.004 |
| 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".