title: Systematic review and network meta-analysis of tedizolid for the treatment of acute bacterial skin and skin structure infections caused by MRSA.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: York Health Economics Consortium, Enterprise House, Innovation Way, University of York, Heslington, York, YO10 5NQ, UK. Rachael.mccool@york.ac.uk.
authors.forename: Rachael
authors.initials: R
authors.lastname: McCool
authors.affiliation: Aberdeen Royal Infirmary, Foresterhill Road, Aberdeen, AB25 2ZN, UK.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Gould
authors.affiliation: York Health Economics Consortium, Enterprise House, Innovation Way, University of York, Heslington, York, YO10 5NQ, UK.
authors.forename: Jacqui
authors.initials: J
authors.lastname: Eales
authors.affiliation: Quantics, 28 Drumsheugh Gardens, Edinburgh, EH3 7RN, UK.
authors.forename: Teresa
authors.initials: T
authors.lastname: Barata
authors.affiliation: York Health Economics Consortium, Enterprise House, Innovation Way, University of York, Heslington, York, YO10 5NQ, UK.
authors.forename: Mick
authors.initials: M
authors.lastname: Arber
authors.affiliation: Quantics, 28 Drumsheugh Gardens, Edinburgh, EH3 7RN, UK.
authors.forename: Kelly
authors.initials: K
authors.lastname: Fleetwood
authors.affiliation: York Health Economics Consortium, Enterprise House, Innovation Way, University of York, Heslington, York, YO10 5NQ, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Glanville
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Kauf
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001499:Bayes Theorem; D002511:Cephalosporins / Q000627:therapeutic use; D017576:Daptomycin / Q000627:therapeutic use; D006801:Humans; D000069349:Linezolid / Q000627:therapeutic use; D055624:Methicillin-Resistant Staphylococcus aureus / Q000472:pathogenicity*; D010755:Organophosphates / Q000627:therapeutic use; D010080:Oxazoles / Q000627:therapeutic use; D023303:Oxazolidinones / Q000627:therapeutic use*; D017192:Skin Diseases, Bacterial / Q000188:drug therapy*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013777:Tetrazoles / Q000627:therapeutic use*; D014640:Vancomycin / Q000627:therapeutic use; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D017576:Daptomycin; D000069349:Linezolid; D010755:Organophosphates; D010080:Oxazoles; D023303:Oxazolidinones; D013777:Tetrazoles; D014640:Vancomycin; D000097583:Ceftaroline; C546016:tedizolid; C515040:tedizolid phosphate
keywords: Acute bacterial skin and skin structure infections; Antibacterial; Complicated skin and skin structure infections; Methicillin-resistant Staphylococcus aureus; Network meta-analysis; Systematic review