title: Systematic Review and Meta-Analysis To Estimate Antibacterial Treatment Effect in Acute Bacterial Skin and Skin Structure Infection.
abstract: A systematic literature review and meta-analysis were conducted to estimate the antibacterial treatment effect for linezolid and ceftaroline to inform on the design of acute bacterial skin and skin structure infection (ABSSSI) noninferiority trials. The primary endpoints included an early clinical treatment response (ECTR) defined as cessation of lesion spread at 48 to 72 h postrandomization and the test-of-cure (TOC) response defined as total resolution of the infection at 7 to 14 days posttreatment. The systematic review identified no placebo-controlled trials in ABSSSI, 4 placebo-controlled trials in uncomplicated skin and soft tissue infection as a proxy for placebo in ABSSSI, 12 linezolid trials in ABSSSI, 3 ceftaroline trials in ABSSSI, and 2 trials for nonantibacterial treatment. The ECTR rates at 48 to 72 h and corresponding 95% confidence intervals (CI) were 78.7% (95% CI, 61.1 to 96.3%) for linezolid, 74.0% (95% CI, 69.7 to 78.3%) for ceftaroline, and 59.0% (95% CI, 52.8 to 65.3%) for nonantibacterial treatment. The early clinical treatment effect could not be estimated, given no available placebo or proxy for placebo data for this endpoint. Clinical, methodological, and statistical heterogeneity influenced the selection of trials for the meta-analysis of the TOC treatment effect estimation. The pooled estimates of the TOC treatment response were 31.0% (95% CI, 6.2 to 55.9%) for the proxy for placebo, 88.1% (95% CI, 81.0 to 95.1%) for linezolid, and 86.1% (95% CI, 83.7 to 88.6%) for ceftaroline. The TOC clinical treatment effect estimation was 25.1% for linezolid and 27.8% for ceftaroline. The antibacterial treatment effect estimation at TOC will inform on the design and analysis of future noninferiority ABSSSI clinical trials.
authors.affiliation: University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Jordan E
authors.initials: JE
authors.lastname: Cates
authors.affiliation: GlaxoSmithKline (GSK), Research Triangle Park, North Carolina, USA fanny.s.mitrani-gold@gsk.com.
authors.forename: Fanny S
authors.identifier: http://orcid.org/0000-0001-8829-7088
authors.initials: FS
authors.lastname: Mitrani-Gold
authors.affiliation: GSK, Collegeville, Pennsylvania, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: GSK, Collegeville, Pennsylvania, USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Mundy
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use; D006801:Humans; D000069349:Linezolid / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012867:Skin / Q000382:microbiology*; D017192:Skin Diseases, Bacterial / Q000188:drug therapy*; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000069349:Linezolid; D000097583:Ceftaroline