Complicated skin and skin-structure infections and catheter-related bloodstream infections: noninferiority of XXXX in a phase 3 study.

@entity1 @entity1212 @entity2176 @entity281 @entity5136
BACKGROUND: Catheter-related @entity281 (CRBSI) causes substantial morbidity and mortality, but few randomized, controlled studies have been conducted to guide therapeutic interventions. METHODS: To determine whether @entity5136 would be noninferior to @entity2176 in @entity1 with CRBSI, we conducted an open-label, multicenter, comparative study. @entity1 with suspected CRBSI were randomized to receive @entity5136 or @entity2176 (control group). The primary end point was microbiologic outcome at test of cure 1-2 weeks after treatment, as assessed by step-down procedure. The first analysis population was complicated skin and skin structure infection (cSSSI) in @entity1 with suspected CRBSI; @entity1 with CRBSI were analyzed if noninferiority criteria (lower bound of the 95% confidence interval [CI] not outside -15%) were met. RESULTS: Noninferiority criteria were met for cSSSI (microbiologic success rate for @entity5136 recipients, 89.6% [146 for 163 @entity1 ]; for the control group, 89.9% [134 of 149]; 95% CI, -7.1 to 6.4) and CRBSI (for @entity5136 recipients, 86.3% [82 of 95]; for the control group, 90.5% [67 of 74]; 95% CI, -13.8 to 5.4). The frequency and severity of adverse events were similar between groups. Mortality rates were 10.4% for @entity5136 recipients (28 of 269 @entity1 ) and 10.1% for control subjects (26 of 257) in the modified intent-to-treat population (i.e., all @entity1 with gram-positive baseline culture) through test of cure, and they were 21.5% for @entity5136 recipients (78 of 363) and 16.0% for the control group (58 of 363; 95% CI, -0.2 to 11.2) for all treated @entity1 through poststudy treatment day 84. CONCLUSIONS: @entity5136 demonstrated microbiologic success rates noninferior to those for @entity2176 in @entity1 with cSSSIs and CRBSIs caused by gram-positive organisms. @entity1 with @entity1212 must be carefully investigated for the heterogeneous underlying causes of high morbidity and mortality, particularly for infections with gram-negative organisms.
