Complicated skin and skin-structure infections and catheter-related bloodstream infections: noninferiority of linezolid in a phase 3 study.
BACKGROUND
Catheter-related bloodstream infection (CRBSI) causes substantial morbidity and mortality, but few randomized, controlled studies have been conducted to guide therapeutic interventions.


METHODS
To determine whether linezolid would be noninferior to vancomycin in patients with CRBSI, we conducted an open-label, multicenter, comparative study. Patients with suspected CRBSI were randomized to receive linezolid or vancomycin (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 patients with suspected CRBSI; patients 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 linezolid recipients, 89.6% [146 for 163 patients]; for the control group, 89.9% [134 of 149]; 95% CI, -7.1 to 6.4) and CRBSI (for linezolid 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 linezolid recipients (28 of 269 patients) and 10.1% for control subjects (26 of 257) in the modified intent-to-treat population (i.e., all patients with gram-positive baseline culture) through test of cure, and they were 21.5% for linezolid recipients (78 of 363) and 16.0% for the control group (58 of 363; 95% CI, -0.2 to 11.2) for all treated patients through poststudy treatment day 84.


CONCLUSIONS
Linezolid demonstrated microbiologic success rates noninferior to those for vancomycin in patients with cSSSIs and CRBSIs caused by gram-positive organisms. Patients with catheter-related infections must be carefully investigated for the heterogeneous underlying causes of high morbidity and mortality, particularly for infections with gram-negative organisms.
Wilcox
Mark H
MH
Department of Microbiology, Leeds General Infirmary and University of Leeds Teaching Hospitals, Leeds, England.
Tack
Kenneth J
KJ
Bouza
Emilio
E
Herr
Daniel L
DL
Ruf
Bernhard R
BR
Ijzerman
M Marian
MM
Croos-Dabrera
Rodney V
RV
Kunkel
Mark J
MJ
Knirsch
Charles
C
D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality; D055499:Catheter-Related Infections / Q000188:drug therapy* / Q000401:mortality; D003428:Cross Infection / Q000188:drug therapy / Q000401:mortality; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000401:mortality; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000401:mortality; D014640:Vancomycin / Q000009:adverse effects / Q000627:therapeutic use
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid