title: Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial.
abstract: OBJECTIVE
  Infections due to Staphylococcus aureus are serious complications of cardiothoracic surgery. A novel vaccine candidate (V710) containing the highly conserved S. aureus iron surface determinant B is immunogenic and generally well tolerated in volunteers.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of preoperative vaccination in preventing serious postoperative S. aureus infection in patients undergoing cardiothoracic surgery.
  
  
  METHODS
  Double-blind, randomized, event-driven trial conducted between December 2007 and August 2011 among 8031 patients aged 18 years or older who were scheduled for full median sternotomy within 14 to 60 days of vaccination at 165 sites in 26 countries.
  
  
  METHODS
  Participants were randomly assigned to receive a single 0.5-mL intramuscular injection of either V710 vaccine, 60 μg (n = 4015), or placebo (n = 4016).
  
  
  METHODS
  The primary efficacy end point was prevention of S. aureus bacteremia and/or deep sternal wound infection (including mediastinitis) through postoperative day 90. Secondary end points included all S. aureus surgical site and invasive infections through postoperative day 90. Three interim analyses with futility assessments were planned.
  
  
  RESULTS
  The independent data monitoring committee recommended termination of the study after the second interim analysis because of safety concerns and low efficacy. At the end of the study, the V710 vaccine was not significantly more efficacious than placebo in preventing either the primary end points (22/3528 V710 vaccine recipients [2.6 per 100 person-years] vs 27/3517 placebo recipients [3.2 per 100 person-years]; relative risk, 0.81; 95% CI, 0.44-1.48; P = .58) or secondary end points despite eliciting robust antibody responses. Compared with placebo, the V710 vaccine was associated with more adverse experiences during the first 14 days after vaccination (1219/3958 vaccine recipients [30.8%; 95% CI, 29.4%-32.3%] and 866/3967 placebo recipients [21.8%; 95% CI, 20.6%-23.1%], including 797 [20.1%; 95% CI, 18.9%-21.4%] and 378 [9.5%; 95% CI, 8.6%-10.5%] with injection site reactions and 66 [1.7%; 95% CI, 1.3%-2.1%] and 51 [1.3%; 95% CI, 1.0%-1.7%] with serious adverse events, respectively) and a significantly higher rate of multiorgan failure during the entire study (31 vs 17 events; 0.9 [95% CI, 0.6-1.2] vs 0.5 [95% CI, 0.3-0.8] events per 100 person-years; P = .04). Although the overall incidence of vaccine-related serious adverse events (1 in each group) and the all-cause mortality rate (201/3958 vs 177/3967; 5.7 [95% CI, 4.9-6.5] vs 5.0 [95% CI, 4.3-5.7] deaths per 100 person-years; P = .20) were not statistically different between groups, the mortality rate in patients with staphylococcal infections was significantly higher among V710 vaccine than placebo recipients (15/73 vs 4/96; 23.0 [95% CI, 12.9-37.9] vs 4.2 [95% CI, 1.2-10.8] per 100 person-years; difference, 18.8 [95% CI, 8.0-34.1] per 100 person-years).
  
  
  CONCLUSIONS
  Among patients undergoing cardiothoracic surgery with median sternotomy, the use of a vaccine against S. aureus compared with placebo did not reduce the rate of serious postoperative S. aureus infections and was associated with increased mortality among patients who developed S. aureus infections. These findings do not support the use of the V710 vaccine for patients undergoing surgical interventions.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00518687.
authors.affiliation: Duke University Medical Center, Hanes Bldg, Room 153, Trent Drive, PO Box 102359, Durham, NC 27710, USA. fowle003@mc.duke.edu
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
authors.forename: Keith B
authors.initials: KB
authors.lastname: Allen
authors.forename: Edson D
authors.initials: ED
authors.lastname: Moreira
authors.forename: Moustafa
authors.initials: M
authors.lastname: Moustafa
authors.forename: Frank
authors.initials: F
authors.lastname: Isgro
authors.forename: Helen W
authors.initials: HW
authors.lastname: Boucher
authors.forename: G Ralph
authors.initials: GR
authors.lastname: Corey
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Carmeli
authors.forename: Robert
authors.initials: R
authors.lastname: Betts
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Hartzel
authors.forename: Ivan S F
authors.initials: IS
authors.lastname: Chan
authors.forename: Tessie B
authors.initials: TB
authors.lastname: McNeely
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kartsonis
authors.forename: Dalya
authors.initials: D
authors.lastname: Guris
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Onorato
authors.forename: Steven S
authors.initials: SS
authors.lastname: Smugar
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.forename: Ajoke
authors.initials: A
authors.lastname: Sobanjo-ter Meulen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000401:mortality / Q000517:prevention & control*; D013504:Cardiovascular Surgical Procedures; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D013203:Staphylococcal Infections / Q000401:mortality / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects*; D013211:Staphylococcus aureus; D056346:Sternotomy / Q000009:adverse effects*; D013530:Surgical Wound Infection / Q000517:prevention & control*; D019616:Thoracic Surgical Procedures / Q000009:adverse effects; D014611:Vaccination; D055815:Young Adult
chemical_list: D013209:Staphylococcal Vaccines; C579630:V710 vaccine