Preventing Postoperative Staphylococcus aureus Infections The Search Continues Preventing Postoperative S aureus Infections

Malani PN. — Wed, 03 Apr 2013 00:00:00 GMT

Among carefully selected patients, cardiac surgery can enhance both quality and duration of life. Today, procedures such as coronary artery bypass graft surgery (CABG) and valve replacement/repair are commonplace, with more than 400 000 median sternotomies for these and other procedures performed annually in the United States. Despite the potential benefits, infectious complications remain a significant source of postoperative morbidity, with Staphylococcus aureus infections topping the list; in the setting of a new valve or endograft, such infections are associated with case-fatality rates of nearly 50%. For patients who develop serious staphylococcal infections after cardiac surgery, any operative benefit can be negated by a complex and lengthy postoperative treatment course involving additional procedures (debridement, flap closure) and extended therapy with parenteral antimicrobials. Given the enormous adverse consequences of infectious complications on surgical outcomes, prevention efforts grounded in the best evidence remain essential.

Effect of an Investigational Vaccine for Preventing Staphylococcus aureus Infections After Cardiothoracic Surgery A Randomized Trial Preventing Poststernotomy S aureus Infections

Fowler VG, Allen KB, Moreira ED, et al. — Wed, 03 Apr 2013 00:00:00 GMT

Importance

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.

Design, Setting, and Participants

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.

Intervention

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).

Main Outcome Measures

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 and Relevance

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.

Trial Registration

clinicaltrials.gov Identifier: NCT00518687

JAMA: Surgical Infections Topic Collection

Preventing Postoperative Staphylococcus aureus Infections The Search Continues Preventing Postoperative S aureus Infections

Effect of an Investigational Vaccine for Preventing Staphylococcus aureus Infections After Cardiothoracic Surgery A Randomized Trial Preventing Poststernotomy S aureus Infections