Efficacy of a 4-Antigen <i>Staphylococcus aureus</i> Vaccine in Spinal Surgery: The <i>STaphylococcus aureus</i> suRgical Inpatient Vaccine Efficacy (STRIVE) Randomized Clinical Trial
Hamid Hassanzadeh, James Baber, Elizabeth Begier, David C. Noriega, Hiroaki Konishi, Yoshiyuki Yato, Michael Y. Wang, Jean Charles Le Huec, Vikas V. Patel, Péter Varga, Ulf Liljenqvist, John Conly, Charu Sabharwal, Iona Munjal, David Cooper, David Radley, Anna Jaques, Michael A. Patton, William C. Gruber, Kathrin U. Jansen, Annaliesa S. Anderson, Alejandra Gurtman, for the STaphylococcus aureus suRgical Inpatient Vaccine Efficacy Investigator Team, Jonathan M. Zenilman, Robert A. Salata, William Schaffner, William C. Blackwelder, David Leaper
Abstract
BACKGROUND: Staphylococcus aureus is a global pathogen that is frequently responsible for healthcare-associated infections, including surgical site infections (SSIs). Current infection prevention and control approaches may be limited, with S. aureus antibiotic resistance remaining problematic. Thus, a vaccine to prevent or reduce S. aureus infection is critically needed. We evaluated the efficacy and safety of an investigational 4-antigen S. aureus vaccine (SA4Ag) in adults undergoing elective open posterior spinal fusion procedures with multilevel instrumentation. METHODS: In this multicenter, site-level, randomized, double-blind trial, patients aged 18-85 years received a single dose of SA4Ag or placebo 10-60 days before surgery. SA4Ag efficacy in preventing postoperative S. aureus bloodstream infection and/or deep incisional or organ/space SSIs was the primary end point. Safety evaluations included local reactions, systemic events, and adverse events (AEs). Immunogenicity and colonization were assessed. RESULTS: Study enrollment was halted when a prespecified interim efficacy analysis met predefined futility criteria. SA4Ag showed no efficacy (0.0%) in preventing postoperative S. aureus infection (14 cases in each group through postoperative day 90), despite inducing robust functional immune responses to each antigen compared with placebo. Colonization rates across groups were similar through postoperative day 180. Local reactions and systemic events were mostly mild or moderate in severity, with AEs reported at similar frequencies across groups. CONCLUSIONS: In patients undergoing elective spinal fusion surgical procedures, SA4Ag was safe and well tolerated but, despite eliciting substantial antibody responses that blocked key S. aureus virulence mechanisms, was not efficacious in preventing S. aureus infection. Clinical Trials Registration. NCT02388165.