The Staph Vaccine: Stay Nosy

Lynda Szczech, MD, MSCE


June 05, 2013

In This Article

Vaccines for S aureus in ESRD Patients: Background

The Studies

Moustafa M, Aronoff GR, Chandran C, et al. Phase IIa study of the immunogenicity and safety of the novel Staphylococcus aureus vaccine V710 in adults with end-stage renal disease receiving hemodialysis. Clin Vaccine Immunol. 2012;19:1509-1616. Accessed May 14, 2013.

Fowler VG, Allen KB, Moreira ED, et al. Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA. 2013;309:1368-1378


People with end-stage renal disease (ESRD) experience a 20.6% mortality in the first year after starting dialysis.[1] The risk for mortality related to infection is highest in this period and continues to remain a significant threat after that first year.

Patients with ESRD are hospitalized 1.8 times per year on average. Whereas the all-cause hospitalization rate for patients undergoing dialysis has fallen by approximately 3% over the last decade, this small decline actually represents a balance between decreasing rates of hospitalization for vascular access (declining by 49.7%) and increasing rates of hospitalizations for infections (rising by 43.1%).[1] This risk is present not only when the infection occurs but also after surviving an infection: Approximately 40% of patients will be either rehospitalized or will die within the following 30 days.

Staphylococcus aureus accounts for approximately 80% of the organisms isolated from catheter-related infections among patients with ESRD.[2] Because S aureus organisms are encapsulated, they are less easily phagocytosed by leukocytes. In addition to minimizing catheter use and maximizing catheter hygiene, an additional strategy to lessen the frequency of S aureus infection and the morbidity and mortality associated with it includes vaccination against the organism. Given the benefit of other vaccinations against widely prevalent bacterial infections, such as Streptococcus pneumoniae, arguably this strategy could significantly affect disease burden in patients receiving dialysis.

In 2002, we had a glimpse of that potential. A phase 3 trial of a vaccine against the type 5 and 8 polysaccharides conjugated to recombinant Pseudomonas exotoxin A (StaphVAX™) was performed in 1804 patients receiving hemodialysis.[3] These antigens were chosen for the vaccine because they comprise the bulk of the isolates seen in human S aureus infections.

Patients with vascular access using either an arteriovenous (AV) graft or fistula were randomly assigned to receive a single injection of vaccine or placebo and followed for the occurrence of S aureus bacteremia. The primary hypothesis that the vaccine would protect against infection during weeks 3-54, unfortunately, was not supported by the data. During this period, the vaccine was 36% effective in reducing S aureus infections; however, this was not statistically significant (95% confidence interval [CI], -24% to 57%; P = .23).

Additional exploratory analyses were performed to glean information that would inform future research. During weeks 3-40, the vaccine reduced the incidence of bacteremia by 57% (95% CI, 10%-81%; P = .02). Similar to the decline in efficacy seen after week 40, antibody levels to the type 5 and 8 capsular polysaccharides rose before week 26 but subsequently declined at week 54.

Furthermore, post hoc subgroup analyses suggested that patients with nasal carriage of Staphylococcus may have benefited to a greater extent from the vaccine than those without nasal carriage. Compared with placebo, rates of infection in the vaccinated group with nasal carriage were reduced from 7.8% to 4.9% in patients with AV grafts and from 7.5% to 0% in patients with AV fistulae. No differences were observed in the risk for infection between the placebo and vaccinated groups among those without nasal carriage.

A larger, phase 3 trial of 3600 patients was subsequently performed to test the efficacy of the vaccine from weeks 3 to 34.[4] This second trial, however, failed to reflect the same positive results, and little additional information as to why has been made subsequently available. With little hope that StaphVAX would now be developed for the ESRD population, creating other vaccines to provide protection for this population became important.


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