OAKLAND, CALIF—Each year, 3% to 4% of patients with end-stage renal disease (ESRD) who are undergoing hemodialysis contract bacteremia caused by Staphylococcus aureus, which may result in severe complications or death. Further, increasing prevalence of drug-resistant S aureus strains makes treatment more difficult. In a recent phase III study, a new conjugate vaccine conferred partial immunity and protection against S aureus bacteremia in ESRD hemodialysis patients for up to 40 weeks.[1]

“This is the first human trial of a conjugate staphylococcal vaccine to look for efficacy,” said Henry Shinefield, MD, codirector of the Kaiser Permanente Vaccine Study Center in Oakland, California, and first author of the study. With this vaccine, he noted, “we reduced staph infections by 57% among ESRD patients on hemodialysis.”.

S aureus bacteremia is a serious problem in ESRD hemodialysis patients, who are immunocompromised, Dr. Shinefield told PULMONARY REVIEWS. It frequently causes severe complications and death in this population. Thus, a strategy that prevents S aureus bacteremia from developing could improve outcomes in these patients, as well as in other at-risk groups.

HOW THE VACCINE WORKS

Immune responses stimulated with staphylococcal capsular polysaccharides alone are weak, Dr. Shinefield explained. To compensate for this, he said, the new vaccine “combines a recombinant Pseudomonas exotoxin A with capsular polysaccharides from S aureus type 5 and type 8 strains and produces high serum levels of anti-capsular antibodies. The vaccine protects against S aureus type 5 and type 8, which account for 85% of clinical isolates of S aureus.”

In a double-blind trial, Dr. Shinefield and colleagues randomized 1,804 ESRD patients at 73 hemodialysis centers to receive an intramuscular injection with either vaccine or saline. Serum samples were taken before inoculation, and six, 26, 54, and 67 weeks after vaccination. Patients were instructed to record reactions to the vaccine in the first week following the injections. They were also monitored for the development of bacteremia for at least 54 weeks after vaccination.

Compared with the 910 controls, the 893 vaccine recipients showed a significantly higher incidence of local reactions, myalgia, and malaise. However, Dr. Shinefield pointed out, “These symptoms were self-limiting and resolved within a few days.”

Although ESRD hemodialysis patients are known to be an immunocompromised population, the vaccine stimulated a satisfactory immune response in almost 90% of recipients: “High anti-staphylococcal– antibody serum levels were produced,” Dr. Shinefield noted. At week 6, mean levels of antibodies to type 5 and type 8 capsular polysaccharides were 230 and 206 µg/mL, respectively, in vaccinated patients, versus 5.6 and 8.6 µg/mL, respectively, in controls. In 80% of the vaccinated patients, anti–type-5 antibody levels reached 80 µg/mL, estimated as the minimum concentration needed to provide protection against S aureus; anti–type-8 antibodies attained this level in 75%. After 40 weeks, levels in the vaccinated group declined.

VACCINE CONFERS PARTIAN IMMUNITY

Incidence of S aureus bacteremia was reduced by 57% in vaccine recipients between weeks 3 and 40 after inoculation; 11 cases occurred in the vaccine recipients, compared with 26 in the placebo cohort. After 40 weeks, however, bacteremia incidence among vaccinated patients paralleled declines in antibody levels.

Typing of the S aureus bacteremia cases in the vaccinated group identified 33% as type 5, 46% as type 8, and 21% as type 336 (which bears a recently identified polysaccharide not included in the vaccine). Proportions in the placebo group were similar.

Other researchers have reported that combining albuterol with nebulized lidocaine may also help prevent this initial bronchoconstriction.[2] The effects of the two drugs may be additive, suggesting benefits with combined therapy, said Dr. Hunt.

VACCINE MAY GUARD OTHERS

“Since the vaccine’s efficacy was 57% in these immunocompromised individuals, I’d expect protection to be at least as great or greater in those who are not immunocompromised,” Dr. Shinefield remarked. Consequently, immunoprophylaxis might yield even more benefit for other groups than for ESRD patients on dialysis.

S aureus causes a variety of potentially deadly infections, including metastatic abscesses, septic arthritis, endocarditis, osteomyelitis, and wound infections. Thus, Dr. Shinefield envisions a number of populations as candidate vaccine recipients. “It might be beneficial for use in individuals undergoing surgical procedures if given two to three weeks preoperatively,” he suggested. The vaccine could also be used in nursing home residents or other patients chronically at risk for S aureus infection.

“If further [testing] shows a booster response to a second immunization, a repeat inoculation might extend the period of protection for groups at chronic risk,” Dr. Shinefield speculated. “Future vaccines might also incorporate the polysaccharide from strain 336, the type responsible for approximately one fifth of the S aureus infections encountered in our study.”

—Mimi Zucker, PhD

References
Shinefield H, Black S, Fattom A, et al. Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis. N Engl J Med. 2002;346:491-496.

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