Preventing Staphylococcal Bacteremia: Beginning of a New Era?
May 15, 2002 4 minutes read
Abstract & Commentary
Synopsis: In this pilot study of a novel vaccine, the incidence of Staphylococcus aureus bacteremia was reduced by 57% in a group of hemodialysis patients.
Source: Shinefield H, et al. N Engl J Med. 2002;346:491-496.
Staphylococcus aureus ranks among the most frequent causes of skin and soft tissue infection, surgical and other traumatic wound infection, osteomyelitis and septic arthritis, infective endocarditis, and hospital-acquired bacteremia. With the emergence of methicillin resistance in 40-50% of S aureus strains throughout the world, this microorganism has become a major therapeutic challenge. Because infection control methods have had only limited success, other effective preventive strategies—such as immunization—would be welcome.
In this study, Shinefield and colleagues tested a candidate vaccine in hemodialysis patients in a randomized trial. The vaccine, composed of 2 S aureus capsular polysaccharides (types 5 and 8) bound to a nontoxic protein, a recombinant variant of Pseudomonas aeruginosa exotoxin A, was administered to almost 900 patients, and a placebo was given to a comparable group of similar size. Enrolled patients were 18 years of age or older, had received hemodialysis treatment for at least 8 weeks, and had a Karnofsky score of at least 50. All were free of infection for at least 2 weeks before entry into the study. Demographic and clinical characteristics were similar; mean age was 58 years. Nasal carriage of S aureus was documented in 22% of subjects. Mild-to-moderate local reactions, malaise, and myalgia were experienced by nearly 40%, 25%, and 28%, respectively, of vaccine recipients. Other side effects such as headache, vomiting, and fever occurred with equal frequency in the 2 groups of subjects.
The occurrence of S aureus bacteremia was reduced by more than half—57% to be exact—during weeks 3 to 40 following vaccine administration, while fatality rates in the 2 study groups were similar. There was no demonstrable reduction in bacteremia rates in the period from 40-54 weeks after vaccination. Type 5 and type 8 isolates accounted for 33% and 46%, respectively, of S aureus blood culture strains from vaccine recipients. The 2 types constituted 27% and 54% of staphylococcal blood culture isolates, respectively, in placebo recipients, but these differences were not statistically significant.
Shinefield et al estimated the level of protective antibody to be 80 µg/mL at 40 weeks after vaccination, a concentration achieved by 75-80% of vaccine recipients. Geometric mean levels of antibody declined to less than 80 µg/mL 1 year after vaccine administration.
Shinefield et al hypothesize that antibody levels may have declined partly as a result of hemodialysis, and suggest that booster doses of vaccine should be investigated as a means to provide more long-lasting protection. They also opine that, because hemodialysis patients generally respond to vaccines less robustly than do non-dialysis patients (without end-stage renal disease), the vaccine may have greater efficacy in other high-risk patient groups.
Comment by Jerry D. Smilack, MD, FACP
S aureus infections have been responsible for untold numbers of deaths and morbidity of cosmic proportions over the span of history. With the availability of penicillin in the early 1940s came the hope that a long era of human suffering might draw to a close, but such was not the case. Staphylococci quickly became resistant to penicillin and, subsequently, to methicillin and its congeners. The specter of resistance to vancomycin looms ominously as we look ahead to the 21st century, and preventing staphylococcal infections is becoming a high priority. Efforts to develop vaccines effective against S aureus have moved with fits and starts. Vaccine development has languished over the years, largely due to a sense of complacency about the ability of antibiotics to eradicate infection. Now that interest in developing a vaccine has resurfaced, several investigators have reported products that elicit protective antistaphylococcal antibody.1-3 In this article from the Kaiser Permanente Vaccine Study Center in Oakland, Calif, we see the first glimmer of hope that an effective vaccine may be on the horizon.
Bacterial capsular polysaccharides inhibit polymorphonuclear cell opsonophagocytosis. Antibody to the polysaccharide blocks this inhibition and thereby promotes host defenses. Because staphylococcal polysaccharide itself is a weak immunogen, it must be linked to an adjuvant, in this case a bacterial exoprotein (a nontoxic variant of exotoxin A produced by P aeruginosa). The vaccine reported in this trial was comprised of capsular polysaccharides from 2 S aureus types that result in nearly 85% of all clinical infections. Shinefield et al administered the vaccine to hemodialysis patients, a group at considerably increased risk of serious staphylococcal infections, including bacteremia. They found that staphylococcal bacteremia occurred less than half as often in subjects who received vaccine compared with placebo recipients. Protection was demonstrated to last as long as 40 weeks. Shinefield et al did not state whether nonbacteremic staphylococcal infection rates were altered in vaccine recipients.
This study represents a major advance in the effort to combat staphylococcal disease. More research is needed to determine whether longer lasting protection can be achieved with booster doses in the hemodialysis population, and whether greater protective effect can be afforded other high-risk patient groups, such as diabetics, patients with HIV infection, and illicit drug users.
Dr. Smilack,, Infectious Disease Consultant, Mayo Clinic Scottsdale, Scottsdale, AZ, is Associate Editor of Infectious Disease Alert.
References
1. McKenney D, et al. Science. 1999;284:1523-1527.
2. Flock JI. Mol Med Today. 1999;5:532-537.
3. Mamo W. Microbiol Immunol. 2000;44:381-384.
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