Prevention of nosocomial Staphylococcus aureus infections after rapid detection and eradication of S. aureus carriage in patients at risk; a randomized placebo controlled multi-centre trial

Staphylococcus aureus is a frequent cause of nosocomial infections, including bacteremia and wound infections. Approximately twenty-five percent of all nosocomial infections are caused by S. aureus, affecting both surgical and non-surgical patients, and leading to increased hospital stay, antibiotic use, costs, and mortality. Nasal carriers of S. aureus have an increased risk of developing these infections. Recent data show that eighty percent of nosocomial bacteremic S. aureus strains are endogenous and similar to the strain from the nose of S. aureus carriers. Since 20-55% of patients admitted to the hospital is a carrier of this pathogen, a substantial number of these nosocomial infections may be prevented by eliminating S. aureus from the nose. Intranasal application of mupirocin for five days successfully eradicates S. aureus from the nose and leads to a reduction of S. aureus hand carriage. Mupirocin prophylaxis has been proven effective in preventing nosocomial S. aureus infections in randomized placebo controlled trials among dialysis and surgical patients, and patients with recurrent skin infections. Earlier, our research group studied the efficacy of mupirocin in a randomized placebo controlled study in a non-surgical patient population of S. aureus carriers. Patients were either assigned to a short course of mupirocin or placebo after a nasal culture grew S. aureus. No differences were observed in the rates of nosocomial S. aureus infections, in-hospital mortality, or in duration of hospitalization, between the mupirocin and the placebo group. There were several explanations for this lack in efficacy: (1) mupirocin prophylaxis was started after nasal cultures grew S. aureus, which caused a significant delay in eradication. S. aureus infections can occur during or before the prophylaxis treatment. Therefore, it is essential to determine carriage status and start prophylaxis soon after admission, (2) our previous study was not targeted on risk groups for S. aureus disease. Since a general population was studied, the incidence of nosocomial S. aureus infections was very low (2.8%), and the statistical power to detect significant differences was insufficient. Furthermore, many patients were already discharged within 4-5 days and therefore had a minimal risk for S. aureus infection, (3) mupirocin treatment was not repeated for patients with prolonged hospital stay, to prevent recolonization. Patients with prolonged hospital stay contributed considerably to the number of episodes of S. aureus disease. To prevent recolonization the intervention, like mupirocin, should be repeated. (4) sole mupirocin treatment is not sufficient for eradication of S. aureus. Patients may recolonize from extra-nasal sites, which can be prevented with skin disinfection. Chlorhexidine, a disinfectant soap, has a proven efficacy in significantly reducing S. aureus from the skin. We want to perform a new clinical randomized placebo-controlled multi-center trial in which we take these points into account. We screen patients admitted to departments were there is an increased risk for S. aureus disease (nephrology, surgery, oncology, gastro-enterology, intensive care) for nasal S. aureus carriage with fast molecular techniques on the day of admission. Screen-positive patients, with an expected hospital stay of at least 4 days, are randomised to mupirocin nasal ointment and skin disinfection or placebo nasal ointment and placebo skin disinfection within 24 hours after admission. The treatment is repeated after two weeks in patients still admitted. Primary endpoint is: nosocomial S. aureus infection, defined according to standard criteria (CDC). Secundary endpoints are: mortality due to all causes and due to S. aureus infections, duration of hospital stay, and time from admission to infection. We performed an analysis based on our previous study results, in which we excluded patients who had nosocomial S. aureus before the end of their prophylaxis treatment. This showed that 50% of nosocomial bacteremia (the most serious infection) may be prevented by mupirocin treatment alone, which would be cost-effective. Therefore, we expect that by targeting on a high risk patient population, by repeating the treatment, by intensifying the treatment with skin disinfection, by starting treatment on the day of admission, we can reduce nosocomial S. aureus infection by at least 50%. The proposed intervention has as a goal to reduce nosocomial S. aureus infection and is simple, easy to implement, innovative, has few side-effects, and focusses on prevention of a frequently occurring, serious nosocomial infection.