Does Eradication of Staphylococci from the Nose Reduce Nosocomial Infection in Nonsurgical Patients?

Abstract & Commentary

Synopsis: Mupirocin application to the nose of hospitalized Staphylococcus aureus carriers did not decrease the incidence of nosocomial S aureus infection, but it did delay its appearance.

Source: Wertheim HFL, et al. Mupirocin prophylaxis against nosocomial Staphylococcus aureus infections in nonsurgical patients. Ann Intern Med. 2004;140:419-425.

This study is an attempt to determine whether eradication of Staphylococcus aureus from its residence in the nose decreases nosocomial infection from that organism. Wertheim and associates screened more than 17,000 nonsurgical adult patients in 4 hospitals in the Netherlands to detect those colonized with S aureus. One-quarter (4479, or 25.6%) of the patients were found to be culture-positive. Some 1600 patients survived exclusion criteria (such as presence of S aureus infection at the time of enrollment, discharge from the hospital before enrollment could be accomplished, and declining participation in the study) and were randomized to receive either mupirocin 2% nasal ointment or an odor- and appearance-matching placebo twice daily for 5 days. The presence of nosocomial S aureus infection was determined by reviewing all microbiology culture reports during and for 6 weeks after patients’ hospitalization. Few medication side effects were reported.

The results? Although the rate of nosocomial S aureus infection was slightly lower in the mupirocin group (1.9% vs 2.4%), the difference was not statistically significant. Likewise, duration of hospitalization and in-hospital mortality were similar in both groups. However, in patients who developed nosocomial S aureus infection, onset of infection was significantly delayed in the mupirocin group (median time to infection, 32 vs 13 days [P = .02]). Wertheim et al hypothesized that the delay may have resulted from post-prophylaxis S aureus recolonization of the nose from extranasal sites since it is known that recolonization may occur in 38-43% of patients 4-6 weeks after mupirocin use. They further opined that a repeat mupirocin application might lead to increased efficacy by preventing such recolonization.

Comment by Jerry D. Smilack, MD

Chronic or persistent nasal colonization by S aureus occurs in 10-20% of healthy individuals; transient or short-lived colonization occurs in up to 70-90%. Higher rates of colonization occur in hemodialysis and HIV-infected patients, among others. Given that most staphylococcal infections develop in those already colonized with the organism, it would seem reasonable to speculate that eradicating the colonizing bacteria should reduce the likelihood of infection. Because the most important locus of staphylococcal colonization is the nasal mucosa, application of an antistaphylococcal agent to the nose—and mupirocin (Bactroban®) has emerged as the agent of choice—has been investigated intensively. Several well-designed, placebo-controlled, prospective, double-blinded studies have demonstrated that nasal mupirocin can effectively reduce staphylococcal infections in hemodialysis, peritoneal dialysis, and certain other defined populations.1,2

Wertheim et al directed their attention to a different population: the nonsurgical hospitalized patient. The rationale here is that S aureus is a frequent cause of hospital-acquired infections. If these infections could be prevented, morbidity and mortality associated with hospitalization could be reduced, and both patients and the health care system in general would be the winners. From a population of more than 17,000 hospitalized patients over a 2-year period, Wertheim et al identified one-quarter with S aureus nasal colonization. After a large number of patients were excluded for what appear to have been valid exclusionary criteria, half of the remaining 1600-plus patients were then randomized to receive a 5-day treatment course of either nasal mupirocin or a placebo. S aureus infections were then identified by positive cultures for the organism over the period of hospitalization and for 6 weeks thereafter. One could quibble with this method of defining nosocomial infection. A number of patients may well have developed staphylococcal infection and not had cultures performed; their infections would have escaped detection. Wertheim et al argue that such events may well have occurred, but should have done so with equal frequency in treatment and placebo groups and should therefore not have altered their findings.

Why did this study not find a significant benefit to the use of nasal mupirocin? There are several possible explanations. Perhaps most important is that the population Wertheim et al studied was at low risk for development of the end point in question, namely nosocomial S aureus infection. Their pre-study estimate of nosocomial S aureus infection among staphylococcal nasal carriers was 6%. Their study was designed to enroll a sample size sufficient to detect a 50% reduction of infection with 80% certainty. In fact, they found the nosocomial infection rate due to S aureus to be only 2.8% in the placebo group. Therefore, a much larger group of patients would have been necessary to detect a statistically significant benefit from any intervention. It is possible that greater rates of infection would have occurred had there been more high-risk patients in the study population (for example, greater numbers of dialysis or intensive care unit patients). Other reasons for the failure to detect benefit include questions about (1) whether repeat mupirocin dosing might be helpful, and (2) whether extranasal colonization may have been an important source for staphylococcal infection. Another unanswered question is if mupirocin did, in fact, eradicate nasal colonization in the study patients. Wertheim et al did not report results of any follow-up nasal cultures in patients who received the antibacterial agent.

Even if nasal mupirocin were to have been shown to have a salutary effect, the question then becomes whether the findings are transferable to other hospitals and other types of patients. How should screening for nasal colonization be accomplished? Should it be done before hospital admission? Should it be done only in those nonsurgical patients who are at highest risk (eg, dialysis patients)? But the biggest question—the one that has prevented widespread use of mupirocin in certain surgical or other settings, where it has clearly been shown to be of benefit—is whether resistance to mupirocin will emerge with increasing usage. Substantial resistance has already been demonstrated in several studies.3,4

References

1. Tacconelli E, et al. Mupirocin prophylaxis to prevent Staphylococcus aureus infection in patients undergoing dialysis: A meta-analysis. Clin Infect Dis. 2003;37:1629-1638.

2. Raz R, et al. A 1-year trial of nasal mupirocin in the prevention of recurrent staphylococcal nasal colonization and skin infection. Arch Intern Med. 1996;156:1109-1112.

3. Miller MA, et al. Development of mupirocin resistance among methicillin-resistant Staphylococcus aureus after widespread use of nasal mupirocin ointment. Infect Control Hosp Epidemiol. 1996;17:811-813.

4. Cookson BD. The emergence of mupirocin resistance: a challenge to infection control and antibiotic prescribing practice. J Antimicrob Chemother. 1998;41:11-18.

Jerry D. Smilack, MD Infectious Disease Consultant Mayo Clinic Scottsdale Scottsdale, AZ, is Associate Editor of Infectious Disease Alert.