Correspondence

Intranasal Mupirocin to Prevent Postoperative Infections

N Engl J Med 2002; 347:1207-1208October 10, 2002

Article

To the Editor:

Perl et al. (June 13 issue)1 report that prophylaxis with mupirocin did not reduce the overall rate of Staphylococcus aureus infections at surgical sites but did significantly reduce the rate of nosocomial S. aureus infections. Although the surgical characteristics of the patients are indicated, there are no data on the risk factors in the two groups for bloodstream infections (e.g., the number of days of catheterization) or lower respiratory tract infections (e.g., ventilator use).2 These data would be useful for the analysis. In addition, it would be interesting to have the surgical characteristics stratified for the patients in whom nosocomial infections developed.

The authors discuss whether prophylactic use of mupirocin might lead to widespread resistance. Low-level resistance and high-level resistance to mupirocin occur, with different underlying molecular mechanisms and different clinical effects. Information about the range of activity of mupirocin against the resistant isolates would be of interest, as would the minimal-inhibitory-concentration values for the single isolates in relation to previous use of mupirocin.3 The authors mention that previous studies, including our study, demonstrated that the risk of nosocomial infections of both the bloodstream and the lower respiratory tract is higher among patients who carry S. aureus in their nares. This was not the intention of our study, since we did not determine the risk but focused on nasal carriage as the source of S. aureus bacteremia.4

Christof von Eiff, M.D.
Frank Kipp, M.D.
Karsten Becker, M.D.
University of Muenster, 48149 Muenster, Germany
eiffc@uni-muenster.de

4 References

1. 1

   Perl TM, Cullen JJ, Wenzel RP, et al. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. N Engl J Med 2002;346:1871-1877
   Full Text | Web of Science | Medline

2. 2

   de Irala-Estevez J, Martinez-Concha D, Diaz-Molina C, Masa-Calles J, Serrano del Castillo A, Fernandez-Crehuet Navajas R. Comparison of different methodological approaches to identify risk factors of nosocomial infection in intensive care units. Intensive Care Med 2001;27:1254-1262
   CrossRef | Web of Science | Medline

3. 3

   Mehtar S. New strategies for the use of mupirocin for the prevention of serious infection. J Hosp Infect 1998;40:Suppl B:S39-S44
   CrossRef | Web of Science | Medline

4. 4

   von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. N Engl J Med 2001;344:11-16
   Full Text | Web of Science | Medline

To the Editor:

Perl et al. state, “Patients in the two groups were similar.” We disagree. The mupirocin group in the total population and the S. aureus carriers who received mupirocin were more likely to have a National Nosocomial Infection Surveillance System (NNIS) risk index of 0 than were the respective placebo groups: 19.0 percent vs. 16.1 percent (odds ratio, 1.22; 95 percent confidence interval, 1.02 to 1.44; P=0.03) and 23.2 percent vs. 16.6 percent (odds ratio, 1.52; 95 percent confidence interval, 1.07 to 2.17; P=0.02), respectively. A Wilcoxon rank-sum test of the differences in the NNIS index between the mupirocin and placebo groups in the total population and the mupirocin and placebo groups among the S. aureus carriers also shows statistically significant differences (P<0.001 for both comparisons). The NNIS index has been shown to be an important predictor of the development of surgical-site infection or other nosocomial infections.1 There appears to be a systematic bias in the study, whereby the mupirocin group was significantly less likely than the placebo group to have a higher NNIS index, and there were significantly fewer S. aureus carriers in the antibiotic group than in the placebo group among the patients with a higher NNIS index. This means that the finding that mupirocin significantly decreased the rate of all nosocomial S. aureus infections among the patients who were S. aureus carriers is disputable.

Jorge E. Delgado-Hachmeister, M.D.
Edward A. Graviss, Ph.D., M.P.H.
Baylor College of Medicine, Houston, TX 77030-3498
egraviss@bcm.tmc.edu

1 References

1. 1

   Culver DH, Horan TC, Gaynes RP, et al. Surgical wound infection rates by wound class, operative procedure, and patient risk index. Am J Med 1991;91:Suppl 3B:3B-152S
   CrossRef | Web of Science

Author/Editor Response

The authors reply:

To the Editor: The goal of our randomized trial was to evaluate the effect of prophylaxis with intranasal mupirocin in surgical patients. Among the 891 patients with S. aureus nasal colonization, documented S. aureus nosocomial infections developed in only 51; 42 of these infections involved the surgical site and 9 involved other sites. We agree with von Eiff and colleagues that identifying risk factors in the patients with nosocomial infections involving sites other than the surgical site would be interesting. However, the small number of patients with S. aureus infections at nonsurgical sites limits further analyses. Von Eiff and colleagues also raise an interesting question about the clinical implications of high-level versus low-level resistance to mupirocin, which we cannot address with three isolates. The prospective study that von Eiff and colleagues performed allowed them to show that S. aureus nasal carriage was the source of S. aureus bloodstream infections.1 We did not intend to misrepresent their findings; however, in epidemiologic terms, S. aureus nasal carriage could be considered a risk factor for infection.

Delgado-Hachmeister and Graviss suggest that, on the basis of the NNIS risk index, the patients in the mupirocin and placebo groups were dissimilar. The comparison of the groups with respect to the percentage of subjects with an NNIS risk index of 0 is correct. However, the P values calculated with the use of the Wilcoxon rank-sum test that are cited by Delgado-Hachmeister and Graviss differ from the exact P values we calculated with the Wilcoxon rank-sum test when comparing the NNIS index between the mupirocin and placebo groups (P=0.34 for the intention-to-treat population and P=0.06 for the nasal carriers). We dispute their suggestion that this difference alters our finding that mupirocin significantly decreases the rate of nosocomial S. aureus infection. Our logistic regression adjusted for the effect of potential confounding variables: treatment with placebo versus mupirocin, the presence or absence of S. aureus nasal carriage, the NNIS index, and the presence or absence of renal disease, preoperative antibiotic use, and postoperative antibiotic use. That analysis showed that the risk of nosocomial S. aureus infection among nasal carriers who received mupirocin was significantly lower than the risk among those who received placebo (odds ratio, 0.50; 95 percent confidence interval, 0.28 to 0.91; P=0.02).

Trish M. Perl, M.D.
Johns Hopkins University, Baltimore, MD 21287
tperl@jhmi.edu

M. Bridget Zimmerman, Ph.D.
University of Iowa, Iowa City, IA 52242

1 References

1. 1

   von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. N Engl J Med 2001;344:11-16
   Full Text | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Lisa S. Young, Lisa G. Winston. (2006) Preoperative Use of Mupirocin for the Prevention of Healthcare‐Associated Staphylococcus aureus Infections: A Cost‐Effectiveness Analysis • . Infection Control and Hospital Epidemiology 27:12, 1304-1312
   CrossRef