Mupirocin Prophylaxis against Nosocomial Staphylococcus aureus Infections in Nonsurgical Patients

A Randomized Study

  1. Heiman F.L. Wertheim, MD, MSc;
  2. Margreet C. Vos, MD, PhD;
  3. Alewijn Ott, MD, PhD;
  4. Andreas Voss, MD, PhD;
  5. Jan A.J.W. Kluytmans, MD, PhD;
  6. Christina M.J.E. Vandenbroucke-Grauls, MD, PhD;
  7. Marlene H.M. Meester, ICP;
  8. Peter H.J. van Keulen, MD; and
  9. Henri A. Verbrugh, MD, PhD
  1. From Erasmus University Medical Center, Rotterdam, the Netherlands; University Medical Center St. Radboud, Nijmegen, the Netherlands; Amphia Hospital, Breda, the Netherlands; and VU University Medical Center, Amsterdam, the Netherlands.

    Abstract

    Background: Staphylococcus aureus nasal carriage is a major risk factor for nosocomial S. aureus infection. Studies show that intranasal mupirocin can prevent nosocomial surgical site infections. No data are available on the efficacy of mupirocin in nonsurgical patients.

    Objective: To assess the efficacy of mupirocin prophylaxis in preventing nosocomial S. aureus infections in nonsurgical patients.

    Design: Randomized, double-blind, placebo-controlled trial.

    Setting: 3 tertiary care academic hospitals and 1 nonacademic hospital.

    Patients: 1602 culture-proven S. aureus carriers hospitalized in nonsurgical departments.

    Intervention: Therapy with mupirocin 2% nasal ointment (n = 793) or placebo ointment (n = 809), twice daily for 5 days, started 1 to 3 days after admission.

    Measurements: Nosocomial S. aureus infections according to defined criteria, in-hospital mortality, duration of hospitalization, and time to nosocomial S. aureus infection. Staphylococcus aureus isolates were genotyped to assess whether infection was caused by endogenous strains.

    Results: The mupirocin and placebo groups did not statistically differ in the rates of nosocomial S. aureus infections (mupirocin, 2.6%; placebo, 2.8%; risk difference, 0.2 percentage point [95% CI, −1.5 to 1.9 percentage points]), mortality (mupirocin, 3.0%; placebo, 2.8%; risk difference, −0.2 percentage point [CI, −1.9 to 1.5 percentage points]), or duration of hospitalization (median for both, 8 days). However, time to nosocomial S. aureus infection was decreased in the mupirocin group from 12 to 25 days (P > 0.2). A total of 77% of S. aureus nosocomial infections were endogenous.

    Limitations: A few infections in both groups may have been missed because investigators assessed a patient for infection only if microbiology culture results were positive for S. aureus.

    Conclusion: Routine culture for S. aureus nasal carriage at admission and subsequent mupirocin application does not provide effective prophylaxis against nosocomial S. aureus infections in nonsurgical patients.

    Article and Author Information

    • Acknowledgments: The authors thank all the patients who participated in this study and the following people who have made this study possible: Annie Antonissen; Myra Behrendt; Alex van Belkum; Hélène Boelens; Wilma Kraak; Jan Nouwen; Gerard Parlevliet; Cindy van Pelt; Geert van de Sanden; Melanie Srodzinsky; Roel Verkooyen; Laura Verputten; Arjen van Vliet; Joke van Wegen; and the technicians and infection control nurses at Erasmus Medical Center, Amphia Hospital, University Medical Center St. Radboud, and VU Medical Center.

    • Grant Support: By Zon-Mw, The Netherlands Organization for Health Research and Development.

    • Potential Financial Conflicts of Interest:Grants received: J.A.J.W. Kluytmans (GlaxoSmithKline).

    • Requests for Single Reprint: Heiman F.L. Wertheim, MD, MSc, Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands; e-mail, h.wertheim{at}erasmusmc.nl.

    • Current Author Addresses: Drs. Wertheim, Vos, Ott, and Verbrugh: Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands.

    • Dr. Voss: University Medical Center St. Radboud, Department of Medical Microbiology and Infectious Diseases, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, the Netherlands.

    • Drs. Kluytmans and van Keulen: Amphia Hospital Breda, Langendijk, Laboratory of Microbiology and Infection Control, PO Box 90158, 4800 RK Breda, the Netherlands.

    • Dr. Vandenbroucke-Grauls and Ms. Meester: Department of Medical Microbiology and Infection Prevention, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.

    • Author Contributions: Conception and design: H.F.L. Wertheim, M.C. Vos, A. Ott, A. Voss, J.A.J.W. Kluytmans, C.M.J.E. Vandenbroucke-Grauls, P.H.J. van Keulen, H.A. Verbrugh.

    • Analysis and interpretation of the data: H.F.L. Wertheim, M.C. Vos, A. Ott, A. Voss, J.A.J.W. Kluytmans, C.M.J.E. Vandenbroucke-Grauls, M.H.M. Meester, P.H.J. van Keulen, H.A. Verbrugh.

    • Drafting of the article: H.F.L. Wertheim, M.C. Vos, A. Ott, H.A. Verbrugh.

    • Critical revision of the article for important intellectual content: M.C. Vos, A. Ott, A. Voss, J.A.J.W. Kluytmans, C.M.J.E. Vandenbroucke-Grauls, M.H.M. Meester, P.H.J. van Keulen, H.A. Verbrugh.

    • Final approval of the article: H.F.L. Wertheim, M.C. Vos, A. Ott, A. Voss, C.M.J.E. Vandenbroucke-Grauls, P.H.J. van Keulen, H.A. Verbrugh.

    • Provision of study materials or patients: H.F.L. Wertheim, J.A.J.W. Kluytmans, C.M.J.E. Vandenbroucke-Grauls, M.H.M. Meester, P.H.J. van Keulen.

    • Statistical expertise: H.F.L. Wertheim, A. Ott, J.A.J.W. Kluytmans.

    • Obtaining of funding: M.C. Vos, J.A.J.W. Kluytmans, P.H.J. van Keulen, H.A. Verbrugh.

    • Administrative, technical, or logistic support: H.F.L. Wertheim, J.A.J.W. Kluytmans, P.H.J. van Keulen.

    • Collection and assembly of data: H.F.L. Wertheim, A. Voss, J.A.J.W. Kluytmans, M.H.M. Meester, P.H.J. van Keulen.

    Summary for Patients

    • Summaries for Patients:Effects of Antibiotic Nose Ointment for Hospitalized Patients with Staphylococcus aureus Ann Intern Med March 16, 2004 140:I-36
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    1. Ann Intern Med March 16, 2004 vol. 140 no. 6 419-425
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