Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-25T01:32:04.075Z Has data issue: false hasContentIssue false
  • English
  • Français

What To Think If the Results of the National Institutes of Health Randomized Trial of Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus Control Measures Are Negative (and Other Advice to Young Epidemiologists): A Review and an Au Revoir

Published online by Cambridge University Press:  21 June 2016

Barry M. Farr
Barry M. Farr*
Affiliation:
Department of Medicine, University of Virginia Health System, Charlottesville, Virginia
*
Department of Medicine, PO Box 800473, University of Virginia Health System, Charlottesville, VA 22908, (bmf@virginia.edu)
Get access Rights & Permissions [Opens in a new window]

Extract

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infections continues to rise in National Nosocomial Infections Surveillance system hospitals, and these pathogens are reportedly causing more than 100,000 infections and many deaths each year in US healthcare facilities. This has led some to insist that control measures are now urgently needed, but several recent articles have suggested that isolation of patients does not work, is not needed, or is unsafe, or that a single cluster-randomized trial could be used to decide such matters. At least 101 studies have reported controlling MRSA infection and 38 have reported controlling VRE infection by means of active detection by surveillance culture and use of isolation for all colonized patients in healthcare settings where the pathogens are epidemic or endemic, in academic and nonacademic hospitals, and in acute care, intensive care, and long-term care settings. MRSA colonization and infection have been controlled to exceedingly low levels in multiple nations and in the state of Western Australia for decades by use of active detection and isolation. Studies suggesting problems with using such data to control MRSA colonization and infection have their own problems, which are discussed. Randomized trials are epidemiologic tools that can sometimes provide erroneous results, and they have not been considered necessary for studying isolation before it is used to control other important infections, such as tuberculosis, smallpox, and severe acute respiratory syndrome. No single epidemiologic study should be considered definitive. One should always weigh all available evidence. Infection with antibiotic-resistant pathogens such as MRSA and VRE is controllable to a low level by active detection and isolation of colonized and infected patients. Effective measures should be used to minimize the morbidity and mortality attributable to these largely preventable infections.

Type
Review Articles
Information
Infection Control & Hospital Epidemiology , Volume 27 , Issue 10 , October 2006 , pp. 1096 - 1106
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Rilke, RM. Letters to a Young Poet. New York: W.W. Norton and Company; 1934.Google Scholar
2. Shakespeare, W. The Tempest, Act V, scene I, line ~43 ff. London, 1611. in Harrison, GB, ed. Shakespeare: major plays and sonnets. New York: Harcourt Brace and World; 1984.Google Scholar
3. National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004; 32:470–485.Google Scholar
4. Klevens, RM, Edwards, JR, Tenover, FC, McDonald, LC, Horan, T, Gaynes, R; National Nosocomial Infections Surveillance System. Changes in the epidemiology of methicillin-resistant Staphylococcus aureus in intensive care units in US hospitals, 1992-2003. Clin Infect Dis 2006; 42:389–391.CrossRefGoogle ScholarPubMed
5. Abramson, MA, Sexton, DJ. Nosocomial methicillin-resistant and methicillin-susceptible Staphylococcus aureus primary bacteremia: at what costs? Infect Control Hosp Epidemiol 1999; 20:408–411.Google Scholar
6. Cheng, AF, French, GL. Methicillin-resistant Staphylococcus aureus bacteremia in Hong Kong. J Hosp Infect 1988; 12:91–101.CrossRefGoogle ScholarPubMed
7. Stone, PW, Larson, E, Kawar, LN. A systematic audit or economic evidence linking nosocomial infections and infection control interventions:1990-2000. Am J Infect Control 2002; 30:145–152.Google Scholar
8. Cosgrove, SE, Qi, Y, Kaye, KS, Harbarth, S, Karchmer, AW, Carmeli, Y. The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: mortality, length of stay, and hospital charges. Infect Control Hosp Epidemiol 2005; 26:166–174.CrossRefGoogle ScholarPubMed
9. Reed, SD, Friedman, JY, Engemann, JJ, et al. Costs and outcomes among hemodialysis-dependent patients with methicillin-resistant or methicillin-susceptible Staphylococcus aureus bacteremia. Infect Control Hosp Epidemiol 2005; 26:175–183.Google Scholar
10. McHugh, CG, Riley, LW. Risk factors and costs associated with methicillin-resistant Staphylococcus aureus bloodstream infections. Infect Control Hosp Epidemiol 2004; 25:425–430.Google Scholar
11. Stosor, V, Peterson, L, Postelnick, M, Noskin, G. Enterococcus faecium bacteremia: does vancomycin resistance make a difference? Arch Intern Med 1998; 158:522–527.Google Scholar
12. Cosgrove, SE, Sakoulas, G, Perencevich, EN, Schwaber, MJ, Karchmer, AW, Carmeli, Y. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bactermia: a meta-analysis. Clin Infect Dis 2003; 36:53–59.Google Scholar
13. Whitby, M, McLaws, ML, Berry, G. Risk of death from methicillin-resistant Staphylococcus aureus bacteraemia: a meta-analysis. Med J Aust 2001; 175:264–267.Google Scholar
14. Salgado, CD, Farr, BM. Outcomes associated with vancomycin resistant enterococci: a meta-analysis. Infect Control Hosp Epidemiol 2003; 24:690–698.CrossRefGoogle ScholarPubMed
15. DiazGranados, CA, Zimmer, SM, Klein, M, Jernigan, JA. Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis. Clin Infect Dis 2005; 41:327–333.Google Scholar
16. West, TE, Guerry, C, Hiott, M, Morrow, N, Ward, K, Salgado, CD. Effect of targeted surveillance for control of methicillin-resistant Staphylococcus aureus in a community hospital system. Infect Control Hosp Epidemiol 2006; 27:233–238.CrossRefGoogle Scholar
17. Lucet, J, Chevret, S, Durand-Zaleski, I, Chastang Cregnier, B. Prevalence and risk factors for carriage of methicillin resistant Staphylococcus aureus at admission to the intensive care unit. Arch Intern Med 2003; 163:181–188.Google Scholar
18. Bjorholt, I, Haglind, E. Cost-savings achieved by eradication of epidemic methicillin-resistant Staphylococcus aureus (EMRSA)-16 from a large teaching hospital. Eur J Clin Microbiol Infect Dis 2004; 23:688–695.Google Scholar
19. Vriens, M, Blok, H, Fluit, A, Troelstra, A, van der, WC, Verhoef, J. Costs associated with a strict policy to eradicate methicillin-resistant Staphylococcus aureus in a Dutch University Medical Center: a 10-year survey. Eur J Clin Microbiol Infect Dis 2002; 21:782–786.Google Scholar
20. Karchmer, TB, Durbin, LJ, Simonton, BM, Farr, BM. Cost-effectiveness of active surveillance cultures and contact/droplet precautions for control of methicillin-resistant Staphylococcus aureus . J Hosp Infect 2002; 51:126–132.CrossRefGoogle ScholarPubMed
21. Papia, G, Louie, M, Tralla, A, Johnson, C, Collins, V, Simor, AE. Screening high-risk patients for methicillin-resistant Staphylococcus aureus on admission to the hospital: is it cost effective? Infect Control Hosp Epidemiol 1999; 20:473–477.Google Scholar
22. Chaix, C, Durand-Zaleski, I, Alberti, C, Brun-Buisson, C. Control of endemic methicillin-resistant Staphylococcus aureus: a cost-benefit analysis in an intensive care unit. JAMA 1999;282:1745–1751.Google Scholar
23. Jernigan, JA, Clemence, MA, Stott, GA, et al. Control of methicillin resistant Staphylococcus aureus at a university hospital: one decade later. Infect Control Hosp Epidemiol 1995; 16:686–696.Google Scholar
24. Muto, CA, Giannetta, ET, Durbin, LJ, Simonton, BM, Farr, BM. Cost-effectiveness of perirectal surveillance cultures for controlling vancomycin-resistant Enterococcus . Infect Control Hosp Epidemiol 2002; 23:429–435.Google Scholar
25. Montecalvo, MA, Jarvis, WR, Uman, J, et al. Costs and savings associated with infection control measures that reduced transmission of vancomycin-resistant enterococci in an endemic setting. Infect Control Hosp Epidemiol 2001; 22:437–442.CrossRefGoogle Scholar
26. Bronstein, M, Kaye, K, Sexton, D. Gown utilization as a measure of cost of methicillin-resistant Staphylococcus aureus (MRSA) screening. In: Program and abstracts of the 12th Annual Meeting of the Society for Healthcare Epidemiology of America; April 6-9, 2002; Salt Lake City, UT. Abstract 47.Google Scholar
27. Calfee, DP, Farr, BM. Infection control and cost control in the era of managed care. Infect Control Hosp Epidemiol 2002; 23:407–410.Google Scholar
28. Strausbaugh, LJ, Siegel, JD, Weinstein, RA. Preventing transmission of multidrug-resistant bacteria in health care settings: a tale of 2 guidelines. Clin Infect Dis 2006; 42:828–835.Google Scholar
29. Salgado, CD, Farr, BM. The importance of infection control in controlling antimicrobial-resistant pathogens. In: Jarvis, WR, ed. Bennett and Brachman's Hospital Infections. 5th ed. Philadelphia: Lippincott Williams & Wilkins (in press).Google Scholar
30. Wertheim, HF, Vos, MC, Boelens, HA, et al. Low prevalence of methicillin-resistant Staphylococcus aureus (MRSA) at hospital admission in The Netherlands: the value of search and destroy and restrictive antibiotic use. J Hosp Infect 2004; 56:321–325.Google Scholar
31. Kotilainen, P, Routamaa, M, Peltonen, R, et al. Elimination of epidemic methicillin-resistant Staphylococcus aureus from a university hospital and district institutions, Finland. Emerg Infect Dis 2003; 9:169–175.Google Scholar
32. Peterson, L. Lessons to be shared in successful reductions of infections. Illinois Quality Leadership Conference- Focusing on Reducing and Eliminating Infections. Naperville, IL: Illinois Hospital Association and Metropolitan Chicago Healthcare Council; May 24, 2006.Google Scholar
33. Verbrugh, HA. Best practices from The Netherlands. In: Program and abstracts of the 2nd Infection Prevention and Control Conference: Managing MRSA—a call to action. Co-convened by the Association for Professionals in Infection Control and Epidemiology, and Joint Commission Resources. August 15, 2006; Cambridge, MA.Google Scholar
34. Cooper, BS, Stone, SP, Kibbler, CC, et al. Isolation measures in the hospital management of methicillin resistant Staphylococcus aureus (MRSA): systematic review of the literature. BMJ 2004; 329:533–538.Google Scholar
35. Cepeda, JA, Whitehouse, T, Cooper, B, et al. Isolation of patients in single rooms or cohorts to reduce spread of MRSA in intensive-care units: prospective two-centre study. Lancet 2005; 365:295–304.Google Scholar
36. Frost, WH. Epidemiology. In Maxcy, KF, ed. The Papers of Wade Hampton Frost, M.D. New York, NY: The Commonwealth Fund; 1941:493–542.Google Scholar
37. Shakespeare, W. Richard II, Act II, scene I, line ~43, ff., London; 1594.Google Scholar
38. Panum, PL. Observations Made During the Epidemic of Measles on the Faroe Islands in the Year 1846. New York: American Public Health Association; 1940.Google Scholar
39. McKay, N, Wallis, L. Rabies: a review of UK management. Emerg Med J 2005; 22:316–321.Google Scholar
40. Paul, JH, Freese, HL. Epidemiological and bacteriological study of “common cold” in isolated Arctic community (Spitsbergen). Am J Hygiene 1933; 17:517–535.Google Scholar
41. Tiemersma, EW, Monnet, DL, Bruinsma, N, Skov, R, Monen, JC, Grundmann, H. Staphylococcus aureus bacteremia, Europe. Emerg Infect Dis 2005; 11:1798–1799.Google Scholar
42. Tiemersma, EW, Bronzwaer, SL, Lyytikainen, O, et al.; European Antimicrobial Resistance Surveillance System Participants. Methicillin-resistant Staphylococcus aureus in Europe, 1999-2002. Emerg Infect Dis 2004; 10:1627–1634.Google Scholar
43. Verhoef, J, Beaujean, D, Blok, H, et al. A Dutch approach to methicillin-resistant Staphylococcus aureus . Eur J Clin Microbiol Infect Dis 1999; 18:461–466.CrossRefGoogle ScholarPubMed
44. Salmenlinna, S, Lyytikainen, O, Kotilainen, P, Scotford, R, Siren, E, Vuopio-Varkila, J. Molecular epidemiology of methicillin-resistant Staphylococcus aureus in Finland. Eur J Clin Microbiol Infect Dis 2000; 19:101–107.Google Scholar
45. Boyce, JM, Cookson, B, Christiansen, K, et al. Meticillin-resistant Staphylococcus aureus . Lancet Infect Dis 2005; 5:653–663.Google Scholar
46. Dailey, L, Coombs, GW, O'Brien, FG, et al. Methicillin-resistant Staphylococcus aureus. Western Australia. Emerg Infect Dis 2005; 11:1584–1590.Google Scholar
47. Muto, CA, Jernigan, JA, Ostrowksy, BE, et al. SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and Enterococcus . Infect Control Hosp Epidemiol 2003; 24:362–386.Google Scholar
48. Herrera, O, Rhoton, B, Cantey, J. Control of methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal intensive care unit using active surveillance: one year follow-up. In: Program and abstracts of the 13th Annual Meeting of the Society for Healthcare Epidemiology of America; April 5-8, 2003, Arlington, VA. Abstract 92.Google Scholar
49. Arnow, P, Allyn, PA, Nichols, EM, Hill, DL, Pezzlo, M, Bartlett, RH. Control of methicillin-resistant Staphylococcus aureus in a burn unit: role of nurse staffing. J Trauma 1982; 22:954–959.Google Scholar
50. Blumberg, LH, Klugman, KP. Control of methicillin-resistant Staphylococcus aureus bacteraemia in high-risk areas. Eur J Clin Microbiol Infect Dis 1994; 13:82–85.Google Scholar
51. Campbell, JR, Zaccaria, E, Mason, EO Jr, Baker, CJ. Epidemiological analysis defining concurrent outbreaks of Serratia marcescens and methicillin-resistant Staphylococcus aureus in a neonatal intensive-care unit. Infect Control Hosp Epidemiol 1998; 19:924–928.Google Scholar
52. Coello, R, Jimenez, J, Garcia, M, et al. Prospective study of infection, colonization and carriage of methicillin-resistant Staphylococcus aureus in an outbreak affecting 990 patients. Eur J Clin Microbiol Infect Dis 1994; 13:74–81.Google Scholar
53. Cosseron-Zerbib, M, Roque Afonso, AM, Naas, T, et al. A control programme for MRSA (methicillin-resistant Staphylococcus aureus) containment in a paediatric intensive care unit: evaluation and impact on infections caused by other micro-organisms. J Hosp Infect 1998; 40:225–235.Google Scholar
54. Cox, RA, Conquest, C, Mallaghan, C, Marples, RR. A major outbreak of methicillin-resistant Staphylococcus aureus caused by a new phage-type (EMRSA-16). J Hosp Infect 1995; 29:87–106.Google Scholar
55. Duckworth, GJ, Lothian, JL, Williams, JD. Methicillin-resistant Staphylococcus aureus: report of an outbreak in a London teaching hospital. J Hosp Infect 1988; 11:1–15.CrossRefGoogle Scholar
56. Girou, E, Pujade, G, Legrand, P, Cizeau, F, Brun-Buisson, C. Selective screening of carriers for control of methicillin-resistant Staphylococcus aureus (MRSA) in high-risk hospital areas with a high level of endemic MRSA. Clin Infect Dis 1998; 27:543–550.Google Scholar
57. Pfaller, MA, Wakefield, DS, Hollis, R, Frederickson, M, Evans, E, Massanari, RM. The clinical microbiology laboratory as an aid in infection control: the application of molecular techniques in epidemiologic studies of methicillin-resistant Staphylococcus aureus . Diagn Microbiol Infect Dis 1991; 14:209–217.Google Scholar
58. Linnemann, CC Jr, Mason, M, Moore, P, Korfhagen, TR, Staneck, JL. Methicillin-resistant Staphylococcus aureus: experience in a general hospital over four years. Am J Epidemiol 1982; 115:941–950.Google Scholar
59. Walsh, TJ, Vlahov, D, Hansen, SL, et al. Prospective microbiologic surveillance in control of nosocomial methicillin-resistant Staphylococcus aureus . Infect Control 1987; 8:7–14.Google Scholar
60. Wernitz, MH, Swidsinski, S, Weist, K, et al. Effectiveness of a hospital-wide selective screening programme for methicillin-resistant Staphylococcus aureus (MRSA) carriers at hospital admission to prevent hospital-acquired MRSA infections. Clin Microbiol Infect 2005; 11:457–465.Google Scholar
61. Huang, SS, Yokoe, DS, Rego, VH, et al. Impact of ICU surveillance for MRSA on bacteremia. In: Program and abstracts of the 43rd Annual Meeting of the Infectious Diseases Society of America; October 6-9, 2005; San Francisco, CA. Abstract 1074.Google Scholar
62. Blank, MK, Haas, L, Donahoe, M, Kramer, P, Muto, CA. Sustained effect in reducing methicillin-resistant Staphylococcus aureus (MRSA) hospital acquired infections (HAIs) using active MRSA surveillance cultures (MSC)—three-year follow-up. In: Program and abstracts of the 15th Annual Meeting of the Society for Healthcare Epidemiology of America; 2005; Los Angeles, California. Abstract 22.Google Scholar
63. Mishal, J, Sherer, Y, Levin, Y, Katz, D, Embon, E. Two-stage evaluation and intervention program for control of methicillin-resistant Staphylococcus aureus in the hospital setting. Scand J Infect Dis 2001; 33:498–501.Google ScholarPubMed
64. Talon, D, Vichard, P, Muller, A, Bertin, M, Jeunet, L, Bertrand, X. Modelling the usefulness of a dedicated cohort facility to prevent the dissemination of MRSA. J Hosp Infect 2003; 54:57–62.Google Scholar
65. Rao, N, Jacobs, S, Joyce, L. Cost-effective eradication of an outbreak of methicillin-resistant Staphylococcus aureus in a community teaching hospital. Infect Control Hosp Epidemiol 1988; 9:255–260.Google Scholar
66. Pan, A, Carnevale, G, Catenazzi, P, et al. Trends in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections: effect of the MRSA “search and isolate” strategy in a hospital in Italy with hyper-endemic MRSA. Infect Control Hosp Epidemiol 2005; 26:127–133.Google Scholar
67. Harberg, D. Society for Healthcare Epidemiology of America guideline approach works to control a methicillin-resistant Staphylococcus aureus outbreak. Infect Control Hosp Epidemiol 2005; 26:115–116.Google Scholar
68. Khoury, J, Jones, M, Grim, A, Dunne, WM Jr, Fraser, V. Eradication of methicillin-resistant Staphylococcus aureus from a neonatal intensive care unit by active surveillance and aggressive infection control measures. Infect Control Hosp Epidemiol 2005; 26:616–621.Google Scholar
69. Saiman, L, Cronquist, A, Wu, F, et al. An outbreak of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit. Infect Control Hosp Epidemiol 2003; 24:317–321.Google Scholar
70. Boyce, JM, Havill, NL, Kohan, C, Dumigan, DG, Ligi, CE. Do infection control measures work for methicillin-resistant Staphylococcus aureus?. Infect Control Hosp Epidemiol 2004; 25:395–401.Google Scholar
71. Tomic, V, Svetina Sorli, P, Trinkaus, D, Sorli, J, Widmer, AF, Trampuz, A. Comprehensive strategy to prevent nosocomial spread of methicillin-resistant Staphylococcus aureus in a highly endemic setting. Arch Intern Med 2004; 164:2038–2043.Google Scholar
72. Sax, H, Posfay-Barbe, K, Harbarth, S, et al. Control of a cluster of community-associated, methicillin-resistant Staphylococcus aureus in neonatology. J Hosp Infect 2006; 63:93–100.Google Scholar
73. Lucet, JC, Paoletti, X, Lolom, I, Paugam-Burtz, C, et al. Successful long-term program for controlling methicillin-resistant Staphylococcus aureus in intensive care units. Intensive Care Med 2005; 31:1051–1057.Google Scholar
74. Farrington, M, Redpath, C, Trundle, C, Coomber, S, Brown, NM. Winning the battle but losing the war: methicillin-resistant Staphylococcus aureus (MRSA) infection at a teaching hospital. QJM 1998; 91:539–548.Google Scholar
75. Boyce, JM, Mermel, LA, Zervos, MJ, et al. Controlling vancomycin-resistant enterococci. Infect Control Hosp Epidemiol 1995; 16:634–637.CrossRefGoogle ScholarPubMed
76. Boyce, JM, Opal, SM, Chow, JW, et al. Outbreak of multi-drug resistant Enterococcus faecium with transferable vanB class vancomycin resistance. J Clin Microbiol 1994; 32:1148–1153.Google Scholar
77. Livornese, LL, Dias, S, Romanowski, B, Taylor, S, et al. Hospital-acquired infection with vancomycin-resistant Enterococcus faecium transmitted by electronic thermometers. Ann Intern Med 1992; 117:112–116.Google Scholar
78. Byers, KE, Anglim, AM, Anneski, CJ, et al. A hospital epidemic of vancomycin-resistant enterococcus: risk factors and control. Infect Control Hosp Epidemiol 2001; 22:140–147.Google Scholar
79. Ostrowsky, BE, Trick, WE, Sohn, AH, et al. Control of vancomycin-resistant enterococcus in health care facilities in a region. N Engl J Med 2001;344:1427–1433.Google Scholar
80. Price, CS, Paule, S, Noskin, GA, Peterson, LR. Active surveillance reduces the incidence of vancomycin-resistant enterococcal bacteremia. Clin Infect Dis 2003; 37:921–928.Google Scholar
81. Siddiqui, AH, Harris, AD, Hebden, J, Wilson, PD, Morris, JG, Roghmann, M. The effect of active surveillance for vancomycin resistant enterococci in high risk units on vancomycin resistant enterococci incidence hospital-wide. Am J Infect Control 2002; 30:40–43.Google Scholar
82. Muto, CA, Posey, K, Blank, M, et al. Controlling vancomycin resistant enterococci (VRE) using weekly surveillance culturing (VRESC) and barrier precautions (BP): “search and destroy”. In: Program and abstracts of the 14th Annual Meeting of the Society for Healthcare Epidemiology of America; April 17-20, 2004; Philadelphia, PA. Abstract 365.Google Scholar
83. Christiansen, KJ, Tibbett, PA, Beresford, W, et al. Eradication of a large outbreak of a single strain of vanB vancomycin-resistant Enterococcus faecium at a major Australian teaching hospital. Infect Control Hosp Epidemiol 2004; 25:384–390.Google Scholar
84. Mascini, EM, Troelstra, A, Beitsma, M, et al. Genotyping and preemptive isolation to control an outbreak of vancomycin-resistant Enterococcus faecium . Clin Infect Dis 2006; 42:739–746.Google Scholar
85. Seeberg, S, Larsson, L, Welinder-Olsson, C, et al. How an outbreak of MRSA in Gothenburg was eliminated: by strict hygienic routines and massive control-culture program [in German] Lakartidningen 2002; 99:3198–3204.Google Scholar
86. Vriens, MR, Fluit, AC, Troelstra, A, Verhoef, J, Van Der Werken, C. Are MRSA more contagious than MSSA in a surgical intensive care unit. Infect Control Hosp Epidemiol 2002; 23:491–494.Google Scholar
87. Esveld, MI, de Boer, AS, Notenboom, AJ, van Pelt, W, van Leeuwen, WJ. Secondary infection with methicillin resistant Staphylococcus aureus in Dutch hospitals (July 1994–June 1996) [in Dutch]. Nederlands Tijd-schrift voor Geneeskunde 1999; 143:205–208.Google Scholar
88. Hill, AB. A Short Textbook of Medical Statistics. Vol 11. London: Hodder and Stoughton, 1984.Google Scholar
89. Jernigan, JA, Titus, MG, Groschel, DHM, Getchell-White, SI, Farr, BM. Effectiveness of contact isolation during a hospital outbreak of methicillin-resistant Staphylococcus aureus . Am J Epidemiol 1996; 143:496–504.Google Scholar
90. Bager, F. DANMAP 98—Consumption of antimicrobial agents and occurrence of antimicrobials in bacteria from food animals, food and humans in Denmark. 1999. Available at: http://www.danmap.org.. Accessed September 10, 2006.Google Scholar
91. Sommer, A. SARS: paradigm for an emerging pathogen in a global community. Paper presented at the 14th Annual Meeting of the Society for Healthcare Epidemiology of America; April 17-20, 2004; Philadelphia, PA.Google Scholar
92. Seto, WH, Tsang, D, Yung, RW, et al.; Advisors of Expert SARS group of Hospital Authority. Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS). Lancet 2003; 361:1519–1520.Google Scholar
93. Lipsitch, M, Cohen, T, Cooper, B, et al. Transmission dynamics and control of severe acute respiratory syndrome. Science 2003; 300:1966–1970.Google Scholar
94. Beck-Sague, CM, Dooley, SW, et al. Outbreak of multidrug-resistant tuberculosis among persons with HIV infection in an urban hospital: transmission to staff and patients and control measures. JAMA 1992; 268:1280–1286.Google Scholar
95. Thompson, RL, Cabezudo, I, Wenzel, RP. Epidemiology of nosocomial infections caused by methicillin-resistant Staphylococcus aureus . Ann Intern Med 1982; 97:309–317.CrossRefGoogle ScholarPubMed
96. Perencevich, EN, Fisman, DN, Lipsitch, M, Harris, AD, Morris, JG, Smith, D. Projected benefits of active surveillance for vancomycin resistant enterococci in ICU settings. Clin Infect Dis 2004;38:1108–1115.Google Scholar
97. Netto dos Santos, KR, de Souza, FL, Gontijo Filho, PP. Emergence of high-level mupirocin resistance in methicillin-resistant Staphylococcus aureus isolated from Brazilian university hospitals. Infect Control Hosp Epidemiol 1996; 17:813–816.Google Scholar
98. Miller, MA, Dascal, A, Portnoy, J, Mendelson, J. Development of mupirocin resistance among methicillin-resistant Staphylococcus aureus after widespread use of nasal mupirocin ointment. Infect Control Hosp Epidemiol 1996; 17:811–813.Google Scholar
99. Vasquez, JE, Walker, ES, Franzus, BW, Overbay, BK, Reagan, DR, Sarubbi, FA. The epidemiology of mupirocin resistance among methicillin-resistant Staphylococcus aureus at a Veterans' Affairs hospital. Infect Control Hosp Epidemiol 2000; 21:459–464.Google Scholar
100. Goldmann, D. System failure versus personal accountability—the case for clean hands. N Engl J Med 2006; 355:121–123.Google Scholar
101. Harbarth, S, Masuet-Aumatell, C, Schrenzel, J, et al. Evaluation of rapid screening and pre-emptive contact isolation for detecting and controlling methicillin-resistant Staphylococcus aureus in critical care: an interventional cohort study. Crit Care 2006; 10:R25.Google Scholar
102. Farr, BM. The state of the science. Am J Infect Control 2004; 32:106–113.Google Scholar
103. Faoagali, JL, Thong, ML, Grant, D. Ten years' experience with methicillin-resistant Staphylococcus aureus in a large Australian hospital. J Hosp Infect 1992; 20:113–119.Google Scholar
104. Salgado, CD, Farr, BM. What proportion of hospital patients colonized with methicillin-resistant Staphylococcus aureus are identified by clinical microbiology cultures? Infect Control Hosp Epidemiol 2006; 27:116–121.Google Scholar
105. Back, NA, Linnemann, CC Jr, Staneck, JL, Kotagal, UR. Control of methicillin-resistant Staphylococcus aureus in a neonatal intensive-care unit: use of intensive microbiologic surveillance and mupirocin. Infect Control Hosp Epidemiol 1996; 17:227–231.Google Scholar
106. Fekety, FF. The epidemiology and prevention of staphylococcal infection. Medicine 1964; 43:593–613.Google Scholar
107. Huang, YC, Su, LH, Wu, TL, Lin, TY. Molecular surveillance of clinical methicillin-resistant Staphylococcus aureus isolates in neonatal intensive care units. Infect Control Hosp Epidemiol 2005; 26:157–160.Google Scholar
108. Haley, RW, Cushion, NB, Tenover, FC, et al. Eradication of endemic methicillin-resistant Staphylococcus aureus infections from a neonatal intensive care unit. J Infect Dis 1995; 171:614–624.Google Scholar
109. Gerber, SI, Jones, RC, Scott, MV, et al. Management of outbreaks of methicillin-resistant Staphylococcus aureus infection in the neonatal intensive care unit: a consensus statement. Infect Control Hosp Epidemiol 2006; 27:139–145.Google Scholar
110. Revised guidelines for the control of methicillin-resistant Staphylococcus aureus infection in hospitals. British Society for Antimicrobial Chemotherapy, Hospital Infection Society and the Infection Control Nurses Association. J Hosp Infect 1998; 39:253–290.Google Scholar
111. Wilson, APR, Bellingan, G, Singer, M. Isolation of patients with MRSA infection. Lancet 2005; 365:1304–1305.Google Scholar
112. Poutanen, SM, Vearncombe, M, McGeer, AJ, Gardam, M, Large, G, Simor, AE. Nosocomial acquisition of methicillin-resistant Staphylococcus aureus during an outbreak of severe acute respiratory syndrome. Infect Control Hosp Epidemiol 2005; 26:134–137.Google Scholar
113. Maki, DG, McCormick, RD, Zilz, MA, Stolz, SM, Alvarado, CJ. An MRSA outbreak in a SICU during universal precautions: new epidemiology for nosocomial MRSA; downside for universal precautions. In: Program and abstracts of the 3rd Decennial International Conference on Nosocomial Infections. Atlanta: Centers for Disease Control and Prevention; 1990:26.Google Scholar
114. Yap, FH, Gomersall, CD, Fung, KS, et al. Increase in methicillin-resistant Staphylococcus aureus acquisition rate and change in pathogen pattern associated with an outbreak of severe acute respiratory syndrome. Clin Infect Dis 2004; 39:511–516.Google Scholar
115. Sherertz, RJ, Reagan, DR, Hampton, KD, et al. A cloud adult: the Staphylococcus aureus-virus interaction revisited. Ann Intern Med 1996; 124:539–547.Google Scholar
116. Suh, HK, Jeon, YH, Song, JS, Hwang, SJ, Cheong, HJ. A molecular epidemiologic study of methicillin-resistant Staphylococcus aureus infection in patients undergoing middle ear surgery. Eur Arch Oto-Rhino-Laryngol 1998; 255:347–351.Google Scholar
117. Blok, HE, Troelstra, A, Kamp-Hopmans, TE, et al. Role of healthcare workers in outbreaks of methicillin-resistant Staphylococcus aureus: a 10-year evaluation from a Dutch university hospital. Infect Control Hosp Epidemiol 2003; 24:679–185.Google Scholar
118. Salgado, C, Nobels, D, Ruisz, M, et al. Control of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) using active surveillance cultures and contact precautions. In: Program and abstracts of the 14th Annual Meeting of the Society for Healthcare Epidemiology of America; April 17-20, 2004; Philadelphia, PA. Abstract 41.Google Scholar
119. Salgado, CD, Nobels, D, Ruisz, M, et al. Effect of active surveillance cultures and contact precautions for controlling endemic vancomycin-resistant Enterococcus . In: Program and abstracts of the 14th Annual Meeting of the Society for Healthcare Epidemiology of America; April 17-20, 2004; Philadelphia, PA. Abstract 364.Google Scholar
120. Nijssen, S, Bonten, MJ, Weinstein, RA. Are active microbiological surveillance and subsequent isolation needed to prevent the spread of methicillin-resistant Staphylococcus aureus?. Clin Infect Dis 2005; 40:405–409.Google Scholar
121. Marshall, C, Harrington, G, Wolfe, R, Fairley, CK, Wesselingh, S, Spelman, D. Acquisition of methicillin-resistant Staphylococcus aureus in a large intensive care unit. Infect Control Hosp Epidemiol 2003; 24:322–326.Google Scholar
122. Grundmann, H, Aires-de-Sousa, M, Boyce, J, Tiemersma, E. Emergence and resurgence of methicillin-resistant Staphylococcus aureus as a public-health threat. Lancet 2006; 368:874–885.Google Scholar
123. Stelfox, HT, Bates, DW, Redelmeier, DA. Safety of patients isolated for infection control. JAMA 2003; 290:1899–1905.Google Scholar
124. ClinicalTrials.gov. Hand hygiene: strategies to reduce transmission of antimicrobial resistant bacteria in intensive care units. Available at: http://clinicaltrials.gov/ct/show/NCT00100386?order=1. Accessed April 13, 2006.Google Scholar
125. Siegel, J, Strausbaugh, L, Jackson, M, Rhinehart, E, Chiarello, L, Healthcare Practices Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. Draft guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings. June, 2004. Available at: http://www.premierinc.com/all/safety/resources/guidelines/cdc_guidelines.jsp. Accessed September 11, 2005.Google Scholar
126. Concato, J, Shah, N, Horwitz, RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. New Engl J Med 2000; 342:1887–1892.Google Scholar
127. Benson, K, Hartz, AJ. A comparison of observational studies and randomized, controlled trials. New Engl J Med 2000; 342:1878–1886.Google Scholar
128. Last, JM. A dictionary of edpidemiology. 2nd ed. Oxford: Oxford University Press; 1988.Google Scholar
129. Eby, GA, Davis, DR, Halcomb, WW. Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother 1984; 25:20–24.Google Scholar
130. Karlowski, TR, Chalmers, TC, Frenkel, LD, Kapikian, AZ, Lewis, TL, Lynch, JM. Ascorbic acid for the common cold: a prophylactic and therapeutic trial. JAMA 1975; 231:1038–1042.Google Scholar
131. Farr, BM, Gwaltney, JM Jr. The problems of taste in placebo matching: zinc gluconate for the common cold. J Chronic Dis 1987; 40:875–879.Google Scholar
132. Farr, BM, Conner, EM, Betts, RF, Oleske, J, Minnefor, A, Gwaltney, JM Jr. Two randomized controlled trials of zinc gluconate lozenge therapy of experimentally induced rhinovirus colds. Antimicrob Agents Chemother 1987;31:1183–1187.Google Scholar
133. da Silva Coimbra, MV, Silva-Carvalho, MC, Wisplinghoff, H, et al. Clonal spread of methicillin-resistant Staphylococcus aureus in a large geographic area of the United States. J Hosp Infect 2003; 53:103–110.Google Scholar
134. Morris, JG, Shay, DK, Hebden, JN, et al. Enterococci resistant to multiple antimicrobial agents including vancomycin: establishment of endemicity in a university medical center. Ann Intern Med 1995; 123:250–259.Google Scholar
135. Slaughter, S, Hayden, MK, Nathan, C, et al. A comparison of the effect of universal use of gloves and gowns with that of glove use alone on acquisition of vancomycin-resistant enterococci in a medical intensive care unit. Ann Intern Med 1996; 125:448–456.Google Scholar
136. Warren, DK, Kollef, MH, Seiler, SM, Fridkin, SK, Fraser, VJ. The epidemiology of vancomycin-resistant Enterococcus colonization in a medical intensive care unit. Infect Control Hosp Epidemiol 2003; 24:257–263.Google Scholar