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Clostridium difficile infection: Prevention and control

L Clifford McDonald, MD
Preeta K Kutty, MD, MPH
Section Editors
Stephen B Calderwood, MD
Sheldon L Kaplan, MD
Deputy Editor
Elinor L Baron, MD, DTMH


Clostridium difficile is the causative organism of antibiotic-associated colitis. It is the most common infectious cause of healthcare-associated diarrhea and a significant cause of morbidity and mortality among hospitalized patients [1]. Most cases of C. difficile infection (CDI) in the United States are associated with inpatient or outpatient contact with a healthcare setting [2-4].

Development of CDI usually requires two events: disruption of the fecal microbiota (typically via exposure to antibiotics) and ingestion of spores via the fecal-oral route. C. difficile may be shed into the environment by individuals who are infected or colonized. High rates of colonization may occur among hospitalized adults, nursing home residents, and healthy infants [5-7].

C. difficile spores can be transmitted between patients via environmental surfaces and contaminated hands of healthcare personnel [8]. Thus, efforts to prevent CDI must focus on two goals: reducing patient susceptibility to CDI and preventing organism transmission [9]. Prevention of C. difficile transmission is especially challenging because the organism forms spores that can persist on environmental surfaces for months and are resistant to commonly used cleaning agents and alcohol-based hand gels [10].

Issues related to CDI prevention and control will be reviewed here. The pathophysiology, epidemiology, clinical manifestations, and treatment of CDI are discussed separately. (See related topics.)


Preventing an initial episode — Strategies for preventing an initial episode of C. difficile infection include:

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Literature review current through: Nov 2017. | This topic last updated: Jul 25, 2017.
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  1. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015; 372:825.
  2. Jury LA, Sitzlar B, Kundrapu S, et al. Outpatient healthcare settings and transmission of Clostridium difficile. PLoS One 2013; 8:e70175.
  3. Centers for Disease Control and Prevention (CDC). Vital signs: preventing Clostridium difficile infections. MMWR Morb Mortal Wkly Rep 2012; 61:157.
  4. Chitnis AS, Holzbauer SM, Belflower RM, et al. Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med 2013; 173:1359.
  5. McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989; 320:204.
  6. Larson HE, Barclay FE, Honour P, Hill ID. Epidemiology of Clostridium difficile in infants. J Infect Dis 1982; 146:727.
  7. Riggs MM, Sethi AK, Zabarsky TF, et al. Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents. Clin Infect Dis 2007; 45:992.
  8. Loo VG, Bourgault AM, Poirier L, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med 2011; 365:1693.
  9. Dubberke ER, Carling P, Carrico R, et al. Strategies to prevent Clostridium difficile infections in acute care hospitals: 2014 Update. Infect Control Hosp Epidemiol 2014; 35:628.
  10. Gerding DN, Muto CA, Owens RC Jr. Measures to control and prevent Clostridium difficile infection. Clin Infect Dis 2008; 46 Suppl 1:S43.
  11. Leung DY, Kelly CP, Boguniewicz M, et al. Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. J Pediatr 1991; 118:633.
  12. Warny M, Vaerman JP, Avesani V, Delmée M. Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infect Immun 1994; 62:384.
  13. Aboudola S, Kotloff KL, Kyne L, et al. Clostridium difficile vaccine and serum immunoglobulin G antibody response to toxin A. Infect Immun 2003; 71:1608.
  14. Kotloff KL, Wasserman SS, Losonsky GA, et al. Safety and immunogenicity of increasing doses of a Clostridium difficile toxoid vaccine administered to healthy adults. Infect Immun 2001; 69:988.
  15. Sougioultzis S, Kyne L, Drudy D, et al. Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea. Gastroenterology 2005; 128:764.
  16. Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med 2010; 362:197.
  17. Carignan A, Poulin S, Martin P, et al. Efficacy of Secondary Prophylaxis With Vancomycin for Preventing Recurrent Clostridium difficile Infections. Am J Gastroenterol 2016; 111:1834.
  18. Van Hise NW, Bryant AM, Hennessey EK, et al. Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents. Clin Infect Dis 2016; 63:651.
  19. Shim JK, Johnson S, Samore MH, et al. Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea. Lancet 1998; 351:633.
  20. Villano SA, Seiberling M, Tatarowicz W, et al. Evaluation of an oral suspension of VP20621, spores of nontoxigenic Clostridium difficile strain M3, in healthy subjects. Antimicrob Agents Chemother 2012; 56:5224.
  21. Gerding DN, Meyer T, Lee C, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA 2015; 313:1719.
  22. Brown KA, Jones M, Daneman N, et al. Importation, Antibiotics, and Clostridium difficile Infection in Veteran Long-Term Care: A Multilevel Case-Control Study. Ann Intern Med 2016; 164:787.
  23. Centers for Disease Control and Prevention. Laboratory-identified Multidrug-Resistant Organism (MDRO) & Clostridium difficile Infection (CDI) Events for Long-term Care Facilities (LTCFs). https://www.cdc.gov/nhsn/pdfs/ltc/ltcf-labid-event-protocol_current.pdf (Accessed on December 19, 2016).
  24. Centers for Medicare & Medicaid Services. Medicare program; hospital inpatient prospective payment systems for acute care hospitals and the long-term care hospital prospective payment system and FY 2012 rates; hospitals’ FTE resident caps for. US Department of Health and Human Services, Baltimore, MD 2011.
  25. Centers for Disease Control and Prevention. Operational Guidance for Long Term Care Hospitals* to Report Facility-Wide Inpatient (FacWideIN) Clostridium difficile Infection (CDI) Laboratory-Identified (LabID) Event Data to CDC’s NHSN for the Purpose of Fulfilling CMS’s Long Term Care Hospital Quality Reporting Requirements. https://www.cdc.gov/nhsn/pdfs/cms/ltac/ltch-cdi-op-guidance.pdf (Accessed on December 19, 2016).
  26. Centers for Disease Control and Prevention. Operational Guidance for Inpatient Rehabilitation Facilities to Report Clostridium difficile Infection (CDI) Laboratory-Identified (LabID) Event Data to CDC’s NHSN for the Purpose of Fulfilling CMS’s Quality Reporting Program Requirements. https://www.cdc.gov/nhsn/pdfs/cms/irfs/irf-cdi-op-guidance.pdf (Accessed on December 19, 2016).
  27. Centers for Disease Control and Prevention. The Targeted Assessment for Prevention (TAP) Strategy. https://www.cdc.gov/hai/prevent/tap.html (Accessed on December 19, 2016).
  28. Johnson S, Gerding DN, Olson MM, et al. Prospective, controlled study of vinyl glove use to interrupt Clostridium difficile nosocomial transmission. Am J Med 1990; 88:137.
  29. Landelle C, Verachten M, Legrand P, et al. Contamination of healthcare workers' hands with Clostridium difficile spores after caring for patients with C. difficile infection. Infect Control Hosp Epidemiol 2014; 35:10.
  30. Bobulsky GS, Al-Nassir WN, Riggs MM, et al. Clostridium difficile skin contamination in patients with C. difficile-associated disease. Clin Infect Dis 2008; 46:447.
  31. Bettin K, Clabots C, Mathie P, et al. Effectiveness of liquid soap vs. chlorhexidine gluconate for the removal of Clostridium difficile from bare hands and gloved hands. Infect Control Hosp Epidemiol 1994; 15:697.
  32. Boyce JM, Pittet D, Healthcare Infection Control Practices Advisory Committee, HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Guideline for Hand Hygiene in Health-Care Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America. MMWR Recomm Rep 2002; 51:1.
  33. Jabbar U, Leischner J, Kasper D, et al. Effectiveness of alcohol-based hand rubs for removal of Clostridium difficile spores from hands. Infect Control Hosp Epidemiol 2010; 31:565.
  34. Oughton MT, Loo VG, Dendukuri N, et al. Hand hygiene with soap and water is superior to alcohol rub and antiseptic wipes for removal of Clostridium difficile. Infect Control Hosp Epidemiol 2009; 30:939.
  35. Kundrapu S, Sunkesula V, Jury I, et al. A randomized trial of soap and water hand wash versus alcohol hand rub for removal of Clostridium difficile spores from hands of patients. Infect Control Hosp Epidemiol 2014; 35:204.
  36. Edmonds SL, Zapka C, Kasper D, et al. Effectiveness of hand hygiene for removal of Clostridium difficile spores from hands. Infect Control Hosp Epidemiol 2013; 34:302.
  37. Dubberke ER, Reske KA, Noble-Wang J, et al. Prevalence of Clostridium difficile environmental contamination and strain variability in multiple health care facilities. Am J Infect Control 2007; 35:315.
  38. Samore MH, Venkataraman L, DeGirolami PC, et al. Clinical and molecular epidemiology of sporadic and clustered cases of nosocomial Clostridium difficile diarrhea. Am J Med 1996; 100:32.
  39. Kim KH, Fekety R, Batts DH, et al. Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic-associated colitis. J Infect Dis 1981; 143:42.
  40. Savage AM, Alford RH. Nosocomial spread of Clostridium difficile. Infect Control 1983; 4:31.
  41. Brooks SE, Veal RO, Kramer M, et al. Reduction in the incidence of Clostridium difficile-associated diarrhea in an acute care hospital and a skilled nursing facility following replacement of electronic thermometers with single-use disposables. Infect Control Hosp Epidemiol 1992; 13:98.
  42. Kaatz GW, Gitlin SD, Schaberg DR, et al. Acquisition of Clostridium difficile from the hospital environment. Am J Epidemiol 1988; 127:1289.
  43. Mayfield JL, Leet T, Miller J, Mundy LM. Environmental control to reduce transmission of Clostridium difficile. Clin Infect Dis 2000; 31:995.
  44. Selected EPA-registered disinfectants: List K--EPA’s registered antimicrobial products effective against Clostridium difficile spores. http://epa.gov/oppad001/chemregindex.htm (Accessed on February 28, 2014).
  45. Wilcox MH, Fawley WN, Wigglesworth N, et al. Comparison of the effect of detergent versus hypochlorite cleaning on environmental contamination and incidence of Clostridium difficile infection. J Hosp Infect 2003; 54:109.
  46. Simor AE, Bradley SF, Strausbaugh LJ, et al. Clostridium difficile in long-term-care facilities for the elderly. Infect Control Hosp Epidemiol 2002; 23:696.
  47. Ray AJ, Deshpande A, Fertelli D, et al. A Multicenter Randomized Trial to Determine the Effect of an Environmental Disinfection Intervention on the Incidence of Healthcare-Associated Clostridium difficile Infection. Infect Control Hosp Epidemiol 2017; 38:777.
  48. Vajravelu RK, Guerrero DM, Jury LA, Donskey CJ. Evaluation of stethoscopes as vectors of Clostridium difficile and methicillin-resistant Staphylococcus aureus. Infect Control Hosp Epidemiol 2012; 33:96.
  49. Manian FA, Meyer L, Jenne J. Clostridium difficile contamination of blood pressure cuffs: a call for a closer look at gloving practices in the era of universal precautions. Infect Control Hosp Epidemiol 1996; 17:180.
  50. Jernigan JA, Siegman-Igra Y, Guerrant RC, Farr BM. A randomized crossover study of disposable thermometers for prevention of Clostridium difficile and other nosocomial infections. Infect Control Hosp Epidemiol 1998; 19:494.
  51. Pegues DA, Han J, Gilmar C, et al. Impact of Ultraviolet Germicidal Irradiation for No-Touch Terminal Room Disinfection on Clostridium difficile Infection Incidence Among Hematology-Oncology Patients. Infect Control Hosp Epidemiol 2017; 38:39.
  52. Anderson DJ, Chen LF, Weber DJ, et al. Enhanced terminal room disinfection and acquisition and infection caused by multidrug-resistant organisms and Clostridium difficile (the Benefits of Enhanced Terminal Room Disinfection study): a cluster-randomised, multicentre, crossover study. Lancet 2017; 389:805.
  53. Rupp ME, Cavalieri RJ, Lyden E, et al. Effect of hospital-wide chlorhexidine patient bathing on healthcare-associated infections. Infect Control Hosp Epidemiol 2012; 33:1094.
  54. Noto MJ, Domenico HJ, Byrne DW, et al. Chlorhexidine bathing and health care-associated infections: a randomized clinical trial. JAMA 2015; 313:369.
  55. Longtin Y, Paquet-Bolduc B, Gilca R, et al. Effect of Detecting and Isolating Clostridium difficile Carriers at Hospital Admission on the Incidence of C difficile Infections: A Quasi-Experimental Controlled Study. JAMA Intern Med 2016; 176:796.
  56. Eyre DW, Cule ML, Wilson DJ, et al. Diverse sources of C. difficile infection identified on whole-genome sequencing. N Engl J Med 2013; 369:1195.
  57. Curry SR, Muto CA, Schlackman JL, et al. Use of multilocus variable number of tandem repeats analysis genotyping to determine the role of asymptomatic carriers in Clostridium difficile transmission. Clin Infect Dis 2013; 57:1094.
  58. Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother 2012; 67:742.
  59. Carling P, Fung T, Killion A, et al. Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years. Infect Control Hosp Epidemiol 2003; 24:699.
  60. McNulty C, Logan M, Donald IP, et al. Successful control of Clostridium difficile infection in an elderly care unit through use of a restrictive antibiotic policy. J Antimicrob Chemother 1997; 40:707.
  61. Johnson S, Samore MH, Farrow KA, et al. Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals. N Engl J Med 1999; 341:1645.
  62. Pear SM, Williamson TH, Bettin KM, et al. Decrease in nosocomial Clostridium difficile-associated diarrhea by restricting clindamycin use. Ann Intern Med 1994; 120:272.
  63. Lawes T, Lopez-Lozano JM, Nebot CA, et al. Effect of a national 4C antibiotic stewardship intervention on the clinical and molecular epidemiology of Clostridium difficile infections in a region of Scotland: a non-linear time-series analysis. Lancet Infect Dis 2017; 17:194.
  64. Dingle KE, Didelot X, Quan TP, et al. Effects of control interventions on Clostridium difficile infection in England: an observational study. Lancet Infect Dis 2017; 17:411.
  65. Wilcox MH, Shetty N, Fawley WN, et al. Changing epidemiology of Clostridium difficile infection following the introduction of a national ribotyping-based surveillance scheme in England. Clin Infect Dis 2012; 55:1056.
  66. Public Health England: Epidemiological Data--Clostridium difficile. http://www.hpa.org.uk/web/HPAweb&Page&HPAwebAutoListName/Page/1179745282388 (Accessed on February 28, 2014).
  67. Ashiru-Oredope D, Sharland M, Charani E, et al. Improving the quality of antibiotic prescribing in the NHS by developing a new Antimicrobial Stewardship Programme: Start Smart--Then Focus. J Antimicrob Chemother 2012; 67 Suppl 1:i51.
  68. Valiquette L, Cossette B, Garant MP, et al. Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associated disease caused by the hypervirulent NAP1/027 strain. Clin Infect Dis 2007; 45 Suppl 2:S112.
  69. Climo MW, Israel DS, Wong ES, et al. Hospital-wide restriction of clindamycin: effect on the incidence of Clostridium difficile-associated diarrhea and cost. Ann Intern Med 1998; 128:989.
  70. Biller P, Shank B, Lind L, et al. Moxifloxacin therapy as a risk factor for Clostridium difficile-associated disease during an outbreak: attempts to control a new epidemic strain. Infect Control Hosp Epidemiol 2007; 28:198.
  71. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353:2433.
  72. Labbé AC, Poirier L, Maccannell D, et al. Clostridium difficile infections in a Canadian tertiary care hospital before and during a regional epidemic associated with the BI/NAP1/027 strain. Antimicrob Agents Chemother 2008; 52:3180.
  73. Siegel JD, Rhinehart E, Jackson M, et al. Healthcare Infection Control Practices Advisory Committee 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings, June 2007 http://www.cdc.gov/ncidod/dhqp/gl_isolation.html (Accessed on August 10, 2007).
  74. Kallen AJ, Thompson A, Ristaino P, et al. Complete restriction of fluoroquinolone use to control an outbreak of Clostridium difficile infection at a community hospital. Infect Control Hosp Epidemiol 2009; 30:264.
  75. Settle CD, Wilcox MH, Fawley WN, et al. Prospective study of the risk of Clostridium difficile diarrhoea in elderly patients following treatment with cefotaxime or piperacillin-tazobactam. Aliment Pharmacol Ther 1998; 12:1217.
  76. Khan R, Cheesbrough J. Impact of changes in antibiotic policy on Clostridium difficile-associated diarrhoea (CDAD) over a five-year period in a district general hospital. J Hosp Infect 2003; 54:104.
  77. Nelson DE, Auerbach SB, Baltch AL, et al. Epidemic Clostridium difficile-associated diarrhea: role of second- and third-generation cephalosporins. Infect Control Hosp Epidemiol 1994; 15:88.
  78. American Academy of Pediatrics. Clostridium difficile. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.298.
  79. American Academy of Pediatrics. Children in out-of-home child care. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.132.