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A Mathematical Model to Evaluate the Routine Use of Fecal Microbiota Transplantation to Prevent Incident and Recurrent Clostridium difficile Infection

  • Eric T. Lofgren (a1), Rebekah W. Moehring (a2), Deverick J. Anderson (a2), David J. Weber (a1) (a3) and Nina H. Fefferman (a4)...

Fecal microbiota transplantation (FMT) has been suggested as a new treatment to manage Clostridium difficile infection (CDI). With use of a mathematical model of C. difficile within an intensive care unit (ICU), we examined the potential impact of routine FMT.

Design, Setting, and Patients.

A mathematical model of C. difficile transmission, supplemented with prospective cohort, surveillance, and billing data from hospitals in the southeastern United States.


Cohort, surveillance, and billing data as well as data from the literature were used to construct a compartmental model of CDI within an ICU. Patients were defined as being in 1 of 6 potential health states: uncolonized and at low risk; uncolonized and at high risk; colonized and at low risk; colonized and at high risk; having CDI; or treated with FMT.


The use of FMT to treat patients after CDI was associated with a statistically significant reduction in recurrence but not with a reduction in incident cases. Treatment after administration of high-risk medications, such as antibiotics, did not result in a decrease in recurrence but did result in a statistically significant difference in incident cases across treatment groups, although whether this difference was clinically relevant was questionable.


Our study is a novel mathematical model that examines the effect of FMT on the prevention of recurrent and incident CDI. The routine use of FMT represents a promising approach to reduce complex recurrent cases, but a reduction in CDI incidence will require the use of other methods to prevent transmission.

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1.Cohen SH, Gerding DN, Johnson S, et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010;31(5):431455.
2.Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol 2012; 107(7):10111019.
3.Garey KW, Sethi S, Yadav Y, DuPont HL. Meta-analysis to assess risk factors for recurrent Clostridium difficile infection. J Hosp Infect 2008;70(4):298304.
4. Agency for Healthcare Research and Quality. HCUPnet. 2006. Accessed September 17, 2012.
5.Miller BA, Chen LF, Sexton DJ, Anderson DJ. Comparison of the burdens of hospital-onset, healthcare facility-associated Clostridium difficile infection and of healthcare-associated infection due to methicillin-resistant Staphylococcus aureus in community hospitals. Infect Control Hosp Epidemiol 2011;32(4):387390.
6.van Nood E, Vrieze A, Nieuwdorp M, et al.Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368(5):407415.
7.You DM, Franzos MA, Holman RRSuccessful treatment of fulminant Clostridium difficile infection with fecal bacterio-therapy. Ann Intern Med 2008;148(8):632633.
8.Petrof EO, Gloor GB, Vanner SJ, Weese SJ. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: “RePOOPulating” the gut. Microbiome 2013;1(3).
9.Guidance for industry: enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat Clostridium difficile infection not responsive to standard therapies. US Food and Drug Administration. Federal Register 2013;78(138):4296542966.
10.Anderson DJ, Miller BA, Chen LF, et al.The network approach for prevention of healthcare-associated infections: long-term effect of participation in the Duke Infection Control Outreach Network. Infect Control Hosp Epidemiol 2011;32(4):315322.
11.McDonald LC, Coignard B, Dubberke E, et al.Recommendations for surveillance of Clostridium difficile-associated disease. Infect Control Hosp Epidemiol 2007;28(2):140145.
12.Weber D, Rutala W, Miller M, Huslage K. Role of hospital surfaces in the transmission of emerging health care-associated pathogens: norovirus, Clostridium difficile, and Acinetobacter species. Am J Infect Control 2010;38(5suppl 1):S25S33.
13.Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 2009;7(7):526536.
14.Owens RC, Donskey CJ, Gaynes RP, Loo VG, Muto CA. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis 2008;46(suppl 1):S19S31.
15.Moehring RW, Lofgren ET,Anderson DJ. Impact of change to molecular testing for Clostridium difficile infection on healthcare facility-associated incidence rates. Infect Control Hosp Epidemol 2013;34(10):10551061.
16.Kane RL, Shamliyan TA, Mueller C, Duval S, Wilt TJ. The association of registered nurse staffing levels and patient outcomes: systematic review and meta-analysis. Med Care 2007;45(12): 11951204.
17.Ward NS, Read R, Afessa B, Kahn JM. Perceived effects of attending physician workload in academic medical intensive care units: a national survey of training program directors. Crit Care Med 2012;40(2):400405.
18.Thompson DR, Hamilton DK, Cadenhead CD, et al.Guidelines for intensive care unit design. Crit Care Med 2012;40(5):15861600.
19.Gillespie DT. Exact stochastic simulation of coupled chemical reactions. J Phys Chem 1977;81(25):23402361.
20.Chen LF, Carriker C, Staheli R, et al.Observing and improving hand hygiene compliance: implementation and refinement of an electronic-assisted direct-observer hand hygiene audit program. Infect Control Hosp Epidemiol 2013;34(2):207210.
21.Oughton MT, Loo VG, Dendukuri N, Fenn S, Libman MD. 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(10):939944.
22.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(6):565570.
23.Ballermann MA, Shaw NT, Mayes DC, Gibney RTN, Westbrook JI. Validation of the Work Observation Method By Activity Timing (WOMBAT) method of conducting time-motion observations in critical care settings: an observational study. BMC Med Inform Oeds Mak 2011;11:32.
24.Riggs MM, Sethi AK, Zabarsky TF, Eckstein EC, Jump RLP, Donskey CJ. 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(8):992998.
25.Guerrero DM, Nerandzic MM, Jury LA, Jinno S, Chang S, Dons-key CJ. Acquisition of spores on gloved hands after contact with the skin of patients with Clostridium difficile infection and with environmental surfaces in their rooms. Am J Infect Control 2012; 40(6):556558.
26.Bobulsky GS, Al-Nassir WN, Riggs MM, Sethi AK, Donskey CJ. Clostridium difficile skin contamination in patients with C. difficile-associated disease. Clin Infect Dis 2008;46(3):447450.
27.Sethi AK, Al-Nassir WN, Nerandzic MM, Bobulsky GS, Donskey CJ. Persistence of skin contamination and environmental shedding of Clostridium difficile during and after treatment of C. difficile infection. Infect Control Hosp Epidemiol 2010;31(1):2127.
28.Lanzas C, Dubberke ER, Lu Z, Reske KA, Grohn YT. Epidemiological model for Clostridium difficile transmission in healthcare settings. Infect Control Hosp Epidemiol 2011;32(6):553561.
29.Pépin J, Saheb N, Coulombe MA. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis 2005;41(9):12541260.
30.Mandeli LA, Wunderink RG, Anzueto A, et al.Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44(Suppl. 2):S27S72.
31.Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, Stamm WE. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Clin Infect Dis 1999;29(4):745758.
32.Giordano P, Weber K, Gesin G, Kubert J. Skin and skin structure infections: treatment with newer generation fluoroquinolones. Ther Clin Risk Manag 2007;3(2):309317.
33.Vanderhoff BT, Tahboub RM. Proton pump inhibitors: an update. Am Fam Physician 2002;66(2):273280.
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Infection Control & Hospital Epidemiology
  • ISSN: 0899-823X
  • EISSN: 1559-6834
  • URL: /core/journals/infection-control-and-hospital-epidemiology
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