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. 2014 Jan;35(1):18-27.
doi: 10.1086/674394. Epub 2013 Dec 2.

A mathematical model to evaluate the routine use of fecal microbiota transplantation to prevent incident and recurrent Clostridium difficile infection

Eric T Lofgren  1 , Rebekah W Moehring, Deverick J Anderson, David J Weber, Nina H Fefferman
Affiliations

A mathematical model to evaluate the routine use of fecal microbiota transplantation to prevent incident and recurrent Clostridium difficile infection

Eric T Lofgren et al. Infect Control Hosp Epidemiol. 2014 Jan.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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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Conflict of interest statement

Potential conflicts of interest. E.T.L. has received research grant support from Merck. D.J.A. participates on the speaker’s bureau of and has received research grant support from Merck. All other authors report no conflicts of interest relevant to this article. All authors submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and the conflicts that the editors consider relevant to this article are disclosed here.

Figures

FIGURE 1
FIGURE 1
Schematic representation of the compartmental flow of a mathematical model of the use of fecal microbiota transplantation (FMT) to prevent incident and recurrent Clostridium difficile infection (CDI). Inset indicates the potential routes of bacterial contamination between patients and healthcare workers, whereas gray arrows indicate the movements within the model influenced by the simulated intervention. Healthcare personnel are classified as uncontaminated (US) or contaminated (H), and patients are classified into low risk and uncolonized (Up), low risk and colonized (CP), high risk and uncolonized (UA), high risk and colonized (CA), patients with CDI (D), and patients undergoing FMT (CT).
FIGURE 2
FIGURE 2
A single stochastic realization of a mathematical model of the use of fecal microbiota transplantation to prevent incident and recurrent Clostridium difficile infection (CDI). The top panel shows the level of hand contamination in healthcare workers over a 24-hour period, whereas the bottom 2 panels depict the number of patients and their current health state over a 1-year period.
FIGURE 3
FIGURE 3
Simulated recurrent and incident cases of Clostridium difficile infection (CDI) for 6 levels of fecal microbiota transplantation after CDI to prevent the development of recurrence. All simulation outcomes are shown, with the results summarized with box-and-whisker plots depicting the median, 25th and 75th percentiles, and 1.5 times the interquartile range.
FIGURE 4
FIGURE 4
Simulated recurrent and incident cases of Clostridium difficile infection (CDI) for 6 levels of fecal microbiota transplantation after receipt of high-risk medication to prevent the development of infection and recurrence among patients who received antibiotics or proton pump inhibitors. All simulation outcomes are shown, with the results summarized with box-and-whisker plots depicting the median, 25th and 75th percentiles, and 1.5 times the interquartile range.
FIGURE 5
FIGURE 5
Simulated recurrent and incident cases of Clostridium difficile infection (CDI) for 6 levels of combined fecal microbiota transplantation (FMT) after receipt of high-risk medication to prevent the development of infection and recurrence among patients who received antibiotics or proton pump inhibitors and FMT after CDI to prevent the development of recurrence. All simulation outcomes are shown, with the results summarized with box-and-whisker plots depicting the median, 25th and 75th percentiles, and 1.5 times the interquartile range.
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Comment in

  • Fecal microbiota therapy: ready for prime time?
    Rao K, Young VB, Aronoff DM. Rao K, et al. Infect Control Hosp Epidemiol. 2014 Jan;35(1):28-30. doi: 10.1086/674395. Epub 2013 Dec 2. Infect Control Hosp Epidemiol. 2014. PMID: 24334795 Free PMC article. No abstract available.

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