Mathematical Models of Pre- and Post-Intestinal Microbiota Restoration for the Prevention of C. difficile Infections

Healthcare-associated Clostridium difficile infection (CDI) is a major source of hospital-acquired infections, in some settings eclipsing infections by methicillin-resistant Staphylococcus aureus. Two of the risk factors for these infections are the use of antibiotics and proton pump inhibitors, both of which disrupt the natural intestinal flora, allowing C. difficile to proliferate. The use of probiotics to help combat this disruption, and fecal microbiota transplantation (FMT) to restore healthy intestinal flora have both been suggested as potential interventions to help control CDI within hospitals. The evidence base for evaluating these interventions is underdeveloped however, especially when considering them as routine hospital policy.

Using parameters obtained from the literature and surveillance data, we use a stochastic compartmental model to simulate the use of both probiotics and FMT to prevent recurrent and incident CDI within a 12-bed intensive care unit. Patients were treated under a number of different scenarios, altering the proportion treated, the efficacy of microbiota restoration, as well as whether they are treated post-infection to prevent recurrence, or prophylactically to reduce the risk of incident infection.

The model suggests that the use of post-infection FMT is an effective means of reducing recurrent cases of CDI, while it has no effect on incident infections. The efficacy of prophylactic intestinal flora restoration, using either FMT or probiotics is dependent on the frequency of administration, and the duration of efficacy. We discuss what levels of efficacy are needed for sustained decreases in incident infections, and whether or not current estimates from observational studies approach this threshold.