Role of asymptomatic Clostridium difficile carriers in intra-hospital transmission and healthcare-associated Clostridium difficile infection: a transmission modeling analysis

Background: Asymptomatic C. difficile carriers outnumber symptomatic cases in hospitals but most infection control targets symptomatic cases. A recent study where asymptomatic patients admitted to a 354-bed hospital were tested for C. difficile carriage and isolated if positive found a large decline in healthcare-associated C. difficile infections (HA CDI, Longtin et al. JAMA Intern Med 2016). However, they were unable to collect data on antibiotic use among known carriers and it is unclear whether the drop in HA CDI was due to a) reduced transmission when isolated carriers progressed to disease due to no delay in isolation, b) less antibiotic use among known carriers, and/or c) lower transmission due to isolation of infectious carriers. Our aim was to identify the roles of these mechanisms in reducing HA CDI during the intervention.

Methods: We developed a compartmental transmission model of the natural history of C. difficile, CDI testing, total antibiotic use and isolation practices in the 354-bed hospital. Using parameter values derived from the published literature, we fitted the model to a time series of hospital-wide CDI using maximum likelihood for 5 scenarios (Table). We compared results using likelihood ratio tests to find which mechanisms most likely explained the intervention’s success.

Results: Compared to routine practices, we found a significant combined effect of carriage testing and isolation and reduction of transmission from isolated carriers (Scenario 4, p = 0.02). Adding antibiotic stewardship among isolated carriers did not significantly improve the fit (Scenario 5, p > 0.3). Other combinations were not significant.

Conclusion: The reduction in HA CDI following the intervention was largely due to isolation of carriers. Further studies should assess the transmission risk from carriers and cases as well as investigate how antibiotic stewardship measures among known C. difficile carriers can reduce their risk of progression to CDI.

Table: Combinations of mechanisms studied to explain impact of Clostridium difficile intervention

Scenario	Carriage testing and isolation	Antibiotic stewardship among isolated carriers	Reduction of transmission from isolated carriers
1 (Reference)	No	No	No
2	Yes	No	No
3	Yes	Yes	No
4	Yes	No	Yes
5	Yes	Yes	Yes