Research Article: A mathematical model of Clostridium difficile transmission in medical wards and a cost-effectiveness analysis comparing different strategies for laboratory diagnosis and patient isolation

Date Published: February 10, 2017

Publisher: Public Library of Science

Author(s): Vered Schechner, Yehuda Carmeli, Moshe Leshno, Gayatri Vedantam.


Clostridium difficile infection (CDI) is a common and potentially fatal healthcare-associated infection. Improving diagnostic tests and infection control measures may prevent transmission. We aimed to determine, in resource-limited settings, whether it is more effective and cost-effective to allocate resources to isolation or to diagnostics.

We constructed a mathematical model of CDI transmission based on hospital data (9 medical wards, 350 beds) between March 2010 and February 2013. The model consisted of three compartments: susceptible patients, asymptomatic carriers and CDI patients. We used our model results to perform a cost-effectiveness analysis, comparing four strategies that were different combinations of 2 test methods (the two-step test and uniform PCR) and 2 infection control measures (contact isolation in multiple-bed rooms or single-bed rooms/cohorting). For each strategy, we calculated the annual cost (of CDI diagnosis and isolation) for a decrease of 1 in the average daily number of CDI patients; the strategy of the two-step test and contact isolation in multiple-bed rooms was the reference strategy.

Our model showed that the average number of CDI patients increased exponentially as the transmission rate increased. Improving diagnosis by adopting uniform PCR assay reduced the average number of CDI cases per day per 350 beds from 9.4 to 8.5, while improving isolation by using single-bed rooms reduced the number to about 1; the latter was cost saving.

CDI can be decreased by better isolation and more sensitive laboratory methods. From the hospital perspective, improving isolation is more cost-effective than improving diagnostics.

Partial Text

Clostridium difficile infection (CDI) is a common and potentially fatal healthcare- associated infection; both the incidence and the severity have risen in recent years [1–2]. For CDI to develop, one has to acquire a toxigenic strain of C. difficile, which can either be carried asymptomatically or triggered to progress to disease [3]. The primary mode of C. difficile transmission within healthcare settings is from person-to-person via the fecal-oral route. It is commonly believed that C. difficile transmission is mainly from symptomatic patients with CDI and that transmission occurs when susceptible patients have direct or indirect (through the hands of healthcare workers) contact with fomites contaminated by the bacterium spores [4]. In addition, recent use of antimicrobials, which alter the normal gut flora, is a key trigger for symptomatic illness to develop [5]. Based on this understanding, the main components of CDI prevention in many practice guidelines include rapid and accurate diagnosis of CDI, contact isolation of symptomatic CDI cases, enhanced cleaning and disinfection of the environment and antibiotic stewardship programs [6–7]. However, molecular investigation of clinical isolates challenges this traditional view that most CDIs are acquired from known C. difficile infected patients and raises the possibility that at least in certain settings, transmission may largely result from asymptomatic (and therefore undiagnosed) carriers [8].

Managing CDI in healthcare settings is costly both in terms of diagnosis and isolation. In the short run, improving the sensitivity of testing has a paradoxically negative effect as the number of detected CDI cases increases. Yet, if we consider the total number of CDI cases (detected + undetected), the trend should be in the opposite direction since previously undetected cases are now detected and isolated, preventing further transmission. Indeed, in our hospital, if we account for cases missed because of imperfect test sensitivity, then the average daily number of CDI cases (detected + undetected) decreased by more than 1 (from 10.7 to 9.4 per 350 beds) due to the implementation of a more sensitive testing method. Therefore hospitals should not be discouraged by the seemingly ‘increasing numbers’ that accompany a change in diagnostic methods. In the long run, this will result in a reduction in the number of CDI cases as has been demonstrated [16].




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