Healthcare-associated Clostridium difficile infection (HA CDI)

Risk of symptomatic infection and duration of disease

Clostridium difficile infection (CDI) is defined by a positive laboratory test for C. difficile (C. difficile toxin A and/or/B or positive culture for toxin-producing C. difficile or cell cytotoxicity assay or PCR) or pseudomembranous colitis, identified through colonoscopy or histopathology or autopsy (ECDC, 2012).

We performed a search for systematic reviews and two additional searches for primary articles on the outcomes ‘length of hospital stay’ (LOS), ‘death’ and ‘sepsis’. To differentiate between health states (i.e. mild and moderate vs. severe CDI), data on the severity of CDI were collected in a non-systematic fashion.

For the outcomes ‘LOS’, ‘death’ and ‘sepsis’ we extracted risk differences, whereas for the outcomes ‘recurrence’ and ‘post-colectomy state’ absolute risks were used. In the case of the outcome ‘post-colectomy state’ this approach was chosen assuming that colectomy is a rare event in patients without CDI.

The outcome tree was constructed starting from acute CDI that was divided into two different health states: mild and moderate versus severe CDI, the latter representing 1.5–15% of CDI episodes (HPSC, 2012; Kanerva, 2013; Bauer, 2011; CDAD KISS, 2012). The duration of the acute disease was described by the attributable LOS, a surrogate marker for short-term complications such as ICU stay or toxic megacolon. The attributable LOS ranged from zero to eight days (Campbell, 2013; Dodek, 2013; Kyne, 2002; Song, 2008; Tabak, 2013; Vonberg, 2008). The transitional probability for the outcome ‘death’ was expressed by the overall attributable mortality (including death after colectomy) of 0–11% (lower boundary of -3% was set to zero) (Dodek, 2013; Song, 2008; Tabak, 2013; Oake, 2010).

It was not possible to make a quantitative analysis of the transitional probabilities for the outcomes ‘death’ and ‘LOS’ by pooling the data. This was due to (a) differing methods of adjustment by design or analysis (matching, propensity score matching, multivariate analysis) across the studies, (b) adjustment factors not being comparable between the studies and (c) variance estimates not being provided for all studies.

The study by Pépin et al (2005), conducted during an epidemic caused by C. difficile PCR ribotype 027 reported the highest estimates for LOS and attributable mortality. As the study setting was not representative of a setting where CDIs generally occur, after consultation with the experts we decided not to include the study.

The transitional probabilities for the outcome ‘post-colectomy state’ ranged between 0.2 and 3.8% (Bhangu, 2012). The duration of this outcome was lifelong.

Calculation of a point estimate by pooling incidences did not seem appropriate without knowing the baseline risks for colectomy within the studies. In the majority of articles, the characteristics of the study population only referred to patients with colectomy because the selected studies focused on outcomes after colectomy.

Since the systematic search for sepsis did not reveal any eligible studies, this outcome was omitted.

From a clinical point of view, recurrence is a major issue in patients with CDI. Nevertheless, inclusion of recurrence (e.g. by introducing one or more loops in the outcome tree) may have led to double counting of cases, and subsequently to an overestimation of the burden of disease, depending on how the issue of recurrence was dealt with by the prevalence data fitted into the tree. Therefore, we chose not to include recurrence in the outcome tree.

Model input summary

Table 1. Transition probabilities used in the outcome tree

 Health outcome
 (Health state)

Distribution of health states in health outcome

Transition probability

Source/assumption

Symptomatic disease

Uncomplicated

Complicated

 

85-98.5%

1.5-15%

 

HPSC, 2012; Kanerva, 2013; Bauer, 2011; CDAD KISS, 2012

Fatal cases following symptomatic infection

 

0-11%

Dodek, 2013; Song, 2008; Tabak, 2013; Oake, 2010

Post-colectomy state

 

0.2-3.8%

Bhangu, 2012

Table 2. Disability weights and duration

Health outcome
(Health state)

Disability Weight (DW) (Haagsma, 2015)

Duration

DW

Label

In years

Source/assumption

Symptomatic disease

Uncomplicated

 

Complicated

 

0.073-0.149

 

0.239 (0.202-0.285)

 

Diarrhoea, from mild to moderate

Diarrhoea, severe

0-0.0219

Campbell, 2013; Dodek, 2013; Kyne, 2002; Song, 2008; Tabak, 2013; Vonberg, 2008

Post-colectomy state

0.125 (0.104-0.155)

Stoma

Remaining Life Expectancy

 

References

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BAUER, M. P., NOTERMANS, D. W., VAN BENTHEM, B. H., BRAZIER, J. S., WILCOX, M. H., RUPNIK, M., MONNET, D. L., VAN DISSEL, J. T., KUIJPER, E. J. & GROUP, E. S. 2011. Clostridium difficile infection in Europe: a hospital-based survey. Lancet, 377, 63-73.

CAMPBELL, R., DEAN, B., NATHANSON, B., HAIDAR, T., STRAUSS, M., THOMAS, S., CAMPBELL, R., DEAN, B., NATHANSON, B., HAIDAR, T., STRAUSS, M. & THOMAS, S. 2013. Length of stay and hospital costs among high-risk patients with hospital-origin Clostridium difficile-associated diarrhea. Journal of medical economics, 16, 440-448.

CDAD. 2012. CDAD KISS reference data 2012. Available: http://www.nrz-hygiene.de/surveillance/kiss/cdad-kiss/.

DODEK, P. M., NORENA, M., AYAS, N. T., ROMNEY, M. & WONG, H. 2013. Length of stay and mortality due to Clostridium difficile infection acquired in the intensive care unit. Journal of critical care, 28, 335-40.

Haagsma JA, Maertens de Noordhout C, Polinder S, Vos T, Havelaar AH, Cassini A, Devleesschauwer B, Kretzschmar ME, Speybroeck N, Salomon JA. Assessing disability weights based on the responses of 30,660 people from four European countries. Population Health Metrics 2015; 13: 10

HEALTH PROTECTION SURVEILLANCE CENTRE (HPSC), A. R. 2012. Health Protection Surveillance Centre (HPSC), Annual Report 2012. Available: http://www.hpsc.ie/A-Z/Gastroenteric/Clostridiumdifficile/CdifficileSurveillance/AnnualReports/File,14557,en.pdf

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TABAK, Y. P., ZILBERBERG, M. D., JOHANNES, R. S., SUN, X., MCDONALD, L. C., TABAK, Y. P., ZILBERBERG, M. D., JOHANNES, R. S., SUN, X. & MCDONALD, L. C. 2013. Attributable burden of hospital-onset Clostridium difficile infection: A propensity score matching study. Infection Control and Hospital Epidemiology, 34, 588-596.

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