- Top of page
- Materials and Methods
- Supporting Information
Clostridium difficile colitis (CDC) is the leading cause of nosocomial infectious diarrhoea and is associated with substantial morbidity and mortality. The past decade has witnessed a rise in the incidence and severity of CDC in hospitals across North America and Europe, largely attributable to the emergence of highly virulent strain of this organism.[1, 2]
Patients with ulcerative colitis (UC) are at increased risk of acquiring CDC.[3-5] The incidence of CDC among UC patients has also been rising in recent years, with CDC now being implicated in up to 5% of UC hospital admissions.[3-5] Nationwide studies have further reported that CDC is associated with a 3.8–5.5-fold higher acute mortality risk among hospitalised UC patients.[3, 6] The impact of CDC on acute colectomy risk in UC patients has been less consistent across studies.[3, 6-8]
In addition to increasing short-term health risks, CDC may pose sustained health risks to UC patients. Chronic C. difficile colonisation following an acute infectious episode may increase the risk of future CDC episodes in many patients. Moreover, the impact of CDC on UC disease behaviour remains unknown. One study reported that CDC was associated with a greater 1-year colectomy risk in these patients. However, no study has assessed the longer term impact of CDC on health outcomes in this population. As UC afflicts more than 500 000 individuals across North America, this could have significant implications for hospital care policy and health resource utilisation in these patients.[10, 11] Therefore, we sought to investigate the impact of CDC on 5-year health outcomes among hospitalised UC patients.
- Top of page
- Materials and Methods
- Supporting Information
In this study of hospitalised UC patients, CDC was an independent risk factor for both 5-year mortality and 5-year rehospitalisation. CDC was also strongly predictive of in-hospital death and longer acute care LOHS, although the former association could not be adjusted for covariates. Conversely, CDC was not independently associated with 5-year or in-hospital risks of colectomy or 5-year risk of UC-specific hospital readmission. Colectomy risk was mainly influenced by disease-specific and hospital-specific factors in this study, which is compatible with other studies demonstrating that UC severity and colonic disease extent are predictive of colectomy risk in UC patients.[16-19]
Collectively, these findings implicate an episode of CDC as a potential risk factor for long-term mortality and rehospitalisation among hospitalised UC patients, possibly as a result of recurrent CDC episodes or through altering long-term UC behaviour. Colonised C. difficile spores and vegetative organisms in some patients could theoretically give rise to abnormal and/or exaggerated immune responses, as has been hypothesised for other host and pathogenic microbes in IBD.[20-26] In addition, the physiologic stress associated with CDC may exacerbate other illnesses, such as cardiovascular disease and renal insufficiency, which could further influence long-term prognosis in these patients.
Clostridium difficile colitis may also give rise to a more aggressive form of acute colitis, which may partly explain the higher in-hospital mortality risk observed in these patients. Use of immunosuppressive therapy, in addition to antibiotics, to treat CDC in the setting of UC may have also increased the duration and/or severity of colitis in many individuals. In addition, some physicians may be inclined to persist longer with medical therapy in C. difficile-infected patients, which could lead to serious complications in patients who are not responding to therapy. It is possible that some patients who died would have benefited from colectomy earlier in the course of their acute illness. CDC could also have exacerbated life-threatening co-morbidities in some patients.
On the other hand, it is possible that unadjusted differences in co-morbidity burden, baseline UC severity or immunosuppressive medication use between infected and uninfected patients influenced the observed associations in this study. Although the Charlson index has been widely validated as a predictor of mortality among hospitalised patients, it may not capture the full extent of co-morbidity burden among hospitalised UC patients.[13, 28-30] Baseline disease severity was adjusted through variables that had reasonable face validity, including prior hospitalisation for UC and UC duration (based on the notion that UC is most aggressive in the first 2 years following diagnosis[31, 32]), as a validated UC disease activity index could not be calculated. Still, admission of some patients with less severe colitis to expedite surgery may have partly selected for patients who were less likely to suffer death, but certain to undergo colectomy among uninfected patients. In addition, no information was available regarding in-hospital medications in this study. Additional studies with more complete adjustment for confounding are thus required to confirm the findings of this study.
Furthermore, C. difficile exposure status may have been misclassified in a proportion of patients, as a result of both misreporting on hospital discharge abstracts as well as inadequate stool testing for C. difficile. No studies have evaluated the diagnostic accuracy of CDC among UC patients within hospital administrative databases. Exposure misclassification may have largely been a random event, which would have attenuated measured associations without invalidating significant ones. However, some patients with fulminant colitis on presentation may have died or undergone colectomy prior to C. difficile testing, which could have further biased the measured associations low. Conversely, C. difficile testing may have been performed more often in patients with severe or treatment-refractory disease, which could have then biased the measured associations high. Future studies with more rigorous case ascertainment methods are thus required to corroborate the findings of this study. Importantly, a high level of coding accuracy has been demonstrated for demographic data and codes for procedures in the Ontario version of the CIHI-DAD.
This is the first study to demonstrate an association between CDC and long-term mortality risk among hospitalised UC patients. Population-based studies have reported a 3.8–5.5-fold higher in-hospital mortality risk and a significantly longer acute care LOHS with CDC in this setting.[3, 6] Although longer LOHS may be a risk factor for C. difficile acquisition, studies have shown that this infection is predominantly acquired prior to hospital admission among IBD patients.[4, 5] With respect to colectomy risk, a US nationwide study reported a decreased risk, a UK nationwide study demonstrated a 1.7-fold higher risk, and two single centre studies reported no difference in risk of in-hospital colectomy with CDC among hospitalised UC patients, although the latter studies may have been underpowered.[7, 8] Notably, one study reported a 2.4-fold higher colectomy risk at 1 year with CDC in this setting. In addition to differences in study methodology, varying strategies for hospital-based care of UC patients in different settings may account for some of these differences.
In summary, this study has demonstrated that CDC is associated with an increased risk of short-term and long-term adverse outcomes, particularly mortality, among hospitalised UC patients. Future prospective studies with rigorous case ascertainment methods and confounder adjustment, which evaluate the impact of CDC among both hospitalised and ambulatory IBD patients, will be important to confirm and expand upon the findings of this study. In particular, aetiologic factors underlying the observed associations in this study require elucidation. Importantly, the results of this study should not be generalised to ambulatory UC patients, who carry a variety of different C. difficile strains as compared with nosocomial patients and who may thus face considerably different risks with this infection. Efforts should nevertheless be made by all health care practitioners to reduce the risk of C. difficile transmission among UC patients.