Increased risk of Clostridium difficile infection and diarrhea in asymptomatically colonized patients

Background:

Previous studies suggest that patients who are asymptomatically colonized with Clostridium difficile (CD) are at decreased risk for subsequent diarrhea and clinical Clostridium difficile infection (CDI). Asymptomatic colonization is common among patients admitted to tertiary care hospitals. A study at our large tertiary care hospital showed an at-admission prevalence of asymptomatic colonization of 9.4%.

Objective:

To determine the risk of subsequent clinically diagnosed CDI and diarrhea among a cohort of patients found to be asymptomatically colonized with CD.

Methods:

We included patients who had previously participated in a study of at-admission asymptomatic CD colonization assessment at St. Mary's Hospital, Mayo Clinic, Rochester MN in March – April, 2009. Colonization was assessed by testing stool for presence of toxigenic CD by real-time PCR that detects tcdC. CD colonization status was not reported to patients or their physicians. All patients who had provided stool samples were included in this follow up evaluation. Follow up after hospital dismissal was performed using a combination of telephone call and chart review between 3 and 4 months following determination of CD colonization status. Data collected included diagnosis of CDI, diarrhea, and antibiotic use any time following determination of initial colonization status.

Results:

A total of 320 patients had previously been assessed for asymptomatic CD colonization. After excluding 12 patients with previous CDI, 308 patients were included in the follow-up evaluation. Of these, 29 were CD colonized and 279 were non-colonized. Follow up was obtained for 271/308 subjects (88%, 25 (86%) colonized and 254 (89%) non-colonized patients). Clinically diagnosed CDI was found to develop in 4/25 (16%) of CD-colonized and 4/247 (2%) of non-colonized patients during the follow up period. Using multivariable logistic regression, after controlling for age and antibiotic use, the risk of CDI was significantly higher in those with previous asymptomatic CD colonization compared to  non-colonized patients (odds ratio 10.1 (95% CI 2.3 – 44.2)). Diarrhea developed in 7/25 (28%) of CD-colonized and 25/247 (10%) of non-colonized patients. Using multivariable logistic regression analysis, after controlling for age and antibiotic use, the risk of subsequent diarrhea during the follow up period in CD-colonized patients was also significantly greater than in non-colonized patients (odds ratio 3.3 (95% CI 1.3 – 8.9)).

Conclusions:

This study suggests that hospitalized patients who are asymptomatically colonized with toxigenic CD may be at higher risk for development of clinically significant CDI and diarrhea, compared with non-colonized patients. This finding is contrary to previous reports and should be explored further.