Clostridium difficile is a leading cause of infectious diarrhea in hematopoietic stem cell transplant (HSCT) recipients. Asymptomatic colonization of the gastrointestinal tract occurs before development of C. difficile infection (CDI). This prospective study examines the rates, risk factors, and outcomes of colonization with toxigenic and nontoxigenic strains of C. difficile in HSCT patients. This 18-month study was conducted in the HSCT unit at the Karmanos Cancer Center and Wayne State University in Detroit. Stool samples from the patients who consented for the study were taken at admission and weekly until discharge. Anaerobic culture for C. difficile and identification of toxigenic strains by PCR were performed on the stool samples. Demographic information and clinical and laboratory data were collected. Of the 150 patients included in the study, 29% were colonized with C. difficile at admission; 12% with a toxigenic strain and 17% with a nontoxigenic strain. Over a 90-day follow-up, 12 of 44 (26%) patients colonized with any C. difficile strain at admission developed CDI compared with 13 of 106 (12%) of patients not colonized (odds ratio [OR], 2.70; 95% confidence interval [95% CI], 1.11 to 6.48; P = .025). Eleven of 18 (61%) patients colonized with the toxigenic strain and 1 of 26 (4%) of those colonized with nontoxigenic strain developed CDI (OR, 39.30; 95% CI, 4.30 to 359.0; P < .001) at a median of 12 days. On univariate and multivariate analyses, none of the traditional factors associated with high risk for C. difficile colonization or CDI were found to be significant. Recurrent CDI occurred in 28% of cases. Asymptomatic colonization with C. difficile at admission was high in our HSCT population. Colonization with toxigenic C. difficile was predictive of CDI, whereas colonization with a nontoxigenic C. difficile appeared protective. These findings may have implications for infection control strategies and for novel approaches for the prevention and preemptive treatment of CDI in the HSCT patient population.

Clostridium difficile infection (CDI) is a major source of morbidity and mortality for hospitalized patients. Although most patients have a clinical response to existing antimicrobial therapies, recurrent infection develops in up to 30% of patients. Fecal microbiota transplant is a novel approach to this complex problem, with an efficacy rate of nearly 90% in the setting of multiple recurrent CDI. This review covers the current epidemiology of CDI (including toxigenic and nontoxigenic strains, risk factors for infection, and recurrent infection), methods of diagnosis, existing first-line therapies in CDI, the role of fecal microbiota transplant for multiple recurrent CDIs, and the potential use of fecal microbial transplant for patients with severe or refractory infection.

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Background Clostridium difficile (CD) is the leading cause of nosocomial diarrhea. After acquisition of CD, some patients (pts) remain colonized whereas others develop symptomatic CD infection (CDI). Hematopoietic stem cell transplant (HSCT) recipients are at higher risk of CDI than the general population. Rates of colonization and risk factors for CD colonization in the HSCT population are unknown. The goals of this study were to determine the rates and predictors of colonization with CD in HSCT pts at our institution. Methods We conducted a 16-month prospective study starting in December 2010 in the HSCT unit at the Karmanos Cancer Center. Pts who signed informed consent had stool samples collected within 72 hours of admission and weekly thereafter until discharge. Pts were followed up for 90 days after enrollment. Stool samples were cultured for CD and culture positive samples were tested by PCR for confirmation of toxigenic CD. Demographic information, risk factors and outcomes were examined. Results 154 patients who underwent allogeneic HSCT were enrolled in the study. Mean age for both CD colonized and non-colonized pts was 51 ±12.8 years, 59% were males. Overall, 47/154 (30%) pts were colonized with CD at admission; 23/154 (15%) with toxigenic CD. 8/23 (34%) pts colonized with toxigenic CD developed symptomatic CDI. Of the pts colonized with non-toxigenic CD, 7/24 (29%) acquired CD during the hospital stay. The median time to acquisition was week 2 of hospitalization. On bivariate analysis, underlying comorbid conditions and traditional risk factors for CDI like prior hospitalization, length-of-stay, antibiotic use, nasogastric tube and gastrointestinal tract procedures were found to be equally prevalent in both colonized and non-colonized population. The outcome in terms of graft versus host disease (GVHD) was also similar in both groups. The use of proton pump inhibitors was more prevalent in non-colonizers (56%) vs. colonizers (43%). However, it was not statistically significant (p=0.16). Similarly, lymphopenia seemed common amongst colonizers vs. non-colonizers (67% vs. 58%) but was not statistically significant (p=0.2). Conclusion Colonization with toxigenic CD is high in our HSCT recipients at hospital admission. Symptomatic CDI occurs in a third of pts colonized with toxigenic CD. Unlike in the general population, traditional risk factors for CD colonization are not predictive of colonization in our allogeneic HSCT pts. Novel approaches such as active surveillance to detect colonized patients to guide infection control measures and to direct “pre-emptive” therapy should be evaluated in this population. Disclosures: No relevant conflicts of interest to declare.

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