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Risk Factors for Recurrent Clostridium Difficile Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients
Clostridium difficile infection (CDI) is one of the leading causes of hospital-acquired infections in recent times. Hematopoietic stem cell transplantation (HSCT) confers increased risk for CDI because of prolonged hospital stay, immunosuppression, the need to use broad spectrum antibiotics and a complex interplay of preparative regimen and graft versus host disease (GVHD)-induced gut mucosal damage. Although there have been studies describing the epidemiology and risk factors (RF) for CDI in HSCT recipients, there are little data regarding recurrence rate of CDI and RF associated with recurrence in this particular patient population, especially given the ubiquity of traditional RF for CDI in this population.
Aim:
To evaluate the recurrence rate and RF associated with recurrent CDI in allogeneic HSCT recipients.
Design and methods:
We conducted a retrospective, single center study of 499 allogeneic HSCT recipients transplanted between 2005 and 2012; of these, 61 (12%) developed CDI within 6 months prior to transplant or 2 years after transplant and were included in the analysis. Recurrent CDI was defined as recurrence after appropriate treatment of first episode which occurred in 20 (33%) of patients. Variables including age, antibiotic use, proton pump inhibitor use, presence of GVHD and other patient and transplant characteristics were analyzed as potential RFs for recurrence.
Results:
The 61 patients had a median age of 49 yrs (range 2-73 yrs) and M:F ratio of 1.1. 74% received myeloablative regimen and 26% received non-myeloablative regimen for HSCT and acute GVHD was seen in 59% of patients. Once-year incidence of CDI recurrence in our study was 31% compared to~20% recurrence in other series. Fine and Gray regression analysis identified the number of antecedent antibiotics other than those used to treat CDI as the only significant RF for recurrence (Hazard ratio (HR) 1.96, 95% Confidence Interval (CI) 1.09-3.52, P = 0.025). Most recurrences occurred within 6 months of first CDI (17/20, 85%) and recurrence of CDI was associated with a trend for increased risk of mortality (HR 2.36 [95% CI 0.98-5.71], P = 0.06).
Conclusion:
Use of antecedent antibiotics other than those used to treat CDI was associated with an increased risk of recurrent CDI in allogeneic HSCT recipients. CDI recurrence rate is high in the first 6 months following first episode of CDI and is associated with a trend for increased risk of mortality. This prompts the need for further investigation into secondary prophylaxis to prevent recurrent CDI.