Risk factors for recurrent Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients

Abstract

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 GvHD-induced gut mucosal damage. Our study evaluated risk factors (RF) for recurrent CDI in HSCT recipients given the ubiquity of traditional RF for CDI in this population. Of the 499 allogeneic HSCT recipients transplanted between 2005 and 2012, 61 (12%) developed CDI within 6 months before transplant or 2 years after transplant and were included in the analysis. Recurrent CDI occurred in 20 (33%) patients. One year incidence of CDI recurrence was 31%. Multivariable analyses identified the number of antecedent antibiotics other than those used to treat CDI as the only significant RF for recurrence (hazard ratio 1.96, 95% confidence interval 1.09-3.52, P = 0.025). Most recurrences occurred within 6 months of the first CDI, and the recurrence of CDI was associated with a trend for increased risk of mortality. This prompts the need for further investigation into secondary prophylaxis to prevent recurrent CDI. INTRODUCTIONClostridium difficile (C. diff) infection (CDI) is one of the leading causes of hospital-acquired infections in recent times. Allogeneic 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 chemo-preparative regimen and GvHD-induced gut mucosal damage. The incidence of CDI following autologous and allogeneic HSCT ranges from 5 to 20% 1-8 and recurrence rate has been~20%; 1 consistent with the general population. There are numerous studies describing the epidemiology and risk factors (RFs) of recurrent CDI in the general population, namely receipt of antibiotics, age 460 years, length of hospital stay and concomitant receipt of antacid medications. 9-12 Allogeneic HSCT recipients are a unique patient population, given the ubiquity of traditional risk factors and gut involvement with GvHD, with three studies showing an increased risk of CDI in patients with GvHD, 1,3,7 and there is a need to understand the risk of recurrence in this highly vulnerable group of immunosuppressed patients. Identifying these RFs will enable us to establish preventive measures for CDI by modifying our infection prevention and antibiotic utilization policies.

Incidence, course, and outcome of Clostridium difficile infection in children with hematological malignancies or undergoing hematopoietic stem cell transplantation

“…In PHO group, the incidence was 14% among all patients with malignancy. Higher rate of CDI in allogeneic HSCT recipients can occur due to a higher incidence of the main risk factors for CDI such as prolonged hospitalization, gastrointestinal mucosa damage due to chemotherapy, radiotherapy, frequent use of antibiotics, and development of gastrointestinal GVHD [ 26 ]. The type of malignancy can also influence a predisposition for CDI; however up to now, no clear relationship between the type of cancer and the risk of CDI has been described [ 27 ].…”

Recurrence ofClostridium difficileinfection in the Western Australian population

“…Recommendations for determining CDI classification suggest that an interval of 8 weeks or less after the onset of a previous episode (provided that symptoms from the index episode resolve with or without therapy) indicates recurrent CDI [13–16]. If the time elapsed between two episodes of CDI is >8 weeks, then the second episode is classed as a new infection as opposed to recurrence of the original infection.…”

Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients

“…The incidence of C. difficile infection (CDI) may be up to 9-fold higher in HSCT recipients than that of the general population [106], with most infections occurring early in the post-transplant period [105,107,108]. Risk factors for CDI in HSCT recipients include reception of chemotherapy prior to conditioning, exposure to high-risk antibiotics (e.g., fluoroquinolones and broad-spectrum β-lactam antibiotics) and mucositis [103,107,109,110]. The association between CDI and GVHD is complex; CDI is associated with gastrointestinal (GI) GVHD, which in turn predisposes to recurrent CDI [103,111].…”

“…No donor-derived infections were reported, with some studies performing extensive behavioral and microbiologic (serum, stool) screening of donors prior to FMT. [132,133] Findings such as these suggest that FMT may be considered for HSCT recipients in the future, especially in the setting of recurrent CDI where disease persistence, severity and relapse may be affected by factors such as continued immunosuppression and use of broad-spectrum antibiotics [110,133,135].…”