Peri‐transplant clostridium difficile infections in patients undergoing allogeneic hematopoietic progenitor cell transplant

Abstract

Clostridium difficile infections (CDI) remain the leading cause of infectious diarrhea among hospitalized patients in this country. Patients with hematologic malignancies, especially those who undergo hematopoietic progenitor cell transplants are particularly at risk for developing CDI. One hundred and forty seven consecutive allogeneic hematopoietic progenitor cell transplants were analyzed for peri-transplant Clostridium difficile infections (PT-CDI). Sixteen patients (11%) developed PT-CDI (Median time 5 7 days after transplant). The probability for developing PT-CDI during the peri-transplant period was 12.3%. History of CDI was strongly associated with the development of PT-CDI (P 5 0.008) (OR 5 5.48) (P 5 0.017). These patients also developed PT-CDI much earlier than in those without a history (median 1 day vs. 8 days, P 5 0.03). The probability for developing PT-CDI for those with a history was 39%. There was a trend toward significance (P 5 0.065) between matched related donor grafts and the development of PT-CDI (OR 5 0.245) (P 5 0.08). Age, sex, diagnosis, transplant preparative regimens, Graft-versus-host disease (GVHD) prophylaxis, grade 3/4 acute GVHD, or use of antimicrobials within 8 weeks of transplant were not associated with PT-CDI. Non-CDI-related deaths occurred in one patient in the PT-CDI group and nine in the group without PT-CDI. In the remaining 139 patients, the length of hospital stay for those with PT-CDI was significantly longer than those without (mean 27 days vs. 22 days; P 5 0.02).

Changes in intestinal microbiota and their effects on allogeneic stem cell transplantation

“…CDI in patients who underwent allogeneic HSCT was not associated with any increased risk of mortality . There are several reported risk factors for the incidence of CDI following allogeneic HSCT, including carbapenem use, previous C difficile colonization, CDI within nine months before allogeneic HSCT, total body irradiation, cord blood transplant, and onset of acute GVHD up to one year after allogeneic HSCT .…”

“…A discussion of the effects of a disrupted intestinal microbiome on the development of GVHD following allogeneic HSCT is not complete without including C difficile infection (CDI) since both diseases are related to intestinal dysbiosis and the presence of one affects the development of the other. CDI is one of the most commonly observed complications following allogeneic HSCT, estimated to occur in 10% to 15% of patients . With the emergence of the more virulent NAP‐1/027 strain, the incidence of CDI is expected to increase rapidly.…”

Intestinal dysbiosis and allogeneic hematopoietic progenitor cell transplantation

“…A study by Jain et al found that 12 percent of patients admitted to their institution for SCT were colonized with toxigenic C. difficile [14]. Agha et al reported that 11 percent of SCT recipients developed peri-transplant CDI [15]. Interestingly, the only factor independently associated with development of CDI was a previous history of the same.…”

“…Interestingly, the only factor independently associated with development of CDI was a previous history of the same. Patients with matched-related grafts had a lower likelihood of developing CDI in the study population [15]. A review by Alonso et al found an overall CDI rate of 9.2% among SCT recipients, with higher rates among allogeneic transplant recipients compared to those who underwent autologous transplant (12.5 vs. 6.5%) [11, 12].…”

“…The eradication of endogenous flora by preparative chemotherapeutic regimens opens a larger microbiological space than exposure to standard antimicrobials, leaving a wider available niche in these patients. The discovery that matched-related hematopoietic grafts were associated with a lower risk of CDI than matched-unrelated grafts suggests that pre-existing microbiome characteristics play a role in determining CDI susceptibility [15]. Pairing donors and recipients with similar gut microbiota, and probable similar past environmental exposures, may produce less disruption to endogenous flora after transplant.…”