Early <i>Clostridium difficile</i> Infection during Allogeneic Hematopoietic Stem Cell Transplantation

<div><p><i>Clostridium difficile</i> infection (CDI) is frequently diagnosed in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We characterized early-transplant CDI and its associations, and analyzed serially-collected feces to determine intestinal carriage of toxigenic <i>C. difficile</i>. Fecal specimens were collected longitudinally from 94 patients during allo-HSCT hospitalization, from the start of pre-transplant conditioning until up to 35 days after stem cell infusion. Presence of <i>C. difficile</i> 16S rRNA and <i>tcdB</i> genes was determined. Clinical variables and specimen data were analyzed for association with development of CDI. Historical data from an additional 1144 allo-HSCT patients was also used. Fecal specimens from 37 patients (39%) were found to harbor <i>C. difficile</i>. Early-transplant CDI was diagnosed in 16 of 94 (17%) patients undergoing allo-HSCT; cases were generally mild and resembled non-CDI diarrhea associated with transplant conditioning. CDI was associated with preceding colonization with tcdB-positive <i>C. difficile</i> and conditioning regimen intensity. We found no associations between early-transplant CDI and graft-versus-host disease or CDI later in transplant. CDI occurs with high frequency during the early phase of allo-HSCT, where recipients are pre-colonized with toxigenic C. difficile. During this time, CDI incidence peaks during pre-transplant conditioning, and is correlated to intensity of the treatment. In this unique setting, high rates of CDI may be explained by prior colonization and chemotherapy; however, cases were generally mild and resembled non-infectious diarrhea due to conditioning, raising concerns of misdiagnosis. Further study of this unique population with more discriminating CDI diagnostic tests are warranted.</p>