Epidemiology and outcomes of Clostridium difficile infections in hematopoietic stem cell transplant recipients

Abstract

Background. Clostridium difficile is the leading cause of infectious diarrhea among hospitalized patients and is a major concern for patients undergoing hematopoietic stem cell transplantation (HSCT). Risk factors and the natural history of C. difficile infection (CDI) are poorly understood in this population. Methods. We performed a retrospective nested case-control study to describe the epidemiology, timing, and risk factors for CDI among adult patients who received HSCTs at our center from January 2003 through December 2008. Results. The overall 1-year incidence of CDI was 9.2% among HSCTs performed (n = 999). The median time to diagnosis of CDI was short among both autologous and allogeneic HSCT recipients (6.5 days and 33 days, respectively). Risk factors for CDI in allogeneic HSCT recipients included receipt of chemotherapy prior to conditioning for HSCT, broad-spectrum antimicrobial use, and acute graft-versus-host disease (GVHD; adjusted odds ratio [AOR], 4.45; 95% confidence interval [CI], 1.54-12.84; P = .006). There was a strong relationship between early CDI and subsequent development of gastrointestinal tract GVHD in the year following allogeneic HSCT (P < .001). Gastrointestinal GVHD was also strongly associated with an increased risk for recurrent CDI (AOR, 4.23 [95% CI, 1.20-14.86]; P = .02). Conclusions. These results highlight the high incidence and early timing of CDI after HSCT. Early timing, coupled with the noted risk of pretransplant chemotherapy, suggests that the natural history of disease in some patients may involve colonization prior to HSCT. A potentially important interplay between CDI and GVHD involving the gastrointestinal tract was observed.

Figure 1.

One-year incidence of Clostridium difficile infection (CDI), stratified by transplant type. Overall CDI incidence did not vary significantly from 2003 through 2008. Infections were recorded from 7 days before transplant through 1 year after transplant. Patients having received >1 transplant were included once per calendar year.

Figure 2.

Timing of Clostridium difficile infection (CDI) by transplant type. Among autologous hematopoietic stem cell transplant (HSCT) recipients with CDI (n = 30), the median time to infection was 6.5 days compared with a median time to infection of 33 days among allogeneic HSCT recipients (n = 62). The inset demonstrates the timing of infection among allogeneic HSCT recipients. An additional 5 patients who received allogeneic transplants had disease after day 180 (not shown).

Figure 3.

Comparison of acute graft-versus-host disease (GVHD) following transplantation among allogeneic transplant recipients with and without Clostridium difficile infection (CDI; n = 180). The 1-year probability of developing grade 2 or higher gastrointestinal (GI) GVHD was 25% in case patients and 4.6% in control patients (log-rank test; P = .0001).