Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality

Abstract

Summary:We retrospectively evaluated 75 allogeneic stem cell transplant recipients to ascertain the incidence, risk factors and outcome of infection with Clostridium difficile. Ten patients (13%) had Clostridium difficile infection at a median of 38 days (range day −6 to day +72) following the transplant. There was no difference in the duration or severity of diarrhoea in patients with Clostridium difficile infection compared to the uninfected patients and no relationship to the prior antibiotic or chemotherapy usage, age, gender, underlying disease, donor type, CMV serostatus, total body irradiation or time to engraftment. The incidence of viral infections was increased in patients infected with Clostridium difficile (7/10 vs 15/65, P = 0.005, odds ratio 7.7), but the strongest association was with GVHD Ͼgrade 2 (5/10 vs 6/65 uninfected patients, P = 0.004, odds ratio 9.8). Patients infected with Clostridium difficile also suffered a higher non-relapse mortality with 7/10 patients succumbing to either GVHD or infections, compared to 19/65 patients in the uninfected group (P = 0.02, odds ratio 5.6). Thus Clostridium difficile infections in our study had a strong association with GVHD and increased non-relapse mortality. It is possible that Clostridium difficile toxin might predispose to increased severity of GVHD leading to an adverse outcome. Bone Marrow Transplantation (2000) 26, 871-876.

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

“…Unlike previous studies [10,11], we did not find any link between CDI and Grade I/II or Grade III/IV acute GVHD. This discrepancy in the association between the two clinical complications is not surprising since our study only addresses PT-CDI and very few patients developed acute GVHD prior to being discharged from the HPC transplant unit.…”

“…The incidence of CDI has increased greatly in the last decade, due to the epidemic strain of the pathogen, NAP1/BI/027 [14,15]. Although CDI has been studied in the setting of allogeneic HPC transplant [10,11], changes in the epidemiology of the disease in the last few years suggest the need for reevaluation CDI in this group of patients to determine if there has been any shift in the clinical characteristics. Furthermore, previous studies investigating CDI in this group of patients involved extended periods following HPC transplant, even though the risks for developing CDI vary with different time point after the transplant, being largely influenced by the white cell counts, temporal relationship to receiving the transplant preparative regimens, and the use of systemic antimicrobials.…”

“…Our findings led us to the question of the role of prophylactic CDI therapy in preventing PT-CDI. Since a previous study [10] found that the universal use of prophylactic metronidazole in all patients undergoing allogeneic HPC transplant did not reduce the incidence of post-transplant CDI, any use of prophylactic CDI therapy should, probably, only be carried out selectively for those with a recent history of CDI.…”

“…In addition, these patients are immunocompromised, receive extensive exposure to broad spectrum antimicrobials before and after HPC transplant, have compromise of the integrity of the intestinal mucosa due to the high dose chemoradiation given to the patients as part of transplant preparative regimens, and also often have very prolonged hospital stay [7][8][9]. Studies have shown the association of CDI with the development of acute Graft-versus-host disease (GVHD) [10,11] and increased non-relapse mortality [10] after allogeneic HPC transplant.…”

Rarity of toxigenic Clostridium difficile infections after hematopoietic stem cell transplantation: implications for symptomatic management of diarrhea

“…[2][3][4][5] However, none has focused specifically on C. difficile infections in the early post-transplant period, or symptomatic management. We sought to determine the incidence of CDT positivity at the time of initial diarrhea in autologous and allogeneic HSCT recipients.…”