Incidence and Risk Factors Associated with Clostridium Difficile Infection in Cord Blood Transplant
Authors: Shah Mirat , Dickerson Bridget Ory , Savani Bipin N. , Thomas Lora , Chinratanalab Wichai , Engelhardt Brian , Goodman Stacey , Greer John P , Kassim Adetola A. , Sengsayadeth Salyka , Jagasia Madan 
Published: October 2019

Background: Clostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhea. The incidence of CDI in patients hospitalized for stem cell transplant (SCT) is much higher than in other inpatients, reaching between 12.5-30%. Antibiotic exposure, duration of hospitalization, and acute graft-versus-host disease (aGVHD) can contribute to the increased incidence of CDI. The incidence of CDI and risk factors associated with its development after cord blood transplant (CBT) have not been well-studied.

Methods: Ninety-five patients who received CBT at Vanderbilt University Medical Center from 2002 to 2013 were retrospectively reviewed. CDI was diagnosed using a stool toxin assay prior to 2011; DNA testing was used after 2011. CBT patients with CDI were compared to patients without CDI.

Results: Of 95 CBT patients, 34 (37.8%) developed CDI. Thirty day cumulative incidence of CDI was 37%. Comparative data on CDI incidence at our institution for general adult inpatients is being collected. Pre-transplant characteristics of patients are shown in Table 1 and transplant characteristics are shown in Table 2. There was no significant difference in incidence of aGVHD in patients with CDI (76.5%) and without CDI (59%). CDI was diagnosed in 41.6% (25/56) of patients with aGVHD who received systemic steroids and only in 23% (9/39) of patients with aGVHD who did not receive systemic steroids (P<0.05). Time (mean) to CDI (with death due to other causes as a competing risk) was shorter in patients receiving systemic steroids (80 days vs. 90 days, P<0.05). Among patients who received systemic steroids, CDI-infected patients had received higher dosages (mean 1.68 mg/kg vs. 1.28 mg/kg, P<0.05). There was no difference in incidence of CDI based on antibiotic exposure, type of antibiotic use, number of episodes of bacteremia, GI aGVHD, and recurrence of aGVHD (data not shown). Diagnostic modality (toxin assay vs. DNA testing) did not impact the CDI incidence rate. Using Cox-proportional hazards model, peak dose of steroids was an independent predictor of CDI (HR=2.42, 95% CI 1.02-4.01, p<0.05).

Conclusions: Our study shows that CDI is an important infectious complication of CBT with an incidence of 37%. CDI patients were more likely to have received systemic steroids for aGVHD, and at higher dosages. The connections between CDI, steroids, and aGVHD need to be explored further. Strategies to prevent CDI in this high-risk group need to be developed.

Table 1: Pre-transplant characteristics of patients with and without Clostridium difficile infection (CDI) CDI (N=34) No CDI (N=61) Age, y, mean (range) 21 (3 mo-57 y) 28 (6 mo-65 y) Gender, n (%) Female 19 (55.9) 29 (47.5) Male 15 (44.1) 32 (52.5) Race, n (%) African American 9 (26.5) 15 (24.6) Caucasian 20 (58.0) 37 (60.7) Hispanic 3 (8.8) 5 (8.2) Other 2 (5.9) 4 (6.5) Diagnosis, n (%) Acute leukemia 23 (67.6) 28 (45.8) Other leukemia 0 (0) 3 (4.9) Lymphoma 5 (14.7) 5 (8.2) Myeloid disorders 3 (8.8) 17 (27.9) Other 3 (8.8) 8 (13.1) Risk status, n (%) Low 7 (20.6) 19 (31.1) Intermediate 12 (35.3) 11 (18.0) High 12 (35.3) 27 (44.3)

Table 2: Transplant characteristics of patients with and without Clostridium difficile infection (CDI) CDI (N=34) No CDI (N=61) Type of transplant, n (%) Single unit 19 (55.9) 29 (47.5) Double unit 15 (44.1) 32 (52.5) Cell dose, mean, range 6.3 (0.7-27.3) 5.7 (1.7-16.1) Recipient CMV seropositive, n (%) 19 (55.9) 28 (45.9) Total body irradiation, n (%) 29 (85.3) 51 (83.6) Conditioning intensity, n (%) Ablative 24 (70.6) 40 (65.6) Non- ablative 10 (29.4) 21 (34.4) Use of ATG, n (%) 16 (47.1) 24 (39.3) GVHD prophylaxis, n (%) Mycophenolate mofetil 29 (85.3) 55 (90.2) Calcineurin inhibitors 34 (100) 61 (100) Duration of neutropenia, days, mean (range) 21.6 (7-37) 23 (9-49) Acute GVHD, n (%) 26 (76.5) 36 (59.0) Type of acute GVHD, n (%) Skin 13 (38.2) 24 (39.3) GI 19 (55.9) 23 (37.7) Liver 0 (0) 3 (4.9) Systemic steroids received for acute GVHD*, n (%) 25 (73.5) 31 (50.8) Steroid dose received for acute GVHD*, mean in mg/kg 1.68 1.28 Survival, n (%) Alive 16 (47.0) 34 (55.8) Deceased Disease 6 (17.6) 12 (19.7) Infection 9 (26.5) 11 (18.0) GVHD 2 (5.9) 1 (1.6) Other 1 (2.9) 3 (4.9)

*indicates statistical significance with p<0.05

Disclosures

No relevant conflicts of interest to declare.