Epidemiology, Risk Factors, and Outcomes After Early Posttransplant Clostridiodes difficile Infection in Renal Transplant Recipients

Abstract

Background: Modifiable risk-factors associated with Clostridioides difficile infection (CDI) in renal-transplant (RTX) have not been clearly established and peri-transplant risk has not been described. Objective: Evaluate epidemiology, risk-factors and outcomes after CDI occurring in the first 90 days after RTX (CDI-90).Methods: Observational cohort study/survival analysis of adult RTX recipients from 1/1/2012-12/31/2015. Primary outcome was CDI-90 incidence/risk-factors. Secondary outcome was evaluation of post-90 day transplant outcomes. Results: 982 patients met inclusion criteria; 46 with CDI-90 and 936 without (comparator). CDI incidence in the total population was 4.7% at 90 days, 6.3% at 1 year, and 6.4% at 3 years. Incidence of CDI-90 was 5%; time to diagnosis was 19.4±25 days (median 7). Risk-factors for CDI-90 were alemtuzumab induction (Hazard ratio [HR] 1.5, 95% CI(1.1-2.0), p = 0.005) and age at transplant (HR 1.007/year, 95% CI (1.002-1.012), p= 0.007). However, risk-factors for CDI at any time were different; donation-after-circulatory-death (DCD) donor (HR 2.5 95% CI (1.3-4.9), p = 0.008) and female gender (HR 1.6 95% CI (1.0-2.7), p = 0.049). On Kaplan-Meier, CDI-90 appeared to have an impact on patient/graft survival, however when analyzed in a multivariable stepwise Cox proportional hazards model, only age was significantly associated with survival ( p = 0.002). Conclusion and Relevance: Incidence of CDI-90 is low, mostly occurring in the first post-operative month. Risk-factors vary temporally based on time from transplant. In the early post-op period induction agent and age at transplant are significant, but not after. Associations between CDI and negative graft outcomes appear to be largely driven by age. Future studies validating these risk-factors as well as targeted prophylaxis strategies and their effect on long term graft outcomes and the host microbiome are needed.

A Systematic Literature Review on Risk Factors for and Timing of Clostridioides difficile Infection in the United States

“…Other studies were of case-control/case-cohort (n = 26), prospective cohort (n = 7), or nested case-control design (n = 2). For one study, it was not clear if the design was retrospective or prospective [28]. No articles were included from manual searches of the reference lists of metaanalyses or systematic reviews.…”

“…However, in specific patient populations, age was often not related to CDI risk. For example, age was a significant risk factor in only two of four studies in patients receiving solid organ transplants [28,[39][40][41], one of three studies in patients with bowel disease [42][43][44], and one of four studies in patients with cancer [45][46][47][48].…”

“…Twenty-six articles included a risk estimate for sex (Fig. 2); a significantly higher risk of CDI in women compared with men was reported in 12 studies [28,43,[47][48][49][50][51][52][53][54][55]. This ranged from an aOR of 1.02 (95% CI 1.00-1.04; p value not presented) in a mixed study population in a large database study [34] to an aOR of 6.3 (95% CI 1.7-24.0; p \ 0.01) in patients with urinary tract infections (UTIs) [50].…”

“…In patients receiving stem cell transplant, the median time for CDI occurrence was generally in the first 2 or 3 weeks after transplantation [94,105,[133][134][135][136]. In patients receiving organ transplantation, time to CDI varied but was often more than 3 weeks after transplantation [28,41,66]. In patients undergoing surgery, the mean or median times of CDI diagnoses were almost all within 3 weeks of the surgical procedure [61,72,76,98,137].…”