Risk Factors and Outcome of C. difficile Infection after Hematopoietic Stem Cell Transplantation

Abstract

Patients who undergo hematopoietic stem cell transplants (HSCT) are at major risk of C. difficile (CD) infection (CDI), the most common cause of nosocomial diarrhea. We conducted a retrospective study, which enrolled 481 patients who underwent autologous (220) or allogeneic HSCT (261) in a 5-year period, with the aim of identifying the incidence, risk factors and outcome of CDI between the start of conditioning and 100 days after HSCT. The overall cumulative incidence of CDI based upon clinical evidence was 5.4% (95% CI, 3.7% to 7.8%), without any significant difference between the two types of procedures. The median time between HSCT and CDI diagnosis was 12 days. Out of 26 patients, 19 (73%) with clinical and symptomatic evidence of CDI were positive also for enzymatic or molecular detection of toxigenic CD; in particular, in 5 out of 26 patients (19%) CD binary toxin was also detected. CDI diagnoses significantly increased in the period 2018–2019, since the introduction in the microbiology lab unit of the two-step diagnostic test based on GDH immunoenzymatic detection and toxin B/binary toxin/027 ribotype detection by real-time PCR. Via multivariate analysis, abdominal surgery within 10 years before HSCT (p = 0.002), antibiotic therapy within two months before HSCT (p = 0.000), HCV infection (p = 0.023) and occurrence of bacterial or fungal infections up to 100 days after HSCT (p = 0.003) were significantly associated with a higher risk of CDI development. The 26 patients were treated with first-line vancomycin (24) or fidaxomicine (2) and only 2 patients needed a second-line treatment, due to the persistence of stool positivity. No significant relationship was identified between CDI and the development of acute graft versus host disease (GVHD) after allogeneic HSCT. At a median follow-up of 25 months (range 1–65), the cumulative incidence of transplant related mortality (TRM) was 16.6% (95% CI 11.7% to 22.4%) and the 3-year overall survival (OS) was 67.0% (95% CI 61.9% to 71.6%). The development of CDI had no significant impact on TRM and OS, which were significantly impaired in the multivariate analysis by gastrointestinal and urogenital comorbidities, severe GVHD, previous infections or hospitalization within two months before HSCT, active disease at transplant and occurrence of infections after HSCT. We conclude that 20% of all episodes of diarrhea occurring up to 100 days after HSCT were related to toxigenic CD infection. Patients with a history of previous abdominal surgery or HCV infection, or those who had received broad spectrum parenteral antibacterial therapy were at major risk for CDI development. CDIs were successfully treated with vancomycin or fidaxomicin after auto-HSCT as well as after allo-HSCT.

Path of least recurrence: A systematic review and meta‐analysis of fidaxomicin versus vancomycin for Clostridioides difficile infection

“…Of the remaining 22 full‐text articles reviewed, 14 studies (six RCTs and eight observational trials) met eligibility criteria for the final meta‐analysis (Figure 1). 9–12,20–30 Reasons for excluding full‐text articles included an unspecified follow‐up period for recurrence, missing data, population overlap, and concomitant use of fecal microbiota transplantation 31–37 . For included RCTs, three studies were assessed to have a low risk of bias and three with some concerns, primarily due to problems related to the unblinding of standard‐of‐care treatments (Figure 2A).…”

“…[9][10][11][12][20][21][22][23][24][25][26][27][28][29][30] Reasons for excluding full-text articles included an unspecified follow-up period for recurrence, missing data, population overlap, and concomitant use of fecal microbiota transplantation. [31][32][33][34][35][36][37] For included RCTs, three studies were assessed to have a low risk of bias and three with some concerns, primarily due to problems related to the unblinding of standard-of-care treatments (Figure 2A). For observational trials, only two studies, both reporting on outcomes associated with bezlotoxumab use, were not assessed to be of "good" quality (Figure 2B).…”

“…The sensitivity analysis for removal of individual studies found over 10% reductions in heterogeneity with the removal of the Guery study (the only RCT evaluating fidaxomicin extended-pulsed dosing and the Polivkova study). 9,24 While these studies had the lowest Reports excluded: Adjunctive fecal microbiota transplantation (n=2) 32,33 Population overlap (n=1) 31 Missing data (n=3) 34,35,37 Unclear follow-up period (n=1) 36 Studies included in review (n=14) [9][10][11][12][21][22][23][24][25][26][27][28][29][30] Controlled trials (n=6) Observational trials (n=8)…”

Prevalence of Clostridium difficile Infection in the Hematopoietic Transplantation Setting: Update of Systematic Review and Meta-Analysis

“…CDI has been increasingly discerned among HSCT recipients because of the fragility of the immune system, graft-versus-host disease (GVHD), and antibiotic usage or prophylaxis ( Ilett et al., 2019 ; Rosignoli et al., 2020 ; Jabr et al., 2021 ). Along with the growing cognition on CDI for clinical physicians and improving diagnostic capacity of laboratories on CDI, the relevant data on the prevalence of reported CDI have gradually increased in recent years.…”

Clostridioides difficile Infection in Patients after Organ Transplantation—A Narrative Overview

“…In another retrospective analysis, Rosignoli et al analyzed CDI incidence between the start of conditioning and 100 days after HSCT in a group of 481 patients who underwent autologous (220 patients) or allogeneic HSCT (261 patients). CDI incidence was 5.4%, without significant difference between the two types of HSCT [ 58 ]. Amberge et al, in a group of 727 patients with acute myeloid leukemia or myelodysplastic syndrome who underwent alloHCT, found CDI in 13% of cases and 14% of patients were identified as asymptomatic carriers of Clostridioides difficile .…”