Impact of Clostridioides difficile infection and its treatment on allo-HSCT outcomes

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are more susceptible to Clostridioides difficile infection (CDI). Antibiotics used to treat CDI can lead to the development or worsening of graft-versus-host disease (GvHD) or gastrointestinal-GvHD (GI-GvHD).¹ The relationship between CDI and GvHD remains unclear as well as the impact of CDI and its treatment on allo-HSCT outcomes.¹

Here, we summarize a multicenter, real-world study by Piekarska et al.¹ published in Scientific Reports evaluating the impact of CDI and the type of CDI treatment on the occurrence of GvHD in patients undergoing allo-HSCT.

Study design¹

• This was a multicenter study assessing retrospective and prospective data from patients attending Polish Adult Leukemia Group transplant centers.
• Eligible patients received allo-HSCT and had confirmed CDI.
• For first-line treatment of non-severe/severe CDI, patients in the prospective group received vancomycin.
  • For severe/sudden onset of CDI, patients received combination therapy of vancomycin and metronidazole.

Key findings¹

• In total, 109 patients were included in this study.
• CDI was diagnosed at a median of 11 days posttransplant.
  • In total, 58.7% of patients developed CDI within 100 days posttransplant.
• Colonization with multidrug-resistant bacteria before CDI diagnosis occurred in 65.1% of patients.
• There was an increased incidence of aGvHD in patients after they developed CDI (Figure 1).

aGvHD, acute graft-versus-host disease; CDI, Clostridioides difficile infection; GI-GvHD, gastrointestinal-GvHD.
*Data from Piekarska, et al.^1
†Chronic GvHD: 5.3%.
^‡Chronic GI-GvHD: 2.1%.

 

• Treatment failure of CDI was higher with metronidazole compared with vancomycin (38.2% vs 6.2%, respectively; p < 0.001).
• Patients who received combination therapy had an increased rate of GvHD and GI-GvHD compared to those who received:
  • metronidazole monotherapy: p = 0.01 and p = 0.007, respectively, or
  • vancomycin monotherapy: p = 0.003 and p < 0.001, respectively.
• Patients treated with metronidazole monotherapy or as a part of a combination therapy showed a higher incidence of GI-GvHD vs those treated with vancomycin (p = 0.03).
• Second-line treatment of CDI was more frequently needed in the metronidazole group, which was also associated with an increased rate of GI-GvHD (p < 0.001).
  • Changing to second-line treatment was associated with increased mortality due to GvHD at 6-month follow-up (p = 0.001).
  • Increased mortality was also associated with the presence of GvHD before CDI (p < 0.005) or the development/worsening of GvHD after CDI (p < 0.05).
• In the multivariate analysis, the predictors of death included:
  • the occurrence of aGvHD before CDI (hazard ratio [HR], 3.19; 95% confidence interval [Cl], 1.65–6.16; p = 0.009); and
  • the need to change to second-line treatment of CDI (hazard ratio, 4.83; 95% CI, 2.46-9.47; p < 0.001).

Key learnings
Incidence of GvHD and GI-GvHD increased in patients with CDI who were treated with metronidazole (as a monotherapy or in combination therapy) compared with those treated with vancomycin. In patients diagnosed with CDI after allo-HSCT, highly efficacious therapies (such as vancomycin and fidaxomicin) should be administered as first-line treatment to limit the occurrence of GvHD.