Stem Cell Patients with C Difficile Benefit from Vancomycin, Fidaxomicin

An assessment of the frontline agents show similarities infection cure and recurrence rates at 30 days.

Adult patients with Clostrioides difficile (C difficile) infection who had received hematopoietic stem cell transplant (HSCT) benefitted similarly from frontline therapies fidaxomicin or oral vancomycin.

However, the new findings—presented at the Making A Difference in Infectious Disease (MAD-ID) 2021 Annual Meeting last week—would infer one provides significantly lower risk of treatment failure over the other in such adult patients.

Investigators from Atrium Health’s Carolinas Medical Center, led by Bliss Green, PharmD, sought to retrospectively evaluate clinical outcomes among patients with initial C difficile infection within 100 days after their stem cell transplant, treated with either fidaxomicin or oral vancomycin.

As observed in other MAD-ID 2021 research, the 2 agents provided similar outcomes in initial short and short-term mortality among adults with C difficile, but fidaxomicin provided a lower risk of infection recurrences at 1 month following treatment.

As Green and colleagues noted, hematopoietic stem cell transplant is generally associated with increased C difficile infection risk, without any specific treatment recommendations existing for the patient population.

“Fidaxomicin has been shown to have potential benefits over oral vancomycin, including decreased recurrence rates and the preservation of the intestinal microbiota,” they wrote, “however, there are limited data comparing therapies in HSCT recipients.”

Their single-center, retrospective cohort study of all adult transplant recipients diagnosed with initial C difficile infection episodes within 100 days of their procedure ran from March 11, 2014 to October 1, 2020. All observed patients had been treated with either agent.

C difficile infection diagnosis was based on the presence of at least 3 unformed stools within 24 hours, and/or physician-expressed concern for diarrhea, plus a positive test for infection on institutional protocol.

Patients with a history of C difficile infection, a prior infection within 90 days of HSCT, fulminant C difficile infection, or mortality prior to completion of initial treatment were excluded from the cohort.

Investigators sought a primary outcome of recurrence at 30 days from therapy completion, and secondary outcomes including C difficile infection recurrence at 60 and 90 days, as well as clinical cure of infection, sustained clinical response, treatment failure, acute graft versus host disease (aGVHD) occurrence, and vancomycin-resistant enterococci (VRE) infection occurrence within 90 days after completing therapy.

Their assessment included 61 patients from 159 screening; of them, 22 received fidaxomicin and 39 received vancomycin.

Green and colleagues observed no differences in 30-day infection recurrence among patients receiving fidaxomicin (0%) versus those receiving vancomycin (10.3%; P = .287). They similarly observed similarity in clinical cure (100% vs 92.3%, respectively; P = .547), as well as sustained clinical response at 30 days (100% vs 84.6%, respectively; P = .079).

GVHD occurrence (50% vs 45.5%, respectively; P >.99) and VRE infection (0% vs 2.6%, respectively; P >.99) were similar in the fidaxomicin and vancomycin treatment arms.

However, treatment failure incidence was more frequent in the oral vancomycin group (38.5%) than the fidaxomicin group (4.6%; P = .005), in which patient diarrhea persisted enough to require a change in therapy regimen. Median therapy duration was 14 days with oral vancomycin, versus 10 days with fidaxomicin (P <.001).

In their conclusion, investigators stressed the primary outcome similarities among the front-line agents in treating HSCT patients with C difficile infection.

“The rates of recurrence, clinical cure, and sustained clinical response in adult HSCT recipients with initial CDI treated with fidaxomicin or oral vancomycin were similar,” they wrote. “Fidaxomicin was associated with significantly lower rates of treatment failure compared to oral vancomycin.”