CDI Following Liver Transplant Does Not Impact Mortality, Australian Study Finds

Clostridioides difficile infection (CDI) following liver transplant tends to be low-severity, and does not appear to affect survival rates, according to a new report from Australia.

The report also suggests that pre-transplant rifaximin (Xifaxan) may have a protective effect against post-transplant CDI, though that finding is preliminary and would need to be borne out in larger studies.

The findings were published in the journal Transplant Infectious Disease.

Corresponding author Avik Majumdar MBBS(Hons) MPHTM PhD FRACP, of the University of Sydney and the Royal Prince Albert Hospital, and colleagues, explained that CDI is a common hospital-associated infection both in Australia and other parts of the world. Patients receiving organ transplants are at a particularly high risk, the authors noted.

While previous studies have looked at the risk of CDI and CDI-related mortality among patients receiving liver transplants, Majumdar and colleagues noted that those studies have tended to be based in locations where hypervirulent strains of Clostridioides difficile are prevalent. Australia has largely avoided the hypervirulent strains, and so the investigators wanted to know whether and how CDI risk and outcomes might be different in their context.

The authors retrospectively examined the cases of 649 patients who underwent deceased-donor liver transplants between the years 2007 and 2017 at a single medical center. They then focused on the 32 patients (4.9%) who were diagnosed with CDI within a year after their transplant. The primary outcome of the study was overall survival, though Majumdar and colleagues also probed potential risk factors for CDI.

The data showed no statistical difference in patient survival between those liver transplant patients who were diagnosed with CDI and those who were not. After using a Cox Regression analysis, the authors found only one factor predicted mortality: age.

“We were expecting that C diff infection would be more prevalent in this group than what we found,” Majumdar told Contagion, “and similarly, we were surprised about the low numbers of recurrent and/or severe C diff infection.”

Majumdar said their rate of CDI (about 1 in 20) was higher than the CDI rate in the general population, though he said it was lower than most studies looking specifically at transplant recipients.

Majumdar and colleagues then used a multivariate logistic regression to see which factors might heighten or lessen the risk of CDI. They found patients who were given rifaximin prior to their transplant had a significantly lower risk of CDI (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.65 - 0.74 p=0.01) while antibiotic use in general increased risk significantly (OR 7.02, 95% CI 1.26 - 39.01, p=0.03). Length of hospital stay was also associated with an increased risk of CDI.

Majumdar said the rifaximin finding came as a surprise, though he cautioned that more research would be needed to confirm its apparent protective benefit.

Majumdar said there are a number of ways in which the setting of the study, in an area without hypervirulent strains, likely affected the results.

“We are fortunate in Australia in that we have only had isolated cases of hypervirulent C diff,” he said. “In fact, we had no cases in our centre at all over the study period (including in non-liver transplant recipients).”

He said earlier research has shown that CDI among liver transplant recipients in the US is as high as 16.7%, likely due to the presence of hypervirulent strains in North America. He added that prescribing practices are also likely different in America, a factor that could also impact the risk and severity of CDI in this patient group.