Real-World Data Suggest Fidaxomicin Reduces Clostridioides difficile Reinfection Versus Vancomycin

Fidaxomicin and vancomycin are both recommended treatments for Clostridioides difficile infection (CDI), with fidaxomicin as a possible frontrunner in reducing CDI recurrence based on randomized, controlled clinical trials. However, a recent study published in Antibiotics questioned which drug is most effective at preventing recurrence in real-world clinical settings versus strictly in controlled trial environments.

In a meta-analysis of 4 randomized, controlled clinical trials of fidaxomicin conducted by the Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America guidelines panel, fidaxomicin was shown to elicit better rates of sustained clinical response without recurrence. When the European Society of Clinical Microbiology and Infectious Diseases excluded an open-label trial that was used in the IDSA meta-analysis, fidaxomicin and vancomycin had comparable initial response rates, but fidaxomicin significantly reduced recurrence at 28 days after initial treatment.

However, considering guidelines from the American College of Gastroenterology, which highlight results from a propensity-matched national cohort from the Veterans Affairs (VA), the applicability of those clinical trial findings is being questioned. The VA data showed recurrence rates of 24.4% with either drug at 90 days after initial CDI index date and treatment with similar rates of death in patients given either medication (23% vs. 22% for fidaxomicin and vancomycin, respectively).

“The findings from the national VA cohort create uncertainty regarding whether the improvements in recurrence observed in randomized, controlled trials can be replicated in standard medical practice outside of a randomized, controlled trial,” study authors wrote. “A national multi-center evaluation of fidaxomicin’s impact on CDI recurrence outside of the VA system has not been conducted to our knowledge.”

A total of 15,674 patients who were admitted to the hospital, diagnosed with C diff infection, and treated with vancomycin or fidaxomicin were eligible for the study, which used data from the Cerner Health Facts Database and included de-identified information on 69 million patients at 750 facilities. A total of 889 patients were given fidaxomicin and 14,785 vancomycin. Study authors matched the 889 patients who received fidaxomicin to the same number of those given vancomycin.

The unadjusted 90-day recurrence rate based on hospital readmission was 8.3% with fidaxomicin and 12.3% in patients given vancomycin (P < 0.001). Univariable results showed that a few factors were associated with recurrence, which 12% of patients overall experienced. Male sex, race, census region, treatment at rural facilities, severe CDI, and previous antibiotic use were among these risk factors.

Overall, the risk of CDI recurrence was significantly lower with fidaxomicin treatment, which is consistent with findings from the meta-analysis conducted by the European Society of Clinical Microbiology and Infectious Diseases. Study authors note that one reason these findings may differ from those in the VA cohort could be severity of CDI cases—while the VS cohort only evaluated severe cases, the current study also included non-severe cases. The current cohort also showed lower rates of recurrence overall than the others, possibly due to the study’s definition of recurrence, which required rehospitalization for recurrent CDI within 90 days of the end of initial inpatient therapy.

“Our findings provide additional data regarding the real-world effectiveness of fidaxomicin that should encourage clinicians, hospitals, and third-party payors to utilize fidaxomicin as the preferred antimicrobial treatment option for CDI,” the authors concluded. “The significant reduction in CDI recurrence observed in randomized controlled trials has now been replicated in a national sample utilizing real-world data.”

The study was limited in its retrospective nature and because it relies on data only from facilities that participate in Cerner Health Facts. Even so, the findings suggest that fidaxomicin may be the best option for first-line CDI treatment.

“Since fidaxomicin is better than vancomycin for an index case of CDI, we recommend despite the limitations of this study that fidaxomicin might be a better treatment, but confirmatory studies are needed,” the authors wrote.

Reference

Hall RG 2nd, Cole TJ, Shaw C, Alvarez CA. The risk of Clostridioides difficile recurrence after initial treatment with vancomycin or fidaxomicin utilizing Cerner Health Facts. Antibiotics (Basel). Published online February 23, 2022. doi:10.3390/antibiotics11030295