By Richard R. Watkins, MD, MS, FACP, FIDSA
Synopsis: There is a lack of real-world data on using fidaxomicin for Clostridioides difficile infection (CDI). A retrospective, single-center study found that treatment of CDI with fidaxomicin leads to reduced clinical failure compared to oral vancomycin.
Source: Alsoubani M, Chow JK, Rodday AM, et al. The clinical effectiveness of fidaxomicin compared to vancomycin in the treatment of Clostridioides difficile infection, a single-center real-world experience. J Infect Dis. 2024;230:1501-1509.
Multiple randomized clinical trials (RCTs) have shown that treating Clostridioides difficile infection (CDI) with fidaxomicin leads to better outcomes compared to oral vancomycin. However, the populations and conditions present in RCTs often are not equivalent to those seen in clinical practice. There is a paucity of real-world data on using fidaxomicin for CDI, including outcomes based on ribotypes. Alsoubani and colleagues compared the rate of clinical failure between vancomycin and fidaxomicin for hospitalized patients with CDI.
The study included adult patients who were diagnosed with CDI between March 2011 and December 2021 hospitalized at a single academic medical center in Boston. Patients were excluded who had toxic megacolon, received a fecal microbiota transplant (FMT), or received treatment for more than 30 days. C. difficile isolates were ribotyped by polymerase chain reaction (PCR)-based fragment analysis.
The primary outcome of the study was a combined endpoint that included clinical failure, relapse within 30 days of finishing initial treatment, or dying from CDI. Secondary outcomes were the separate components of the combined endpoint, relapse at 90 days, and whether any relapse occurred after finishing therapy (i.e., total relapse). A secondary subgroup analysis based on the ribotype data was done to determine the relationship between ribotype and the combined clinical endpoint.
The study included 598 patients, 84 of whom received fidaxomicin. Most of the cases (90.8%) were primary infections. Fidaxomicin recipients were more likely to be older than those given vancomycin (68.2 years vs. 65.0 years; P = 0.043), to be male (63.1% vs. 49.0%; P = 0.018), and to have had previous CDI (7.1% vs. 1.8%; P < 0.05). Severe CDI occurred in 62% of cases based on white blood cell count (WBC) and/or creatinine criteria. One hundred sixty-eight patients (28.1%) were treated for more than 14 days, with 143 patients (27.8%) in the vancomycin group and 25 patients (29.8%) in the fidaxomicin group.
Regarding the clinical outcomes, the most frequent was relapse at 30 days (72 cases), then deaths attributed to CDI (32 cases), and clinical failure (15 cases). Relapse at 90 days occurred in 29 cases. The primary outcome occurred in eight (9.5%) patients who received fidaxomicin and 111 (21.6%) who received vancomycin. Of the 32 deaths associated with CDI, three (3.6%) occurred in the fidaxomicin group and 29 (5.6%) occurred in the vancomycin group. Adjusted multivariate analysis found fidaxomicin was associated with a 63% reduction in the risk of the primary outcome compared to vancomycin (hazard ratio [HR] = 0.37; 95% confidence interval [CI], 0.17-0.80). Patients with the primary outcome were more likely to spend time in the intensive care unit than those who did not (36.1% vs. 25.7%, respectively; P = 0.03). Furthermore, fidaxomicin was significantly associated with a reduced hazard of all the secondary outcomes.
Ribotyping was performed on 337 isolates. After controlling for ribotype 027, a hypervirulent strain, fidaxomicin lowered the primary outcome compared to vancomycin (HR = 0.19; 95% CI, 0.05-0.77). Fidaxomicin also reduced the risk of 30- and 90-day relapse. Compared to other ribotypes, those infected with 027 had an increased risk of 30-day relapse (HR = 3.5; 95% CI, 1.62-7.64) and total relapse (HR = 3.17; 95% CI, 1.57-6.40).
Commentary
Fidaxomicin was associated with a reduced risk of the combined endpoint (i.e., clinical failure, relapse within 30 days of finishing initial treatment, or dying from CDI) compared to vancomycin. These findings concur with data obtained during RCTs that led to the approval of fidaxomicin by the U.S. Food and Drug Administration (FDA) and other small clinical studies. Current clinical guidelines from the Infectious Diseases Society of America recommend fidaxomicin as first-line treatment for CDI.1
So why does vancomycin continue to be widely used despite being less effective than fidaxomicin? The answer likely is cost. A standard 10-day course of oral vancomycin is $41.51 on GoodRx while fidaxomicin is $4,779.89. Until the price of fidaxomicin becomes more reasonable, its use likely will remain limited.
The study had some limitations. First, because of the retrospective design, unmeasured confounding variables could have affected the results. Second, the study was conducted at a single academic institution in Boston, so the results might not be generalizable to other geographic areas or patient populations. Third, the number of patients who received fidaxomicin (n = 84) was small. This may have reduced the power to distinguish meaningful differences between the two drug groups. Fourth, there were some missing clinical and laboratory data that may have affected the results in uncertain ways. Finally, several results had wide confidence intervals, likely because of the relatively small sample size.
The results of the study support the notion that fidaxomicin should be used more frequently in clinical practice to treat CDI. Further effort should be made to find ways to reduce the drug’s high cost. If this occurs and fidaxomicin becomes more frequently prescribed, then it is likely that the morbidity and mortality associated with CDI will improve substantially.
Richard R. Watkins, MD, MS, FACP, FIDSA, is Professor of Medicine, Division of Infectious Diseases, Northeast Ohio Medical University, Rootstown, OH.
There is a lack of real-world data on using fidaxomicin for Clostridioides difficile infection (CDI). A retrospective, single-center study found that treatment of CDI with fidaxomicin leads to reduced clinical failure compared to oral vancomycin.
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