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Updated Clinical Practice Guidelines for CDI Show Improved Outcomes, but Adherence Issues Remain


Improved outcomes associated with fidaxomicin compared with vancomycin suggest benefits from its greater use in Medicare patients, although uptake remains low despite its recommended use.

The recently updated clinical practice guidelines on outpatient treatment for Clostridioides difficile infection (CDI) led to a decrease in metronidazole use and significant increases in fidaxomicin and vancomycin uptake, according to a recent analysis. But clinical outcomes did not improve, in part due to low fidaxomicin use.

Published in Open Forum Infectious Diseases, researchers examined outpatient CDI treatment utilization before and after the 2017 Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) CDI guideline update, which recommended treatment with fidaxomicin or vancomycin for CDI.

CDI is the most common health care–associated infection in adults and is associated with significant morbidity, mortality, and health care utilization and costs, especially in older patients. As evidence on CDI treatments accumulated, major changes in CDI treatment guidelines were introduced, noted the researchers, in which metronidazole was demoted from a first-line agent for nonsevere CDI.

“Vancomycin and fidaxomicin were recommended as first-line agents for initial or recurrent CDI episodes. The guidelines were recently updated in June 2021 with fidaxomicin as the sole recommended first-line agent and vancomycin as an alternative agent,” they added. “Despite these guideline changes, limited data exist on their impact on treatment utilization and clinical outcomes.”

A pre-post study design was conducted using Medicare data, with CDI treatment utilization and clinical outcomes (4- and 8-week sustained response, CDI recurrence) compared between patients indexed from April to September 2017 (preguideline period) and those indexed from April to September 2018 (postguideline period). Clinical outcomes associated with fidaxomicin were also compared with vancomycin using propensity score–matched analyses.

A total of 7389 and 7746 patients with an initial CDI episode in the pre- and postguideline periods, respectively, were included in the analysis. Both cohorts were primarily White and female. Approximately 40% of both cohorts were aged 66 to 74 years, and more than 50% of both cohorts had 5 or more Elixhauser comorbidities.

From the pre- to postguideline periods, metronidazole use decreased (initial CDI: 81.2% to 53.5%; recurrent CDI: 49.7% to 27.6%) while vancomycin (initial CDI: 17.9% to 44.9%; recurrent CDI: 48.1% to 66.4%) and fidaxomicin (initial CDI: 0.87% to 1.63%; recurrent CDI: 2.2% to 6.0%) use increased significantly (P < .001 for all).

Overall utilization of fidaxomicin remained low and most of the 27.7 percentage point decline in metronidazole shifted to vancomycin (P < .001). Clinical outcomes from the preguideline period to the postguideline period did not improve.

In propensity score–matched analyses, fidaxomicin vs vancomycin users had 4-week sustained response rates that were higher by 13.5% (95% CI, 4.0%-22.9%; P = .0058) and 30.0% (95% CI, 16.8%-44.3%; P = .0002) in initial and recurrent CDI cohorts, respectively. Recurrence rates were numerically lower for fidaxomicin in both cohorts.

Researchers concluded that findings regarding better outcomes associated with fidaxomicin in treating both initial and recurrent CDI suggest benefits from its greater use in the Medicare population and support the 2021 change in IDSA guidance recommending fidaxomicin over vancomycin.


Dubberke ER, Puckett JT, Obi EN, et al. Impact of updated clinical practice guidelines on outpatient treatment for Clostridioides difficile infection and associated clinical outcomes. Open Forum Infect Dis. 2022;9(10):ofac435. doi:10.1093/ofid/ofac435

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