Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of <i>Clostridioides difficile</i> Infection in Adults

Johnson, Stuart; Lavergne, Valéry; Skinner, Andrew M; Gonzales-Luna, Anne J; Garey, Kevin W.; Kelly, Ciarán P.; Wilcox, Mark H.

doi:10.1093/cid/ciab549

Cited by 359 publications

(386 citation statements)

References 35 publications

Supporting

Mentioning

286

Contrasting

Unclassified

Order By: Relevance

“…In recent years, however, guidelines, such as those published by the IDSA and SHEA, have recommended initial fidaxomicin (preferred) or vancomycin (alternative) over metronidazole for the treatment of non-severe CDI. 5 Our findings support the recommendation to use vancomycin when fidaxomicin is unavailable, which is applicable to institutions that rely on metronidazole and vancomycin for the treatment of CDI. A strength of our investigation was the long duration of follow-up, 26 weeks in a pragmatic real-world setting, which allowed for conclusions about the impact of initial vancomycin treatment on new incident infection, defined as a CDI episode occurring >8 weeks after the initial infection.…”

Section: Discussionsupporting

confidence: 80%

“…In recent years, however, there has been a shift to initial vancomycin to treat first-episode non-severe CDI at our institution, which is consistent with guidelines published by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA), when fidaxomicin is unavailable. 5 Importantly, guidelines published by the European Society of Clinical Microbiology and Infectious Diseases, the World Society of Emergency Surgery, and the Australasian Society of Infectious Diseases still recommend the use of metronidazole for the first episode of non-severe disease. [6][7][8] Although initial fidaxomicin or vancomycin treatment is recommended by most major guidelines to treat severe CDI, there exists a discrepancy in treatment recommendations for firstepisode non-severe CDI.…”

mentioning

confidence: 99%

“…[6][7][8] Although initial fidaxomicin or vancomycin treatment is recommended by most major guidelines to treat severe CDI, there exists a discrepancy in treatment recommendations for firstepisode non-severe CDI. [5][6][7][8] Few studies have been conducted with long-term follow-up evaluating the use of initial vancomycin compared to initial metronidazole to treat non-severe inpatient CDI. In 2 large randomized controlled trials with follow-up of 3 weeks and 4 weeks, respectively, subgroup analyses stratified by severity did not demonstrate significant differences in relapse rates between the vancomycin and metronidazole treatment groups for nonsevere CDI.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Initial vancomycin versus metronidazole for the treatment of first-episode non-severe Clostridioides difficile infection

Zhang

Beckett

Abouanaser

et al. 2021

ASHE

View full text Add to dashboard Cite

Objective: Clostridioides difficile infection (CDI) is the leading cause of infectious nosocomial diarrhea. Although initial fidaxomicin or vancomycin treatment is recommended by most major guidelines to treat severe CDI, there exists varied recommendations for first-episode non-severe CDI. Given the discrepancy in current treatment guidelines, we sought to evaluate the use of initial vancomycin versus metronidazole for first-episode non-severe CDI. Methods: We conducted a retrospective cohort study of all adult inpatients with first-episode CDI at our institution from January 2013 to May 2018. The initial vancomycin versus initial metronidazole cohorts were examined using a multivariate logistic regression model. Results: The study cohort of 737 patients had a median age of 72.3 years, and 357 of these patients (48.4%) had hospital-acquired infection. Among 326 patients with non-severe CDI, recurrence, new incident infection, and 30-day mortality rates were 16.2%, 10.9%, and 5.3%, respectively, when treated with initial metronidazole, compared to 20.0%, 1.4%, and 10.0%, respectively, when treated with initial vancomycin. In an adjusted multivariable analysis, the use of initial vancomycin for the treatment of non-severe CDI was associated with a reduction in new incident infection (adjusted odds ratio [ORadj], 0.11; 95% confidence interval [CI], 0.02–0.86; P = .035), compared to initial metronidazole. Conclusions: Initial vancomycin was associated with a reduced rate of new incident infection in the treatment of adult inpatients with first-episode non-severe CDI. These findings support the use of initial vancomycin for all inpatients with CDI, when fidaxomicin is unavailable.

show abstract

Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Initial vancomycin versus metronidazole for the treatment of first-episode non-severe Clostridioides difficile infection

Zhang

Beckett

Abouanaser

et al. 2021

ASHE

View full text Add to dashboard Cite

show abstract

“…To estimate the comparative efficacy of fidaxomicin vs. vancomycin we conducted a metaanalysis of the three double blind, placebo-controlled, randomized controlled trials identified by IDSA-SHEA 8 wherein fidaxomicin was compared head-to-head with vancomycin [3][4][5] . We excluded a fourth trial which was open label and compared a longer total duration of fidaxomicin (30-days vs. 10-days in all other included studies) 9 .…”

Section: Methodsmentioning

confidence: 99%

Fidaxomicin as first line: What will it cost in the USA and Canada?

Patel

Senécal

Spellberg

et al. 2021

Preprint

View full text Add to dashboard Cite

ImportanceRecent changes in the Infectious Diseases and Healthcare Epidemiology Societies of America (IDSA-SHEA) guidelines for managing Clostridioides difficile infections (CDI) have placed fidaxomicin as first-line treatment for CDI.ObjectiveTo estimate the net cost of first line fidaxomicin as compared to vancomycin in the American and Canadian healthcare systems and to estimate the price points at which fidaxomicin would become cost saving.Data sourcesWe identified all randomized controlled trials comparing fidaxomicin with vancomycin through the 2021 IDSA-SHEA guideline update. Medication costs were obtained from wholesale prices (US) and the Quebec drug formulary (Canada). The average cost of a CDI recurrence was established through two systematic reviews using PubMed.Study selectionFor fidaxomicin efficacy, we included double-blind and placebo-controlled trials. For the systematic review of recurrence costs, studies were included if they were primary research articles, had a cost-analysis of CDI, included cases of recurrent CDI, and were calculated with cost parameters from American or Canadian healthcare systems. Studies were excluded if the population was solely pediatric or hospitalized.Data extraction and SynthesisFor the efficacy meta-analysis, data was pooled using a random effects model. For the costs review, literature screening was performed by 2 independent reviewers. The mean cost across identified studies was adjusted to 2021 dollars.Main Outcomes and MeasuresThe primary outcome of the meta-analysis was CDI recurrence at day 40. The primary outcome of the systematic review was the average cost of a CDI recurrence in the American and Canadian healthcare systems. The objective was to estimate the net cost per recurrence prevented and the price point below which fidaxomicin would be cost saving.ResultsAt current drug pricing, the estimated additional cost of a 10-day course of fidaxomicin compared to vancomycin in order to prevent one recurrence was $46,178USD (95%CI $36,942-$69,267) and $13,760CAD (95%CI $11,008-$20,640), respectively. The estimated mean systemic cost of a CDI recurrence was $14,506USD and $8,588CAD, respectively. When priced below $1550USD and $800CAD, fidaxomicin was likely to become cost saving.Conclusions and RelevanceThe increased drug expenditure on fidaxomicin will not be offset through recurrence prevention unless fidaxomicin price is re-negotiated.Key PointsQuestionAt what price point does new guideline recommendations for changing from vancomycin to fidaxomicin for first line C. difficile infection (CDI) therapy become cost saving?FindingsFor a 10-day course, we estimated that compared to vancomycin, treatment with fidaxomicin costs an additional $46,178USD to prevent one CDI recurrence and that treating one recurrence costs $14,506USD. The current cost of fidaxomicin is only partially offset through prevention of recurrences. Upfront therapy with fidaxomicin would be cost saving if the price were reduced below $1550USD per treatment.MeaningNew guideline updates could add billions in additional drug costs for CDI treatment.

show abstract

“…Additional benefits of fidaxomicin include a narrower spectrum of activity, less frequent dosing, and rarity of resistance [ 33 ]. IDSA 2021 updated guidelines specifically address the use of fidaxomicin in adults, now recommending its use for both the first episode of C. difficile , and now also in recurrent episodes over vancomycin [ 34 •]. An extended pulsed regimen of fidaxomicin, like for vancomycin, is also suggested.…”

Section: New Developments In Treatment Options and Future Directionsmentioning

confidence: 99%

Updates and Opinions in Diagnosis and Treatment of Clostridiodes difficile in Pediatrics

Malhotra

Mohandas

2021

Curr Treat Options Peds

View full text Add to dashboard Cite

Purpose of review Clostridiodes difficile infection (CDI) has unique challenges for diagnosis and treatment in pediatrics. Though new antibiotics and biologics are being approved or developed for adults, most of the pediatric therapies still rely on multiple or extended antibiotic courses. This review aims to highlight emerging evidence and our clinical experience with CDI in children and can help inform readers’ approach to pediatric CDI. Recent findings Use of fidaxomicin for CDI in pediatrics has been shown to be to be non-inferior to vancomycin and is associated with higher global cure rates and decreased risk of recurrence. Fecal microbiota transplant is a successful emerging therapy with cure rates of up to 90%, though safety alerts should be noted. Diagnostic laboratory testing for C. difficile remains a challenge as it still cannot definitively distinguish between colonization and true infection, and this is particularly relevant to pediatric patients as they have the highest rates of colonization. Summary The diagnosis and treatment of C. difficile infection in pediatrics remain challenging and recommendations lag behind advances made in the adult field. Recent data suggests that use of fidaxomicin both as treatment of first episode or recurrences may be beneficial in pediatrics just as in adults. At an experienced center, FMT is associated with high cure rates. Bezlotuxumab a monoclonal antibody to toxin B that is already recommended for use in adults is being studied in children and should be available for clinical use soon. Oral vancomycin prophylaxis is also an emerging strategy for high-risk patients. Finally, a possible vaccine may be on the horizon for pediatrics.

show abstract

Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults

Cited by 359 publications

References 35 publications

Initial vancomycin versus metronidazole for the treatment of first-episode non-severe Clostridioides difficile infection

Initial vancomycin versus metronidazole for the treatment of first-episode non-severe Clostridioides difficile infection

Fidaxomicin as first line: What will it cost in the USA and Canada?

Updates and Opinions in Diagnosis and Treatment of Clostridiodes difficile in Pediatrics

Contact Info

Product

Resources

About