Tag Archives: C diff

Clostridioides difficile Treatment in 2026

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P Feuerstadt et al. AJG 2025; 120: 2468-2470. Treatment of Clostridioides difficile: The Times They Are Changing

This article summarizes the recent changes in the treatment options for Clostridioides difficile (C diff).

Key points:

  • Fidaxomicin targets C diff with limited collateral microbiome disruption. This leads to significantly lower recurrence rates compared to vancomycin. Thus, it is preferred 1st line therapy for initial and recurrent C diff. In “the coming years, fidaxomicin is expected to come off patents” which will improve access and affordability.
  • Bexlotoxumab which lowered recurrence rate is no longer being produced
  • FMT via Openbiome is no longer available. In those in which FMT was used, options include the following:
  1. live-jslm (REBYOTA), a broad consortium enema-based formulation
  2. live-brpk (VOWST), a narrow consortium of Firmicutes in an encapsulated form. This treatment in adults: four capsules daily for three days
  3. Both treatments are not recommended for patients who are severely immunocompromised. In these patients, prolonged vancomycin course with taper or using every other day therapy with fidaxomicin for days 7-25 could be considered

My take: I have been seeing less C diff cases recently. This may be due to better antibiotic stewardship, changes in C diff strains, or improved testing approaches.. My observation is supported by recent reports:

AY Guh et al. Infect Dis Clin North Am. 2025. 39:567-580. Changes in the Epidemiology of Clostridioides difficile Infection

Annual number of hospitalized community-onset and hospital-onset CDI events reported to the National Healthcare Safety Network, 2015 to 2023. (From CDC’s Antibiotic Resistance & Patient Safety Portal (Available at https://arpsp.cdc.gov/profile/nhsn/cdi).)

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Fidaxomicin Treatment of Clostridioides difficile in Children and Adolescents

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MA Conrad et al. The Journal of Pediatrics, Volume 285, 114681. Open Access! Fidaxomicin Treatment of Clostridioides difficile Infections and Recurrences in Children and Adolescents: A Retrospective Multicenter Study

Methods: This was a  a multicenter, retrospective, observational study of fidaxomicin treatment for primary or recurrent CDI in children ages 12 months to 18 years old identified from 2013 to 2021 at 5 centers. Inclusion criteria were active CDI, defined as ≥3 watery stools in 24 hours and a positive laboratory test (toxin enzyme immunoassay positivity and/or polymerase chain reaction [PCR] positivity). Cure was defined as resolution of symptoms.

Patient characteristics:

  • Of the 95 patients included in this study, 84 (88%) were treated with fidaxomicin for a recurrent CDI, and 82 (86%) had at least one medical or surgical comorbidity.  
  • 38 (40%) patients had 4 or more CDI prior to fidaxomicin.
  • 22 (23%) had prior FMT.
  • 29 (31%) had IBD

Key findings:

  • By day 14 (end of treatment): 50 patients (52.6%) had a clinical cure and an additional 29 (30.5%) had improvement of symptoms. Thus, 17% did not respond to treatment.
  • Among 79 patients who responded to fidaxomicin treatment, 17 (21.5%) had a clinical and microbiologically confirmed recurrence of CDI by day 60, likely representing relapse.
  • Patients with inflammatory bowel disease were less likely to achieve clinical cure at day 14 (OR 0.27). 9 of 29 were considered treatment failures.
  • If the patient’s with IBD are excluded (n=66), there were only 7 (11%) treatment failures

Discussion points:

  • “Our clinical experience is that approval for coverage by insurers often is restricted to those with recurrent CDI, and the cost of fidaxomicin may limit availability for use as primary therapy.”
  • “CDI in IBD is a major clinical conundrum as the symptoms of the 2 disorders can overlap, and a positive C. difficile test is not always indicative of its active pathologic role…Therefore, patients who undergo treatment for CDI without response likely have an alternative cause of symptoms…. Current guidelines recommend reassessing symptoms in patients
    with IBD being treated for CDI at day 3 or 4 of the treatment course in order to consider escalation of IBD therapy in those who are not responding clinically to antimicrobial therapy.”

My take (borrowed from the authors): “More extensive studies are necessary to understand how to position fidaxomicin in the treatment algorithm for pediatric CDI.”

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Secondary Prophylaxis of Clostridiodes difficile Infection

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H Bao et al. Pediatrics 2021; 148: e2020031807. Oral Vancomycin as Secondary Prophylaxis for Clostridioides difficile Infection. Thanks to Ben Gold for sharing this reference.

Methods: A multicampus, retrospective cohort evaluation was conducted among patients aged ≤18 years with any history of clinical CDI and receiving systemic antibiotics in a subsequent encounter from 2013–2019. This study identified 30 and 44 patients received oral vancomycin prophylaxis (OVP) and no OVP, respectively. Eligible patients had to be >12 months of age and having at 3 unformed stools everyday.

OVP dosing: “vancomycin doses of 10 mg/kg (up to 125 mg per dose) every 12 hours during concomitant antibiotic use. OVP duration was intended to continue while on systemic antimicrobial agents and for 5 days after completion of antimicrobial agents (extended prophylaxis tail), but practice varied, and duration was ultimately left to the discretion of the provider.”

Key finding:

The incidence of CDI recurrence within 8 weeks of antibiotic exposure was significantly lower in patients who received OVP (3% vs 25%; P = .02) despite this group having notably more risk factors for recurrence.   After adjustment in a multivariable analysis, secondary OVP was associated with less risk of recurrence (odds ratio, 0.10; 95% confidence interval, 0.01–0.86; P = .04).

This study is in agreement with studies in adults (Brown CC, et al. Oral Vancomycin for Secondary Prophylaxis of Clostridium difficile Infection. Ann Pharmacother. 2019 Apr;53(4):396-401). In this review, the authors state: “Variable dosing regimens and lack of safety data are limitations.. clinicians can consider vancomycin 125 mg orally once or twice daily in high-risk patients receiving broad-spectrum antibacterial agents.”

My take: In patients at high risk of recurrent CDI, OVP should be considered as secondary prophylaxis when receiving systemic antibiotics.

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