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Updated: Jan 7, 2026

A Protocol to Characterize the Morphological Changes of Clostridium difficile in Response to Antibiotic Treatment
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Combination Therapy with Oral Vancomycin Plus Intravenous Metronidazole Is Not Superior to Oral Vancomycin Alone for

Young Wook Cho1,2, Jung Min Moon3,4, Hyeong Han Lee2,5

  • 1Department of Internal Medicine, Dongshin Hospital, Seoul 03653, Republic of Korea.

Antibiotics (Basel, Switzerland)
|December 30, 2025
PubMed

Insights

Combination therapy for severe Clostridioides difficile infection (CDI) using vancomycin and metronidazole did not improve outcomes. Vancomycin monotherapy showed a higher clinical cure rate in severe CDI patients.

Area of Science:

  • Infectious Diseases
  • Clinical Microbiology
  • Gastroenterology

Background:

  • Current guidelines recommend combination therapy for severe Clostridioides difficile infection (CDI).
  • Evidence supporting combination therapy for severe CDI is limited.
  • This study aimed to compare vancomycin monotherapy with combination therapy for severe CDI.

Purpose of the Study:

  • To compare clinical outcomes of vancomycin monotherapy versus combination therapy in severe CDI patients.
  • To evaluate the efficacy of combination therapy in reducing mortality, colectomy, and recurrence.
  • To assess the impact on clinical cure rates and length of hospital/ICU stay.

Main Methods:

  • Multicenter, retrospective, observational cohort study.
  • Included adult patients with severe CDI receiving oral vancomycin (Jan 2017 - May 2021).
  • Compared vancomycin monotherapy with combination therapy (vancomycin + IV metronidazole ≥72h).

Main Results:

  • No significant difference in 60-day mortality or colectomy between groups.
  • Similar recurrence rates, total length of stay, and ICU stay duration.
  • Vancomycin monotherapy demonstrated a significantly higher clinical cure rate (79.1% vs. 65.0%).

Conclusions:

  • Combination therapy with oral vancomycin and IV metronidazole is not associated with improved outcomes in severe CDI.
  • Vancomycin monotherapy may be a viable option for severe CDI, showing better cure rates.
  • Further prospective randomized trials are necessary to establish optimal treatment guidelines for severe CDI.
Keywords:
Clostridioides difficilemetronidazolevancomycin

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