Treatment of Clostridium difficile Infection

Disease Severity Classification

The Infectious Diseases Society of America recommends classifying disease severity as non-severe or severe, with non-severe CDI characterized by stool frequency <4 times daily and no signs of severe colitis 1, 2
Severe CDI is defined by the presence of one or more of the following: temperature >38.5°C, hemodynamic instability, leukocyte count >15×10⁹/L, serum creatinine rise >50% above baseline, elevated serum lactate, evidence of pseudomembranous colitis on endoscopy, or colonic wall thickening on imaging 2, 3, 4

The American College of Gastroenterology recommends vancomycin 125 mg four times daily orally for 10 days as first-line therapy for both non-severe and severe CDI 5, 6
For non-severe CDI, an alternative treatment is metronidazole 500 mg three times daily orally for 10 days, although this is less preferred 1, 7
For severe CDI, an alternative treatment is fidaxomicin 200 mg twice daily orally for 10 days, especially for patients at high risk of recurrence 5, 8

The Society for Healthcare Epidemiology of America recommends discontinuing the inciting antibiotic and observing clinical response in cases of mild CDI induced by antibiotics 1
Concomitant antibiotic use should be discontinued if possible, and agents less associated with CDI should be considered if continued antibiotic therapy is required 5, 6

The Infectious Diseases Society of America recommends treating the first recurrence based on severity, with consideration of fidaxomicin 200 mg twice daily for 10 days or vancomycin in a tapered and pulsed regimen 1, 7, 8
For second or subsequent recurrences, vancomycin 125 mg four times daily orally for at least 10 days, followed by a tapered and pulsed regimen, is recommended 2, 3
Fecal microbiota transplantation may be considered for multiple recurrences that have failed appropriate antibiotic treatments 8

Colectomy should be considered in cases of perforation of the colon, systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy, toxic megacolon, or severe ileus 2, 3, 7
Surgery should be performed before serum lactate exceeds 5.0 mmol/L 2, 4

The American College of Gastroenterology recommends discontinuing unnecessary proton pump inhibitors in patients at high risk for CDI 5, 6
Hand hygiene with soap and water is required, as alcohol-based hand sanitizers are ineffective against C. difficile spores 5, 6
Treatment duration may need to be extended beyond 10 days in patients with delayed response to therapy 8

For patients with fulminant CDI, oral vancomycin 500 mg four times daily for 10 days, plus intravenous metronidazole 500 mg every 8 hours, is recommended 9, 10
For patients with fulminant CDI and ileus, rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema is recommended 10

For second recurrence of CDI, vancomycin in a tapered and pulsed regimen is recommended 9, 10
For multiple recurrences of CDI, consider fecal microbiota transplantation after appropriate antibiotic treatment 9, 10

For children with non-severe CDI, metronidazole or vancomycin for 10 days is recommended 9
For children with severe or fulminant CDI, vancomycin orally or rectally every 8 hours, with or without metronidazole IV for 10 days, is recommended 9
For recurrent CDI in children, consider vancomycin extended regimen or fecal microbiota transplantation 9