Guidelines: Antibiotics for All but Very Mild C difficile

Laurie Barclay, MD

October 30, 2013

On October 29, the European Society of Clinical Microbiology and Infection (ESCMID) issued updated guidelines forClostridium difficile infection (CDI), reviewing treatment options of antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, and fecal or bacterial intestinal transplantation. The new recommendations, published onlineOctober 5 in Clinical Microbiology and Infection, advise antibiotic treatment for all but very mild cases of CDI.

CDI, which is potentially fatal, is now the leading cause of healthcare-acquired infections in hospitals, having surpassed methicillin-resistant Staphylococcus aureus.

"[A]fter the recent development of new alternative drugs for the treatment of CDI (e.g. fidaxomicin) in US and Europe, there has been an increasing need for an update on the comparative effectiveness of the currently available antibiotic agents in the treatment of CDI, thereby providing evidence-based recommendations on this issue," write Sylvia B. Debast, from the Centre for Infectious Diseases, Leiden University Medical Center The Netherlands, and colleagues from the ESCMID Committee.

The new guideline, which updates the 2009 ESCMID recommendations now used widely in clinical practice, summarizes currently available CDI treatment options and offers updated treatment recommendations on the basis of a literature search of randomized and nonrandomized trials.

The ESCMID and an international team of experts from 11 European countries developed recommendations for different patient subgroups, including initial nonsevere disease, severe CDI, first recurrence or risk for recurrent disease, multiple recurrences, and treatment of CDI when patients cannot receive oral antibiotics.

Antibiotic Recommended in Most Cases

Specific recommendations include the following:

• For nonepidemic, nonsevere CDI clearly induced by antibiotic use, with no signs of severe colitis, it may be acceptable to stop the inducing antibiotic and observe the clinical response for 48 hours. However, patients must be monitored very closely and treated immediately for any signs of clinical deterioration.
• Antibiotic treatment is recommended for all cases of CDI except for very mild CDI, which is actually triggered by antibiotic use. Suitable antibiotics include metronidazole, vancomycin, and fidaxomicin, a newer antibiotic that can be given by mouth.
• For mild/moderate disease, metronidazole is recommended as oral antibiotic treatment of initial CDI (500 mg 3 times daily for 10 days).
• Fidaxomicin may be used in all CDI patients for whom oral antibiotic treatment is appropriate. Specific indications for fidaxomicin may include first-line treatment in patients with first CDI recurrence or at risk for recurrent disease, in patients with multiple recurrences of CDI, and in patients with severe disease and nonsevere CDI.

These recommendations were based on 2 large phase 3 clinical studies that compared 400 mg/day oral fidaxomicin with 500 mg/day oral vancomycin, the standard of care. The rate of CDI recurrence was lower with fidaxomicin, but the cure rate was similar for both treatments.

• For severe CDI, suitable oral antibiotic regimens are vancomycin 125 mg 4 times daily (may be increased to 500 mg 4 times daily) for 10 days, or fidaxomicin 200 mg twice daily for 10 days.
• In life-threatening CDI, there is no evidence supporting the use of fidaxomicin.
• In severe CDI or life-threatening disease, the use of oral metronidazole is strongly discouraged.
• For multiple recurrent CDI, fecal transplantation is strongly recommended.
• Total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended for CDI with colonic perforation and/or systemic inflammation and deteriorating clinical condition despite antibiotic treatment.
• Additional measures for CDI management include discontinuing unnecessary antimicrobial therapy, adequate fluid and electrolyte replacement, avoiding antimotility medications, and reviewing proton pump inhibitor use.

The authors have disclosed no relevant financial relationships.

Clin Microbiol Infect. Published online October 5, 2013. Abstract

M