Debate will brew about FIRST-LINE medications for C. difficile based on differing recommendations in new guidelines. Oral metronidazole has fallen out of favour, because it's less effective than vancomycin.
The American College of Gastroenterology now recommends either oral vancomycin or fidaxomicin for a first C. difficile episode. In contrast, updated Infectious Diseases Society of America (IDSA) guidelines suggest fidaxomicin (Dificid) over vancomycin, since fidaxomicin seems to have a slight edge at reducing recurrence.
For example, using fidaxomicin instead of vancomycin for 10 days seems to prevent recurrence in about 1 in 10 patients over 4 weeks. But IDSA leans heavily on data from hospitalized patients to support this change, and on studies with various fidaxomicin dosing strategies. And point out that using fidaxomicin instead of vancomycin does NOT improve resolution of diarrhea after completing the antibiotic, lead to fewer adverse effects or reduce mortality. Plus, cost and payer coverage of fidaxomicin is more and more than oral vancomycin.
Recommend sticking with oral vancomycin for initial treatment of C. difficile or as an extended taper for a recurrence in most patients. In general, save fidaxomicin as an option for patients with recurrent C. difficile, despite vancomycin. Continue to reserve metronidazole (Flagyl) for a mild initial infection if other medications aren't an option, such as due to cost. Caution that repeats metronidazole courses are linked to neurotoxicity (confusion, numbness, etc).
REFERENCES
Johnson S, Lavergne V, Skinner AM, Gonzales-Luna AJ, Garey KW, Kelly CP, Wilcox MH. 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. Clin Infect Dis. 2021 Jun 24:ciab549. Available at: https://pubmed.ncbi.nlm.nih.gov/34164674.
Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, Stollman NH. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol. 2021 Jun 1;116(6):1124-1147. Available at: https://pubmed.ncbi.nlm.nih.gov/34003176.
Guery B, Menichetti F, Anttila VJ, Adomakoh N, Aguado JM, Bisnauthsing K, Georgopali A, Goldenberg SD, Karas A, Kazeem G, Longshaw C, Palacios-Fabrega JA, Cornely OA, Vehreschild MJGT; EXTEND Clinical Study Group. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect Dis. 2018 Mar;18(3):296-307. Available at: https://pubmed.ncbi.nlm.nih.gov/29273269.
Mikamo H, Tateda K, Yanagihara K, Kusachi S, Takesue Y, Miki T, Oizumi Y, Gamo K, Hashimoto A, Toyoshima J, Kato K. Efficacy and safety of fidaxomicin for the treatment of Clostridioides (Clostridium) difficile infection in a randomized, double-blind, comparative Phase III study in Japan. J Infect Chemother. 2018 Sep;24(9):744-752. Available at: https://pubmed.ncbi.nlm.nih.gov/29934056