Decreased warfarin effects in elder with recurrent Clostridium difficile infection during fidaxomicin therapy: a case report

Antonio Riccardo Buonuomo, Maria Alessandra Foggia, Emanuela Zappulo, Guglielmo Borgia, Ivan Gentile



Clostridium difficile infection is a disease with increasing incidence, particularly in high‑riskpatients such as the elderly, immunocompromised patients, etc.

We report an unexpected decrease of International Normalized Ratio (INR) response to warfarin during a first recurrence of Clostridium difficile infection (CDI) treated with fidaxomicin. The patient, an old man who has prosthetic heart valves on anticoagulation therapy with warfarin, was treated with an association of vancomycin plus metronidazole for a first episode of CDI. Patient remained symptom‑free for few days and then he presented with recurrent diarrhea. A retreatment with vancomycin and metronidazole didn’t resolve symptoms of CDI, therefore he underwent fidaxomicin treatment for 10 days, with rapid resolution of diarrhea. In the meantime, warfarin effects diminished, and only with increases of dosage INR therapeutic range was achieved few days after discontinuing fidaxomicin. According to product information, fidaxomicin doesn’t interfere with warfarin. The authors highlight the different plausible mechanisms to explain the association between the unexpected decreased effect of warfarin and factors that could have influenced such event. The frequent update of product information through good pharmacovigilance practices could help clinicians in the management of unexpected events.


Clostridium difficile infection; Warfarin; Fidaxomicin; Vitamin K

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  • Di Bella S, Musso M, Cataldo MA, et al. Clostridium difficile infection in Italian urban hospitals: data from 2006 through 2011. BMC Infect Dis 2013; 13: 146;
  • Bassetti M, Villa G, Pecori D, et al. Epidemiology, diagnosis and treatment of Clostridium difficile infection. Expert Rev Anti Infect Ther 2012; 10: 1405-23;
  • Società Italiana Multidisciplinare per la Prevenzione delle Infezioni nelle Organizzazioni Sanitarie. Prevenzione e controllo delle infezioni da Clostridium difficile. GIIO vol. 16 (1). Gennaio-Marzo 2009
  • Dupont HL. Diagnosis and management of Clostridium difficile infection. Clin Gastroenterol Hepatol 2013; 11: 1216-23;
  • Dificlir TM (fidaxomicina). Riassunto delle Caratteristiche del Prodotto (revisione 06/2013)
  • Debast SB, Bauer MP, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect 2014; 20 (S2): 1-26;
  • Cornely OA, Crook DW, Esposito R, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomized controlled trial. Lancet Infect Dis 2012; 12: 281-9;
  • Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011; 364: 422-31;
  • Duggan ST. Fidaxomicin: in Clostridium difficile infection. Drugs 2011; 71: 2445-56;
  • Cruz MP. Fidaxomicin (Dificid), a novel oral macrocyclic antibacterial agent for the treatment of Clostridium difficile-associated diarrhea in adults. P T 2012; 37: 278-81
  • Brunton LL, Lazo JS, Parker KL. Oral anticoagulants. In: Goodman & Gilman’s. The pharmacological basis of Therapeutics. Eleventh edition. Chapter 54, pages 1475-80
  • Maeda T, Tsukui H, Umehara N, et al. Warfarin effects diminishment by the Clostridium butyricum preparation after cardiac surgery; report of a case. Kyobu Geka 2014; 67: 505-7


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