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Antimicrobial Agents and Chemotherapy, September 2006, p. 3028-3032, Vol. 50, No. 9
0066-4804/06/$08.00+0     doi:10.1128/AAC.00019-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Frequent Emergence of Resistance in Clostridium difficile during Treatment of C. difficile-Associated Diarrhea with Fusidic Acid

Department of Infectious Diseases, Örebro University Hospital, Örebro,¹ Infectious Diseases Research Unit, Department of Clinical Sciences, Lund University, Malmö,² Swedish Institute for Infectious Disease Control, Solna,³ Department of Clinical Medicine, Örebro University, Örebro, Sweden⁴

Received 6 January 2006/ Returned for modification 5 March 2006/ Accepted 30 June 2006

Samples from patients with Clostridium difficile-associated diarrhea (CDAD) that were randomized to fusidic acid (n = 59) or metronidazole (n = 55) therapy for 7 days were cultured for Clostridium difficile in feces on days 1, 8 to 13, and 35 to 40. Of the patients who were culture positive only before treatment, 77% (36/47) were permanently cured (no treatment failure and no clinical recurrence), compared to 54% (22/41) of those with persistence of C. difficile at one or both follow-ups (P = 0.03). A similar association between bacterial persistence and a worse outcome of therapy was seen in both treatment groups. Resistance to fusidic acid was found in 1 of 88 pretherapy isolates available, plus in at least 1 subsequent isolate from 55% (11/20) of patients who remained culture-positive after fusidic acid therapy. In 10 of these 11 patients, the resistant follow-up isolate(s) belonged to the same PCR ribotype as the susceptible day 1 isolate, confirming frequent emergence of resistance to fusidic acid during treatment. Despite this, 5 of these 11 patients were permanently cured with fusidic acid, relative to 5 of 9 patients with susceptible C. difficile at follow-up (P = 1.0). None of the 36 PCR ribotypes of C. difficile identified was associated with any particular clinical outcome or emergence of fusidic acid resistance. In conclusion, culture positivity for C. difficile was common after both fusidic acid and metronidazole therapy and was associated with treatment failure or recurrence of CDAD. Development of resistance in C. difficile was frequent in patients given fusidic acid, but it was without apparent negative impact on therapeutic efficacy in the actual CDAD episode.

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