• Kathleen M Mullane, Mark A Miller, Karl Weiss, Arnold Lentnek, Yoav Golan, Pamela S Sears, Youe-Kong Shue, Thomas J Louie, and Sherwood L Gorbach.
• Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. kmullane@medicine.bsd.uchicago.edu
• Clin. Infect. Dis. 2011 Sep 1;53(5):440-7.

BackgroundTreatment guidelines recommend stopping all implicated antibiotics at the onset of Clostridium difficile infection (CDI), but many individuals have persistent or new infections necessitating the use of concomitant antibiotics (CAs). We used data from 2 phase 3 trials to study effects of CAs on response to fidaxomicin or vancomycin.MethodsSubjects with CDI were treated for 10 days with fidaxomicin 200 mg every 12 hours or vancomycin 125 mg every 6 hours, assessed for resolution of symptoms, and followed up for an additional 4 weeks for evidence of recurrence. Rates of cure, recurrence, and global cure (cure without recurrence) were determined for subgroups of subjects defined by CA use and treatment group.ResultsCAs were prescribed for 27.5% of subjects during study participation. The use of CAs concurrent with CDI treatment was associated with a lower cure rate (84.4% vs 92.6%; P < .001) and an extended time to resolution of diarrhea (97 vs 54 hours; P < .001). CA use during the follow-up was associated with more recurrences (24.8% vs 17.7%; not significant), and CA administration at any time was associated with a lower global cure rate (65.8% vs 74.7%; P = .005). When subjects received CAs concurrent with CDI treatment, the cure rate was 90.0% for fidaxomicin and 79.4% for vancomycin (P = .04). In subjects receiving CAs during treatment and/or follow-up, treatment with fidaxomicin compared with vancomycin was associated with 12.3% fewer recurrences (16.9% vs 29.2%; P = .048).ConclusionsTreatment with CAs compromised initial response to CDI therapy and durability of response. Fidaxomicin was significantly more effective than vancomycin in achieving clinical cure in the presence of CA therapy and in preventing recurrence regardless of CA use.

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