title: Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections: a meta-analysis and indirect treatment comparison.
abstract: OBJECTIVE
  To evaluate the efficacy of fidaxomicin treatment, which has a limited effect on the normal gut flora, compared with vancomycin and metronidazole treatment in Clostridium difficile infections (CDIs).
  
  
  METHODS
  A systematic literature review was conducted in July to August 2011 and updated in July 2013. For fidaxomicin versus vancomycin, efficacy was evaluated using meta-analysis of data from two Phase III direct comparative studies (n = 1164). As there were no studies comparing fidaxomicin and metronidazole, an indirect comparison was made using data from three vancomycin versus metronidazole studies (n = 345), using the methodology of Bucher et al. (J Clin Epidemiol 1997; 50: 683-91). This provides an OR for the indirect comparison of fidaxomicin versus metronidazole when direct evidence of fidaxomicin versus vancomycin and vancomycin versus metronidazole is available.
  
  
  RESULTS
  Clinical cure rates were similar for fidaxomicin and vancomycin; the OR (95% CI) was 1.17 (0.82, 1.66). Recurrence [0.47 (0.34, 0.65)] was significantly lower and sustained cure rates [1.75 (1.35, 2.27)] significantly higher for fidaxomicin than vancomycin. Similar results were obtained in patient subgroups with severe CDI and with non-severe CDI. From the indirect comparison, the likelihood of recurrence [0.42 (0.18, 0.96)] and sustained cure [2.55 (1.44, 4.51)] were significantly improved for fidaxomicin versus metronidazole. Again, similar results were obtained in those with severe and non-severe CDI.
  
  
  CONCLUSIONS
  Fidaxomicin provides improved sustained cure rates in patients with CDI compared with vancomycin. An indirect comparison indicates that the same is also true for fidaxomicin versus metronidazole. In view of these data, fidaxomicin may be considered as first-line therapy for CDI.
authors: Department of Internal Medicine, Clinical Trials Centre Cologne, ZKS Köln, BMBF 01KN1106, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50924 Cologne, Germany oliver.cornely@zks-koeln.de.
authors: Oliver A
authors: OA
authors: Cornely
authors: Ninewells Hospital & Medical School, Dundee DD1 9SY, UK.
authors: Dilip
authors: D
authors: Nathwani
authors: Quintiles Consulting, Siriusdreef 10, 2132 WT Hoofddorp, The Netherlands.
authors: Cristina
authors: C
authors: Ivanescu
authors: Astellas Pharma Europe Ltd, 2000 Hillswood Drive, Chertsey, Surrey KT16 0RS, UK.
authors: Olatunji
authors: O
authors: Odufowora-Sita
authors: Astellas Pharma Europe Ltd, 2000 Hillswood Drive, Chertsey, Surrey KT16 0RS, UK.
authors: Peny
authors: P
authors: Retsa
authors: Astellas Pharma Europe Ltd, 2000 Hillswood Drive, Chertsey, Surrey KT16 0RS, UK.
authors: Isaac A O
authors: IA
authors: Odeyemi
mesh_terms: D000617:Aminoglycosides / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D016360:Clostridioides difficile / Q000187:drug effects*; D003015:Clostridium Infections / Q000175:diagnosis / Q000188:drug therapy*; D004761:Enterocolitis, Pseudomembranous / Q000175:diagnosis / Q000188:drug therapy; D000077732:Fidaxomicin; D006801:Humans; D008795:Metronidazole / Q000627:therapeutic use*; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D008795:Metronidazole; D014640:Vancomycin; D000077732:Fidaxomicin
keywords: C. difficile; CDIs; treatment