Oliver A Cornely1, Dilip Nathwani2, Cristina Ivanescu3, Olatunji Odufowora-Sita4, Peny Retsa4, Isaac A O Odeyemi4. 1. 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. 2. Ninewells Hospital & Medical School, Dundee DD1 9SY, UK. 3. Quintiles Consulting, Siriusdreef 10, 2132 WT Hoofddorp, The Netherlands. 4. Astellas Pharma Europe Ltd, 2000 Hillswood Drive, Chertsey, Surrey KT16 0RS, UK.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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: Stefan Hagel; Anne Fischer; Philipp Ehlermann; Thorsten Frank; Kester Tueffers; Andreas Sturm; Alexander Link; Muenevver Demir; Arno Siebenhaar; Martin Storr; Thomas Glueck; Erhard Siegel; Philip Solbach; Felix Goeser; Christian B. Koelbel; Ansgar Lohse; Christoph Luebbert; Ulrich Kandzi; Matthias Maier; Stefanie Schuerle; Markus M. Lerch; Daniela Tacke; Oliver A. Cornely; Andreas Stallmach; Maria Vehreschild Journal: Dtsch Arztebl Int Date: 2016-09-05 Impact factor: 5.594