Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections: a meta-analysis and indirect treatment comparison

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). A systematic literature review was conducted in July to August 2011 and updated in July 2013. For fi...

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Bibliographic Details
Published in:	Journal of antimicrobial chemotherapy 2014-11, Vol.69 (11), p.2892-2900
Main Authors:	Cornely, Oliver A, Nathwani, Dilip, Ivanescu, Cristina, Odufowora-Sita, Olatunji, Retsa, Peny, Odeyemi, Isaac A O
Format:	Article
Language:	eng
Subjects:	Aminoglycosides - therapeutic use Anti-Bacterial Agents - therapeutic use Antibiotics Bacteria Clinical Trials, Phase III as Topic - methods Clostridium difficile - drug effects Clostridium Infections - diagnosis Clostridium Infections - drug therapy Comparative analysis Enterocolitis, Pseudomembranous - diagnosis Enterocolitis, Pseudomembranous - drug therapy Humans Medical treatment Meta-analysis Metronidazole - therapeutic use Treatment Outcome Vancomycin - therapeutic use
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Summary:	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). 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. 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. 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.
ISSN:	0305-7453 1460-2091