Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections

a meta-analysis and indirect treatment comparison

Oliver A. Cornely (Lead / Corresponding author), Dilip Nathwani, Cristina Ivanescu, Olatunji Odufowora-Sita, Peny Retsa, Isaac A. O. Odeyemi

    Research output: Contribution to journalArticle

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    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.

    Original languageEnglish
    Pages (from-to)2892-2900
    Number of pages9
    JournalJournal of Antimicrobial Chemotherapy
    Volume69
    Issue number11
    DOIs
    Publication statusPublished - Nov 2014

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    Clostridium Infections
    Clostridium difficile
    Metronidazole
    Vancomycin
    Meta-Analysis
    Therapeutics
    lipiarmycin
    Recurrence

    Cite this

    Cornely, Oliver A. ; Nathwani, Dilip ; Ivanescu, Cristina ; Odufowora-Sita, Olatunji ; Retsa, Peny ; Odeyemi, Isaac A. O. / Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections : a meta-analysis and indirect treatment comparison. In: Journal of Antimicrobial Chemotherapy. 2014 ; Vol. 69, No. 11. pp. 2892-2900.
    @article{196d53b5fa274fac897835ea6de7a972,
    title = "Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections: a meta-analysis and indirect treatment comparison",
    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.",
    author = "Cornely, {Oliver A.} and Dilip Nathwani and Cristina Ivanescu and Olatunji Odufowora-Sita and Peny Retsa and Odeyemi, {Isaac A. O.}",
    note = "{\circledC} The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.",
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    Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections : a meta-analysis and indirect treatment comparison. / Cornely, Oliver A. (Lead / Corresponding author); Nathwani, Dilip; Ivanescu, Cristina; Odufowora-Sita, Olatunji; Retsa, Peny; Odeyemi, Isaac A. O.

    In: Journal of Antimicrobial Chemotherapy, Vol. 69, No. 11, 11.2014, p. 2892-2900.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections

    T2 - a meta-analysis and indirect treatment comparison

    AU - Cornely, Oliver A.

    AU - Nathwani, Dilip

    AU - Ivanescu, Cristina

    AU - Odufowora-Sita, Olatunji

    AU - Retsa, Peny

    AU - Odeyemi, Isaac A. O.

    N1 - © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

    PY - 2014/11

    Y1 - 2014/11

    N2 - 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.

    AB - 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.

    U2 - 10.1093/jac/dku261

    DO - 10.1093/jac/dku261

    M3 - Article

    VL - 69

    SP - 2892

    EP - 2900

    JO - Journal of Antimicrobial Chemotherapy

    JF - Journal of Antimicrobial Chemotherapy

    SN - 0305-7453

    IS - 11

    ER -