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Infection

, Volume 45, Issue 4, pp 425–431 | Cite as

Fidaxomicin for treatment of Clostridium difficile infection in clinical practice: a prospective cohort study in a French University Hospital

  • Marie Pichenot
  • Rozenn Héquette-Ruz
  • Remi Le Guern
  • Bruno Grandbastien
  • Clément Charlet
  • Frédéric Wallet
  • Sophie Schiettecatte
  • Fanny Loeuillet
  • Benoit Guery
  • Tatiana Galperine
Original Paper

Abstract

Purpose

Two randomized controlled trials (RCTs) showed the non-inferiority of fidaxomicin compared with vancomycin for Clostridium difficile infection (CDI) treatment and its superiority regarding recurrence rate. The aim of this study was to evaluate fidaxomicin’s efficacy in clinical practice.

Methods

This single-center prospective cohort study included hospitalized patients treated with fidaxomicin for CDI. Demographic, clinical and biological data were collected. Primary outcome was efficacy of fidaxomicin (clinical cure, recurrence and global cure) at 10 weeks. Secondary outcome was efficacy among different subgroups.

Results

Ninety-nine patients were included: 42 severe CDI, 16 complicated CDI and 41 recurrent CDI. Rates of clinical cure, recurrence and global cure were 87, 15 and 59%, respectively. Subgroup analysis showed a higher recurrence rate for patients with recurrent CDI compared with first episode (8 vs. 26%; p = 0.04). Binary toxin was associated with severe/complicated CDI (80 vs. 50%; p < 0.01) and recurrence (32 vs. 7%; p < 0.01). Fidaxomicin was used as a first line for 83% of the patients with recurrence and for only 52% of first episodes even though 86% had recurrence’s risk factors.

Conclusion

Compared with RCTs, fidaxomicin in real world is used for patients with more severe and recurrent CDI, but clinical cure and recurrence rates were similar. Comparative studies are needed in these specific subgroups. Our data also illustrate clinicians’ difficulty to define a “patient at risk for recurrence” among the first episodes. Finally, we showed that binary toxin could be important in the screening for severity and recurrence risks.

Keywords

Fidaxomicin Clostridium difficile Prospective Clinical practice 

Notes

Compliance with ethical standards

Conflict of interest

The authors decline conflicts of interest regarding this work and did not receive external funding.

References

  1. 1.
    Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372:825–34.CrossRefPubMedGoogle Scholar
  2. 2.
    Wiegand PN, Nathwani D, Wilcox MH, Stephens J, Shelbaya A, Haider S. Clinical and economic burden of Clostridium difficile infection in Europe: a systematic review of healthcare-facility-acquired infection. J Hosp Infect. 2012;81:1–14.CrossRefPubMedGoogle Scholar
  3. 3.
    Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370:1198–208.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Davies KA, Longshaw CM, Davis GL, et al. Underdiagnosis of Clostridium difficile across Europe: the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID). Lancet Infect Dis. 2014;14:1208–19.CrossRefPubMedGoogle Scholar
  5. 5.
    Ferrer Márquez M, Hernández Martínez Á, Reina Duarte Á, Rosado Cobián R. Current status of the treatment of fulminant colitis. Cir Esp. 2015;93:276-82.CrossRefPubMedGoogle Scholar
  6. 6.
    Hensgens MPM, Dekkers OM, Goorhuis A, LeCessie S, Kuijper EJ. Predicting a complicated course of Clostridium difficile infection at the bedside. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2014;20:O301–8.Google Scholar
  7. 7.
    Taori SK, Wroe A, Poxton IR. Clostridium difficile infections in South East Scotland: mortality and recurrence in a region without PCR ribotype 027. J Med Microbiol. 2013;62:1468–77.CrossRefPubMedGoogle Scholar
  8. 8.
    Le Monnier A, Duburcq A, Zahar J-R, et al. Hospital cost of Clostridium difficile infection including the contribution of recurrences in French acute-care hospitals. Infect: J Hosp; 2015.Google Scholar
  9. 9.
    Olsen MA, Yan Y, Reske KA, Zilberberg MD, Dubberke ER. Recurrent Clostridium difficile infection is associated with increased mortality. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2015;21:164–70.Google Scholar
  10. 10.
    Sheitoyan-Pesant C, Abou Chakra CN, Pépin J, Marcil-Héguy A, Nault V, Valiquette L. Clinical and healthcare burden of multiple recurrences of Clostridium difficile infection. Clin Infect Dis Off Publ Infect Dis Soc Am. 2016;62:574–80.CrossRefGoogle Scholar
  11. 11.
    Barbut F, Richard A, Hamadi K, Chomette V, Burghoffer B, Petit JC. Epidemiology of recurrences or reinfections of Clostridium difficile-associated diarrhea. J Clin Microbiol. 2000;38:2386–8.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Deshpande A, Pasupuleti V, Thota P, et al. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2015;36:452–60.CrossRefPubMedGoogle Scholar
  13. 13.
    D’Agostino RB, Collins SH, Pencina KM, Kean Y, Gorbach S. Risk estimation for recurrent Clostridium difficile infection based on clinical factors. Clin Infect Dis Off Publ Infect Dis Soc Am. 2014;58:1386–93.CrossRefGoogle Scholar
  14. 14.
    Abou Chakra CN, Pepin J, Sirard S, Valiquette L. Risk factors for recurrence, complications and mortality in Clostridium difficile infection: a systematic review. PLoS One. 2014;9:e98400.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Bacci S, Mølbak K, Kjeldsen MK, Olsen KEP. Binary toxin and death after Clostridium difficile infection. Emerg Infect Dis. 2011;17:976–82.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Stewart DB, Berg A, Hegarty J. Predicting recurrence of C. difficile colitis using bacterial virulence factors: binary toxin is the key. J Gastrointest Surg Off J Soc Surg Aliment Tract. 2013;17:118–24 (discussion 124–125).CrossRefGoogle Scholar
  17. 17.
    Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2012;18:21–7.Google Scholar
  18. 18.
    Zar FA, Bakkanagari SR, Moorthi KMLST, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis Off Publ Infect Dis Soc Am. 2007;45:302–7.CrossRefGoogle Scholar
  19. 19.
    Babakhani F, Bouillaut L, Gomez A, Sears P, Nguyen L, Sonenshein AL. Fidaxomicin inhibits spore production in Clostridium difficile. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012;55:S162–9.CrossRefGoogle Scholar
  20. 20.
    Babakhani F, Gomez A, Robert N, Sears P. Killing kinetics of fidaxomicin and its major metabolite, OP-1118, against Clostridium difficile. J Med Microbiol. 2011;60:1213–7.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Louie TJ, Cannon K, Byrne B, et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012;55:S132–42.CrossRefGoogle Scholar
  22. 22.
    Cornely OA, Crook DW, Esposito R, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012;12:281–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422–31.CrossRefPubMedGoogle Scholar
  24. 24.
    Debast SB, Bauer MP, Kuijper EJ. Committee. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2014;20:1–26.Google Scholar
  25. 25.
    Khanafer N, Barbut F, Eckert C, et al. Factors predictive of severe Clostridium difficile infection depend on the definition used. Anaerobe. 2016;37:43–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Jacobson SM, Slain D. Evaluation of a bedside scoring system for predicting clinical cure and recurrence of Clostridium difficile infections. Am J Health Syst Pharm AJHP Off J Am Soc Health Syst Pharm. 2015;72:1871–5.CrossRefGoogle Scholar
  27. 27.
    Eiland EH, Sawyer AJ, Massie NL. Fidaxomicin use and clinical outcomes for Clostridium difficile-associated diarrhea. Infect Dis Clin. Pract Baltim Md. 2015;23:32–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Vargo CA, Bauer KA, Mangino JE, Johnston JEW, Goff DA. An antimicrobial stewardship program’s real-world experience with fidaxomicin for treatment of Clostridium difficile infection: a case series. Pharmacotherapy. 2014;34:901-9.CrossRefPubMedGoogle Scholar
  29. 29.
    Fehér C, Múñez Rubio E, Merino Amador P, et al. The efficacy of fidaxomicin in the treatment of Clostridium difficile infection in a real-world clinical setting: a Spanish multi-centre retrospective cohort. Eur J Clin Microbiol Infect Dis. 2016. [Epub ahead of print].Google Scholar
  30. 30.
    Goldenberg SD, Brown S, Edwards L, et al. The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 2016;35:251–9.CrossRefGoogle Scholar
  31. 31.
    Esmaily-Fard A, Tverdek FP, Crowther DM, Ghantoji SS, Adachi JA, Chemaly RF. The use of fidaxomicin for treatment of relapsed Clostridium difficile infections in patients with cancer. Pharmacotherapy. 2014;34:1220-5.CrossRefPubMedGoogle Scholar
  32. 32.
    Orenstein R. Fidaxomicin failures in recurrent Clostridium difficile infection: a problem of timing. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012;55:613–4.CrossRefGoogle Scholar
  33. 33.
    Johnson S, Gerding DN. Fidaxomicin ‘chaser’ regimen following vancomycin for patients with multiple Clostridium difficile recurrences. Clin Infect Dis Off Publ Infect Dis Soc Am. 2013;56:309–10.CrossRefGoogle Scholar
  34. 34.
    Hu MY, Katchar K, Kyne L, et al. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology. 2009;136:1206–14.CrossRefPubMedGoogle Scholar
  35. 35.
    Sailhamer EA, Carson K, Chang Y, et al. Fulminant Clostridium difficile colitis: patterns of care and predictors of mortality. Arch Surg. 2009;144:433–9 (discussion 439–440).Google Scholar
  36. 36.
    Penziner S, Dubrovskaya Y, Press R, Safdar A. Fidaxomicin therapy in critically ill patients with Clostridium difficile infection. Antimicrob Agents Chemother. 2015;59:1776–81.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    van Kleef E, Green N, Goldenberg SD, et al. Excess length of stay and mortality due to Clostridium difficile infection: a multi-state modelling approach. J Hosp Infect. 2014;88:213–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Dubberke ER, Butler AM, Reske KA, et al. Attributable outcomes of endemic Clostridium difficile-associated disease in nonsurgical patients. Emerg Infect Dis. 2008;14:1031–8.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Pépin J, Valiquette L, Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. CMAJ Can Med Assoc J J Assoc Med Can. 2005;173:1037–42.CrossRefGoogle Scholar
  40. 40.
    Reigadas E, Alcalá L, Marín M, Martín A, Iglesias C, Bouza E. Role of binary toxin in the outcome of Clostridium difficile infection in a non-027 ribotype setting. Epidemiol Infect. 2016;144:268–73.CrossRefPubMedGoogle Scholar
  41. 41.
    Pilate T, Verhaegen J, Van Ranst M, Saegeman V. Binary toxin and its clinical importance in Clostridium difficile infection, Belgium. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 2016;35:1741–7.CrossRefGoogle Scholar
  42. 42.
    Goldenberg SD, French GL. Lack of association of tcdC type and binary toxin status with disease severity and outcome in toxigenic Clostridium difficile. J Infect. 2011;62:355–62.CrossRefPubMedGoogle Scholar
  43. 43.
    Watt M, McCrea C, Johal S, Posnett J, Nazir J. A cost-effectiveness and budget impact analysis of first-line fidaxomicin for patients with Clostridium difficile infection (CDI) in Germany. Infection. 2016;44:599–606.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Nathwani D, Cornely OA, Van Engen AK, Odufowora-Sita O, Retsa P, Odeyemi IAO. Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection. J Antimicrob Chemother. 2014;69:2901–12.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Rubio-Terrés C, Cobo Reinoso J, Grau Cerrato S, et al. Economic assessment of fidaxomicin for the treatment of Clostridium difficile infection (CDI) in special populations (patients with cancer, concomitant antibiotic treatment or renal impairment) in Spain. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 2015;34:2213–23.CrossRefGoogle Scholar
  46. 46.
    Planche TD, Davies KA, Coen PG, et al. Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C difficile infection. Lancet Infect Dis. 2013;13:936–45.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Polage CR, Gyorke CE, Kennedy MA, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med. 2015;175:1792–801.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Kok J, Wang Q, Thomas LC, Gilbert GL. Presumptive identification of Clostridium difficile strain 027/NAP1/BI on Cepheid Xpert: interpret with caution. J Clin Microbiol. 2011;49:3719–21.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Marie Pichenot
    • 1
  • Rozenn Héquette-Ruz
    • 1
  • Remi Le Guern
    • 2
  • Bruno Grandbastien
    • 2
  • Clément Charlet
    • 1
  • Frédéric Wallet
    • 3
  • Sophie Schiettecatte
    • 4
  • Fanny Loeuillet
    • 4
  • Benoit Guery
    • 1
    • 5
  • Tatiana Galperine
    • 1
  1. 1.Department of Infectious DiseasesUniversité Lille Nord de FranceLilleFrance
  2. 2.Department of Infection Risk ManagementUniversité Lille Nord de FranceLilleFrance
  3. 3.Institute of MicrobiologyUniversité Lille Nord de FranceLilleFrance
  4. 4.Department of PharmacyUniversité Lille Nord de FranceLilleFrance
  5. 5.Infectious Diseases Service, Centre Hospitalier Universitaire VaudoisUniversity of LausanneLausanneSwitzerland

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