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Published on 30 October 2013

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New guidelines recommend Fixaxomicin

 

 

The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) has published new guidelines recommending fidaxomicin for all Clostridium Difficile infection (CDI) patients suitable for oral antibiotic treatment. Specifically the guidelines recommend fidaxomicin as first line therapy in CDI patients with first recurrence or risk for recurrent disease and in patients with multiple recurrences of CDI. The guidelines also recommend fidaxomicin in patients with severe disease and non-severe CDI.[3]
CDI is one of the most common causes of antibiotic-associated diarrhoea and severe cases can lead to bowel surgery and even death.[4] Hospital patients with CDI are up to three times more likely to die in hospital (or within a month of infection) than those without CDI.[5,6] Recurrence is a major challenge in CDI treatment. 25% of CDI patients suffer a recurrence within one month[7–9] and patients who have already had one recurrence have a 40% risk of a further episode of CDI.[10]
“One of the biggest challenges to optimal CDI management is recurrence, therefore the significant reduction in disease recurrence by DIFICLIR compared with vancomycin is an important step in reducing the morbidity and mortality associated with CDI”, comments Professor Oliver Cornely, University Hospital Cologne, Germany. “I welcome these guidelines and believe implementation of the recommendations will help to improve CDI care and reduce the burden on both patients and healthcare systems”.
Two large Phase III clinical studies comparing the efficacy and safety of 400mg/day oral fidaxomicin with 500mg/day oral vancomycin showed potential advantages of fidaxomicin over vancomycin, the standard of care.[9,11] Patients were eligible to participate in these trials with a confirmed diagnosis of CDI and included patients who were classified as having severe CDI as well as patients for whom CDI is an especial risk such as those patients who were elderly[11] or had concomitant diseases.[12–14]
Fidaxomicin significantly reduced the rate of CDI recurrence as compared with vancomycin, with patients treated with fidaxomicin significantly more likely than those receiving vancomycin to experience diarrhoea resolution without recurrence within 30 days of therapy completion.[9,11] Fidaxomicin also met its primary endpoint of clinical cure rate, which was equivalent to that of vancomycin.[9,11]
Certain populations are at higher risk of CDI and are particularly vulnerable. CDI can be associated with a mortality rate as high as 14% in elderly patients[15] and hospitalised cancer patients treated for CDI experience longer hospital stays.[16] Progressive chronic kidney disease is associated with increased time to resolution of diarrhoea, lower cure rates, and higher incidence of recurrence in patients treated for CDI.[14]
Patients in long term care facilities are particularly at risk and CDI recurrence rates can be as high as 50% over a six-month period when acquired in a long term care facility.[17] Mortality rates in intensive care unit patients over the age of 65 years have been reported to be as high as 45%.[18] In line with the revised ESCMID treatment guidance document DIFICLIR is recommended for patients who are suitable for oral antibiotic treatment in these vulnerable patient sub-populations.
“CDI is potentially fatal and has a major impact on patients’ health and quality of life. We hope adherence to these recommendations will lead to better management of CDI and the treatment of recurrence”, said Ken Jones, President and CEO of Astellas Pharma Europe Ltd.
The previous ESCMID guidance document was issued in 2009[19] and has been widely applied in clinical practice. However, as new CDI treatments have been developed an update of this document was necessary to further improve uniformity of national CDI treatment policies in hospitals across Europe. To produce the updated guidelines, ESCMID and a team of experts from 11 European countries ran a computerised literature search to review randomised and non-randomised trials investigating the effect of an intervention on the clinical outcome of CDI. The revised 2013 guidelines provide an overview of currently available CDI treatment options and evidence-based recommendations on the treatment of CDI.[3]
References
  1. Health Protection Agency. Quarterly Epidemiological Commentary: Mandatory MRSA, MSSA and E. coli bacteraemia, and C. difficile infection data (up to April–June 2013). 12 September 2013. Available from: http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317139835857 (last accessed 23 October 2013).
  2. Meyer E et al. Associations between nosocomial meticillin-resistant Staphylococcus aureus and nosocomial Clostridium difficile-associated diarrhoea in 89 German hospitals. J Hosp Infect 2012;82(3):181-6.
  3. Debast SB et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): update of the treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect. doi: 10.1111/1469-0691.12418.
  4. Ananthakrishnan AN. Clostridium difficile infection: epidemiology, risk factors and management. Nat Rev Gastroenterol Hepatol. 2011;8:17-26.
  5. Oake N, et al. The effect of hospital-acquired Clostridium difficile infection on in-hospital mortality. Arch Intern Med 2010;170:1804–10.
  6. Hensgens MP, et al. All-Cause and disease-specific mortality in hospitalized patients with Clostridium difficile infection: a Multicenter Cohort Study. Clin Infect Dis. 2013;56:1108–16.
  7. Lowy I, et al. Treatment with Monoclonal Antibodies against Clostridium difficile Toxins. N Engl J Med. 2010;362;3:197-205.
  8. Bouza E et al. Presented at 18th European Congress of Clinical Microbiology and Infectious Diseases, Barcelona 2008. Abstract0464.
  9. Louie TJ, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422–31.
  10. Kelly CP, LaMont JT. Clostridium difficile – more difficult than ever. N Engl J Med. 2008;359(18):1932−1940.
  11. Cornely OA 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;12:281-289.
  12. Cornely OA et al. Resolution of Clostridium difficile–Associated Diarrhea in Patients With Cancer Treated With Fidaxomicin or Vancomycin. J Clin Onc. 2013;31(19):2493-2499.
  13. Mullane KM et al. Efficacy of Fidaxomicin Versus Vancomycin as Therapy for Clostridium difficile Infection in Individuals Taking Concomitant Antibiotics for Other Concurrent Infections. Clin Infect Dis. 2011;53(5):440-447.
  14. Mullane KM et al. Renal impairment and clinical outcomes of Clostridium difficile infection in two randomized trials. Am J Nephrol. 2013;38(1):1–11.
  15. Loo VG et al. A predominantly clonal multiinstitutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005;353 (23):2442–2449.
  16. Campbell R et al. Length of stay and hospital costs among high-risk patients with hospital–origin Clostridium difficile-associated diarrhea. J. Med Econ. 2013;16(3):440–448.
  17. Kim JH et al. Clostridium difficile infection in a long-term care facility: hospital-associated illness compared with long-term care–associated illness. Infect Control Hosp Epidemiol. 2011;32(7):656–660.
  18. 18 Zilberberg MD et al. Clostridium difficile-associated disease and mortality among the elderly critically ill. Crit Care Med. 2009;37(9):2583–2589.
  19. 19 Bauer MP et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect. 2009;15: 1067-1079.


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