As a member of the NICE committee that produced the latest treatment guidelines for Clostridioides difficile infection, I am often asked why fidaxomicin, the treatment with the strongest evidence for a sustained symptomatic cure, is not the first line option[i].
The NICE Managing Common Infections Committee does not routinely carry out health economic assessments of proposed choices of antimicrobials. But, given the high acquisition cost of fidaxomicin, the York Health Economic Consortium was asked to build an economic model to look at potential scenarios where fidaxomicin could be used first line. The model considered a range of benefits and harms including death as well as costs within the health service of recurrent infections.
Being involved in the development of the guidelines allowed me to reflect on what a big problem C. difficile was within secondary care in the early noughties. Often overshadowed by MRSA and certainly gaining less media attention infections peaked around the middle of the decade when over 45,000 cases were reported to England’s Health Protection Agency in 2006[ii]. Publications such as HPA’s ‘how to deal with the problem2’ set out clear guidelines and expectations for trusts with regards to infection control, testing and treatments. When fidaxomicin was first launched in 2012 the number of infections was already reducing but the introduction of a new class of antibiotic was exciting news to antibiotic stewards like myself who found ourselves running out of options once patients failed on repeated courses of vancomycin. However the cost was prohibitive and within my regional area, we were limited to using fidaxomicin as a third line treatment.
In 2012/13 a series of service evaluations in seven secondary care hospitals that slotted fidaxomicin into their C. difficile policies at different points showed that in hospitals where fidaxomicin was first line for all primary and recurrent episodes recurrence rates dropped significantly[iii]. However, when we looked at the evidence, together with the health economic model, it was very clear that by far the most cost-effective first-line option was vancomycin. Fidaxomicin would need to be around 30-50% of its current acquisition cost to be considered a cost-effective first line option.
Whilst the new guidelines will allow the use of fidaxomicin much earlier in the treatment pathway, where it undoubtedly has a place for some patients, within my current practice there is still a cost pressure associated with procurement of this antibiotic [NICE estimates around £5 million pa across England]. In a health system already under huge financial pressures, this will be significant.
Access to C. difficile treatments may also continue to be an issue – local health trusts are encouraged to explore how supply within primary care can be provided and to work with community pharmacies to carry adequate stock of oral vancomycin or fidaxomicin to avoid delays in starting treatment. Children and those not able to tolerate solid formulations may also struggle to administer treatment with fidaxomicin although oral granules will soon be launched[iv].
Looking to the future I am keen to see how things move forward with C. difficile treatments. If the cost of fidaxomicin is reduced to a level where cost-effectiveness may be achieved, will NICE relook at the current guideline? Is there an argument to centralise funding for fidaxomicin to avoid ‘postcode prescribing’? If safety concerns regarding faecal transplants diminish, will more patients and clinicians accept this as an option? What mitigations can be put into place in primary care to ensure patients have access to oral vancomycin and fidaxomicin as and when they need it?
I have been fortunate enough to work with two of our speakers over the last year on projects that they will be discussing during the webinar and I am looking forward to hearing their thoughts and opinions on this important and sometimes controversial topic.
Marisa will be exploring this topic in more detail at BSAC’s FREE Infections Clinical Dilemmas webinar on Gastrointestinal infections, taking place, 15 February 2022, 1630-1800hrs GMT, Registration open – register your FREE place now.
Marisa Lanzman is Senior Pharmacist at Microbiology & ITU, Royal Free London NHS Foundation Trust. She is a member of the NICE Managing Common Infections guidelines committee and the UKCPA Pharmacy Infection Network committee. Her interests include Antimicrobial Stewardship in secondary care with a focus on training standards for pharmacists and the management of sepsis.
[i] Clostridioides difficile infection: antimicrobial prescribing
NICE guideline Published: 23 July 2021 www.nice.org.uk/guidance/ng199
[ii] Clostridium difficile infection: How to deal with the problem DH and HPA Publication Date December 2008 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/340851/Clostridium_difficile_infection_how_to_deal_with_the_problem.pdf
[iii] 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. 2016;35(2):251-259. doi:10.1007/s10096-015-2538-z