Timely guidelines, regularly updated: COVID-19, C. difficile, and beyond

Dear All,

During the 18-19 Nov 2019 FDA-IDSA-NIAID-Pew workshop on ways to enhance antibacterial research (link), we spent some time discussing the slow pace of updates to most guidelines. With the notable exception of the rapid guidance updates used in the HCV community (link), most guidelines are updated infrequently and each update feels like a Herculean effort. 

But, perhaps this is now about to change! As a first hint, I was heartened to note that IDSA announced a rapid COVID-19 guidance expert panel on 1 April 2020 (link) and we now have guidelines for treatment (link, 11 April) and prevention (link, 27 April), with a promise of a guideline soon to come on diagnostics.

But even better because of the potential for wider long-term impact, we have this pair of papers just out in Clinical Infectious Diseases:

  • Clancy, Buehrle, Vu, et al.: Impact of revised Infectious Diseases Society of America and Society for Healthcare Epidemiology of America clinical practice guidelines on the treatment of Clostridium difficile infections in the United States (link)
  • Gerding & Johnson: Guideline Recommendations: Optimal Timing of Publication and Resulting Rate of Adoption (link)

The paper by Clancy makes a very simple series of points:

  • A set of five (5!) randomized controlled trials (RCTs) published between 2000-2014 established clearly that oral vancomycin was superior to metronidazole for achieving initial and sustained resolution of symptoms due to C. difficile infection (CDI) .
  • Two RCTs published 2011-2012 showed that vancomycin and fidaxomicin were comparable for clinical cure of non-fulminant CDI, with fidaxomicin achieving superior sustained resolution of symptoms, in particular for infections caused by non-NAP1 strains.

But, these data did not begin to have an impact until 2014 … and it was not until publication of new CDI guidelines in 2018 that a strong impact was seen.

The timing of our collective shift in practice behavior is shown in the adjacent montage of 3 figures from the paper by Clancy et al. The x-axis is years from 2006-2020. The top panel is metronidazole use, the middle panel is vancomycin, and the bottom panel is fidaxomicin.

It’s really a very clear message: Change takes time and guidelines have a strong impact! 

And while it is great to (finally) see these new approaches being taken up based on guidelines, the 2018 CDI guidelines are already out of date (again!) in that they (i) do not consider bezlotoxumab, (ii) do not discuss recent safety alerts for fecal microbiota transplants (FMT), and (iii) do not analyze a new dosing regimen for fidaxomicin. 

So, how should we approach this challenge more consistently? We don’t want guidelines updated without careful consideration, but waiting a decade is too long … surely there’s a middle path! And, that’s where the editorial by Gerding and Johnson taken with the rapid COVID-19 process gives hope. Representing IDSA and SHEA, respectively, these two senior society representatives review the challenges of guideline updates and conclude that:

  • “IDSA and SHEA are both eager to keep guidelines updated and more current …
  • “… an updated IDSA/SHEA guideline committee has been formed that is focused only on potential new treatment recommendations …” and
  • “Failure to update CDI guidelines in a timely fashion in the past can be improved.”

I wholeheartedly concur! And I also hope that the experience with rapid COVID-19 guidelines can be transferred to all of the other valuable society guidelines. If we make it easier to update them, then the knowledge that updates will continue to be generated should reduce the pressure on any given update. As the saying goes, we should not allow the perfect to be the enemy of the merely good — let’s avoid paralysis by analysis!

All best wishes, –jr

PS: The newsletter on Movies to Discovery Antibiotics By provoked a lot interest and there are several new items added to the online version of the newsletter (link). Check it out: An excerpt from Osler! A movie featuring counterfeit penicillin! And, an opera!

PPS: Likewise, the list of papers on secondary infections with COVID-19 continues to grow — see the updates to that newsletter online (link).

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Operating Partner, Advent Life Sciences. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: https://amr.solutions/blog/. All opinions are my own.

Current funding opportunities:

  • Dates for the 2020 funding rounds for Novo REPAIR Impact Fund will be announced May 2020. Go here for current details.
  • 2020 funding rounds for CARB-X have not been announced.
  • The Global AMR R&D Hub’s dynamic dashboard (link) summarizes funders and projects by geography, stage, and more.

Upcoming meetings of interest to the AMR community:

  • 12 May 2020 (online, 17:00-18:30 CEST): GARDP REVIVE webinar. Title: “Probability of target attainment analyses for dose selection in antimicrobial drug development.” Speaker: Shampa Das. Go here to register.
  • 19 May 2020 (online, 17:00-18:30 CEST): GARDP REVIVE webinar. Title: “Assay development for measuring antibiotic accumulation in Gram-negative bacteria.” Speakers: Jessica Blair, Mark Bronstrop, David Six. Go here to register.
  • [NEW] 28 May 2020 (online, noon-1p EST): CARB-X webinar. Title: “How to Prepare for an FDA Pre-IND Meeting: Planning for Success.” Speakers: Carmella Moody and Michael Bevilacqua. Go here to register.
  • 9 Jun 2020 (online, 17:00-18:30 CEST): GARDP REVIVE webinar. Title: “Test tube to patient: PK/PD of fixed dose beta-lactam/beta-lactamase inhibitor combinations.” Speaker: Vincent Tam. Go here to register.
  • 30 Jun 2020 (online, 17:00-18:30 CEST): GARDP REVIVE webinar. Title: “Clinical development of antimicrobials – Phase 1 development challenges.” Speaker: Markus Zeitlinger. Go here to register.
  • 9 Jul 2020 (online, 09:00-10:30 CEST): GARDP REVIVE webinar. Title: “The challenges and opportunities for antimicrobial R&D in low- and middle-income countries – India case study.” Speaker: Anand Anandkumar and Kamini Walla. Go here to register.
  • 17 Jul-2 Aug 2020 (Marine Biology Laboratory, Woods Hole, MA): Residential course entitled “Molecular Mycology: Current Approaches to Fungal Pathogenesis.” This 2-week intensive training program has run annually for many years and gets outstanding reviews. Go here for details.
  • 29 Jul-2 Aug 2020 (Philadelphia, PA): Small World Initiative Instructor Training Workshop – training for undergraduate professors and high school teachers in wet lab techniques, parallel curricula, pedagogical instruction to engage students in the hunt to find new antibiotics in soil. Go here to register.
  • 4 Aug 2020 (Silver Spring): FDA workshop entitled “Development Considerations of Antifungal Drugs to Address Unmet Medical Need.” Go here to register.
  • 5 Aug 2020 (Silver Spring): FDA workshop entitled “Developing Antifungal Drugs for the Treatment of Coccidioidomycosis (Valley Fever) Infection.” Go here to register.
  • September 2020. University of Sheffield (UK). Applications are being taken for a new 1-year (full-time) or 2-year (part-time) Masters of Science course in Antimicrobial Resistance. The program runs annually from September and covers microbiology, clinical practice and policy. The course webpage is here.
  • 9-10 Sep 2020 (Washington, DC): US PACCARB public meeting. Go here for details.
  • 22-25 Sep 2020 (Albuquerque, New Mexico): Biannual meeting of the MSGERC (Mycoses Study Group Education and Research Consortium). Save-the-date announcement is here, details to follow.
  • 26-29 Oct 2020 (Rotterdam), Annual ESPID meeting (European Society for Pediatric ID, #38)
  • 10-13 Apr 2021 (Vienna): Annual ECCMID meeting (#31)
  • 20-24 June 2021 (Toronto): International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD-12). Go here for details.
  • 3-7 Jun 2021 (Anaheim), ASM Microbe 2021. Go here for details.
  • 8-11 Oct 2021 (Aberdeen, Scotland): 10th Trends in Medical Mycology. Go here for details.
  • 16-24 Oct 2021 (Annecy, France): Interdisciplinary Course on Antibiotics and Resistance (ICARe). This is a soup-to-nuts residential course on antibiotics, antibiotic resistance, and antibiotic R&D. The course is very intense, very detailed, and gets rave reviews. Registration is here and is limited to 40 students.


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