Treating resistant Gram-negatives: IDSA provides pragmatic expert advice

Dear All,

IDSA (Infectious Diseases Society of America) have today released an eagerly awaited new guidance document on treating infections due to resistant Gram-negative bacteria (link).

8 Apr 2021 update: IDSA have published an updated version of this document. It excellent to see IDSA working steadily to provide up-to-the-minute advice!

24 Nov 2021 update: IDSA have maintained their concept of incremental edits to this guidance by releasing the next version of their guidance!

The thing that makes this document unusual is that it is an expert guidance rather than a formal guideline. Although there is value in formal guidelines that carefully review all data using a GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework, such guidelines take a long time to create and are only updated infrequently.

Based on a recognition that lack of timely guideline updates meant that inferior colistin-based regimens were being used reasonably commonly, a discussion of guidelines ensued during the 18-19 Nov 2019 FDA-IDSA-NIH-Pew Workshop on “Enhancing Antibacterial Trials In The US” (link to a newsletter on a report from Alan Carr showing continued use of colistin, link to a newsletter with yet more data on the toxicity of colistin, link to a newsletter about the 18-19 Nov meeting).

At that meeting, we concluded there was a need for a living guidance document that included the sort of thing that one peer would tell another about approaches to difficult situations. The idea was that the treating physician must respond to the situation at hand based on available knowledge and that having insights from such a document would be infinitely better than the haphazard data you might find if you went to the library and searched to find the available tidbits. 

So, we now have this first-ever guidance document from IDSA on treatment of resistant Gram-negatives. Authored by a well-respected group of authors (Tamma, Aitken, Bonomo, Mathers, van Duin, and Clancy) that includes both adult and pediatric specialists, the introduction makes clear the special character of this document:

  • “IDSA acknowledged that the ability to address rapidly evolving topics such as AMR was limited by prolonged timelines needed to generate new or updated clinical practice guidelines.
  • “As an alternative and complement to comprehensive clinical practice guidelines, IDSA endorsed developing more narrowly focused guidance documents for the treatment of specific infectious processes.
  • “Guidance documents will address specific clinical questions for difficult-to-manage infections that are not covered by present guidelines.
  • “The documents will be prepared by a small team of experts based on a comprehensive (but not necessarily systematic) review of the literature. Additionally, such guidance documents will not include a formal grading of the evidence, unlike IDSA guidelines, which utilize the GRADE framework.
  • “Over time, guidance documents may be transitioned to a GRADE format. Content will be disseminated on multiple platforms and updated as new data emerge.

So, this is exactly what we wanted … up-to-date advice from experts who have reviewed the known and then tackled the hard questions that arise about the unknown. The document takes a Q&A format and works serially through topics around ESBL-producing Enterobacterales, CRE, and DTR Pseudomonas aeruginosa (link to a newsletter about these acronyms; be sure to take time to refresh your understanding of the important new idea of DTR, Difficult-to-Treat Resistance). In the Q&A, I would draw your attention to Question 6 in the section on CRE:

  • Q: “What is the role of polymyxins for the treatment of infections caused by CRE?” 
  • A: “Polymyxin B and colistin should be avoided for the treatment of infections caused by CRE. Colistin can be considered as a last resort for uncomplicated CRE cystitis.”

With thanks to IDSA and the expert authors: Here’s to seeing this guidance improve outcomes for our patients by moving the community away from colistin in favor of better products!

All best wishes, –jr

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: All opinions are my own.

Current funding opportunities:

  • Novo REPAIR Impact Fund closed its most recent round on 31 Jul 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.
  • It’s not a funder, but AiCuris’ AiCubator offers incubator support to very early stage projects. Read more about it here.

Upcoming meetings of interest to the AMR community:

  • (it’s over now, but you can still watch it!) 24-28 Aug 2020 BEAM Alliance-sponsored AMR Conference. Go here to access the recorded sessions. This was a very, very good meeting! In particular, please note these two sessions from the final day … both are free on YouTube:
    • “Spotlight on UK | The Investor Action on AMR” (link). Chaired by Louise Norton-Smith (Head of Global AMR Strategy & Delivery, UK Dept of Health) with a key note by Dame Sally Davies (UK Special Envoy on AMR) in which we learn why we should #SaveTheLobster (see notes in this newsletter).
    • “The future of AMR – How a new post COVID19 policy roadmap could look like” (link). Chaired by Marc Gitzinger (CEO BioVersys and VP of BEAM Alliance, the core sponsor of the AMR Conference), this session has speakers from the Government of India (Renu Swarup), the UK (Dame Sally), FIND (a global non-profit focused on diagnostics), EU Parliament (Tiemo Woelken, MEP), and the US (Evan Loh, CEO Paratek and Chair of the Antimicrobial Working Group).
  • 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.
  • 10 Sep 2020 (online, 7-8.30a EST, noon-1.30p UK): Pfizer-sponsored global roundtable chaired by Dame Sally Davies entitled “The global antimicrobial crisis: Rethinking how we secure and value antibiotics for the future.” This was supposed to be a symposium at ECCMID 2020, but now it’s a webinar. Register here.
  • 24 Sep (online, 9-10.30a EST): “The global movement of microorganisms:  Tracking the spread of difficult-to-treat infections”, from a 4-part series sponsored by Wellcome Trust entitled “AMR in the Light of COVID-19 Webinar Series; From hypothetical to reality:  How COVID-19 foretells a world without antibiotics”. No registration link yet … watch for it in future newsletters or on meetings page of (link). For now, just mark your calendar. Really unfortunate overlap with the next meeting, but both are being recorded … you’ll have to pick one to attend live and the other for replay!
  • 24 Sep 2020 (online, 15.30-17.30 CEST; 9.30-11.30a EST; 7-9p IST): Antibiotic Bootcamp Series webinar entitled “Moving from preclinical to clinical-stage: Challenges and opportunities.” Moderated by Erin Duffy (CARB-X), this webinar is jointly sponsored by GARDP, CARB-X, Novo REPAIR, JPIAMR, Wellcome Trust, ASM, and ESCMID. Since we can’t the ASM-ESCMID meeting, we’re still going to have the bootcamps! Go here to register.
  • [NEW]  24 Sep 2020 (online, 17.15-18.15 CEST): ECCVID (ESCMID Conference on Coronavirus Disease) includes an AMR-focused symposium entitled “Antimicrobial resistance and COVID-19: learning policy lessons from one another” featuring Christine Ardal (Norway), Chantal Morel (Switzerland), and Kevin Outterson (US). You have to dig a bit in the online program to find this one, but it’s there! Go here to register.
  • 30 Sep 2020 (online, 2pm BST): Longitude Prize Sprint Workshop 2 entitled “Building Medtech Companies: Learn how to attract investment to fund product development and scale your company.” Details and registration are here.
  • 2 Oct 2020 (online meeting): 7th annual Boston Area Antimicrobial Research Network (BAARN) meeting. Go here for details.
  • 21-25 Oct 2020 (online meeting), IDWeek 2020. Go here for details.
  • 26-29 Oct 2020 (online meeting), Annual ESPID meeting (European Society for Pediatric ID, #38)
  • 27 Oct 2020 (online meeting), BARDA Industry Day, a discussion of U.S. Government medical countermeasure priorities. Mark your calendar now and watch this website for details.
  • 9-12 Jul 2021 (Vienna): Annual ECCMID meeting (#31)
  • 18-21 May 2021 (Albuquerque, New Mexico): Biannual meeting of the MSGERC (Mycoses Study Group Education and Research Consortium). Save-the-date announcement is here, details to follow.
  • 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.
  • 27 Jun-2 Jul 2021 (Ventura, CA): Gordon Research Conference entitled “Antimicrobial Peptides”. Go here for details, go here for the linked 26-27 Jun Gordon Research Seminar that precedes it.
  • 5-21 Aug 2021 (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.
  • 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.
  • 6-11 Mar 2022 (Il Ciocco, Tuscany): Gordon Research Conference entitled “New Antibacterial Discovery and Development”. Go here for details, go here for the linked 5-6 Mar Gordon Research Seminar that precedes it.


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