Dear All,
A recent paper by Hasegawa et al. and a multi-paper supplement, both in Clinical Infectious Diseases, combine to provide an interesting message.
First, the paper by Hasegawa and colleagues. I’ve taken the title of this newsletter from an accompanying editorial by MacDougall who opens his commentary with “If there is one thing infectious diseases clinicians seem to agree on, it is the value of incorporating local antimicrobial susceptibility data into the antimicrobial prescribing process.”
For those not familiar with them, an antibiogram is simply a tabular summary of the susceptibility (or not) of recently tested organisms from your clinical care setting. The value of using local susceptibility to guide empirical therapy is something that is recommended by countless guidelines. Recognizing that the accuracy of antibiograms had only occasionally been assessed, these authors set out to leverage the availability of modern electronic datasets to put antibiograms to the test.
Based on data on 1.5 million isolates from 127 VA hospitals for the period 2010-2019, the author conclude that systematically constructed antibiograms for Klebsiella and E. coli would have predicted resistance with an accuracy only slight better than a coin toss (technically, AUCs on receiver-operator curves were generally < 0.7 for predicting resistance to ceftriaxone, fluoroquinolones, and trimethoprim-sulfa). Although there are some limitations to the study, the authors conclude that antibiograms are unlikely to ever achieve high predictivity when used as the sole prediction tool.
In parallel, I was fascinated by papers in the July 2023 CID supplement entitled “The Evolving Challenges of Antibiotic Resistance in Low- and Middle-Income Countries: Priorities and Solutions.” The papers in the supplement span everything from the impact of COVID on antibiotic use to the CDC’s multi-country ARCH (Antibiotic Resistance in Communities and Hospitals) project to track resistant bacteria in humans in multiple low- and middle-income countries by assessing colonization in (mostly) healthy people. The supplement was supported by CDC’s Global Antimicrobial Resistance Laboratory and Response Network. Even if surveillance is not your specific area of interest, a read of the overview paper and a scan of the table of contents are worth your time. And for those interested in surveillance, the 7 further ARCH-related papers in the supplement discuss data from Chile, Guatemala, Botswana, Kenya, South India, and Bangladesh — happy reading!
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So, what’s the connection? Well, antibiograms are necessarily based on susceptibility testing of isolates submitted for testing — and that generally means isolates taken from someone who is ill. Thus, at least one weakness of antibiograms is that they will tend to overestimate resistance in healthy people.
A better approach to gaining local knowledge of susceptibility would be to have data from the community as well as the healthcare setting (and also children vs. adults, if possible). And, that’s precisely the idea of the ARCH studies in the CID supplement. The overview paper on CDC’s ARCH by Styczynski et al. pulls it all together for you in its very title: “Using Colonization to Understand the Burden of Antimicrobial Resistance Across Low- and Middle-Income Countries.” Although relatively intensive to conduct, these are the type of data that could inform a better empirical guess.
Well done to all these authors and to the CDC for taking an innovative view to data collection! As Styczynski & colleagues conclude, “…incorporating estimates of colonization into existing global efforts to surveil for AMR, such as those spearheaded by the World Health Organization Global Antimicrobial Resistance and Use Surveillance System, could provide support for routine evaluation of colonization as a metric by which to measure AMR burden and emergence.”
22 Aug 2023 addendum: As a build on this, it was pointed out to me (thank you, Antoine Andremont!) that WHO’s GLASS has a project called “Tricycle” in which the rate of ESBL-E. coli is used as a common indicator human samples, poultry and water bodies – specifically sewage, market runoff and river sites in urban areas. The connection to ARCH is that Tricycle suggests that community-based screening be done by collecting stool samples from pregnant women at delivery. Clever!
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: https://amr.solutions/blog/. All opinions are my own.
Current funding opportunities (most current list is here)
- The AMR Industry Alliance has announced that applications are again open for its annual Stewardship Prize. The Alliance began the Stewardship Prize in 2021 to identify and support innovative approaches to combatting antimicrobial resistance in low-to-moderate-income countries — the winning application receives CHF 10,000. Applications close September 1, 2023; go here to see past winners and here to apply.
- The AMR Action Fund is now open to proposals for funding of Phase 2 / Phase 3 antibacterial therapeutics. Per its charter, the fund prioritizes investment in treatments that address a pathogen prioritized by the WHO, the CDC and/or other public health entities that: (i) are novel (e.g., absence of known cross-resistance, novel targets, new chemical classes, or new mechanisms of action); and/or (ii) have significant differentiated clinical utility (e.g., differentiated innovation that provides clinical value versus standard of care to prescribers and patients, such as safety/tolerability, oral formulation, different spectrum of activity); and (iii) reduce patient mortality. It is also expected that such agents would have the potential to strongly address the likely requirements for delinked Pull incentives such as the UK (NHS England) subscription pilot and the PASTEUR Act in the US. Submit queries to contact@amractionfund.com.
- BARDA’s long-running BAA-18-100-SOL-00003 offers support for both antibacterial and antifungal agents. This BAA has offered 4 deadlines/year since 2018 … check the most current amendment for details.
- INCATE (Incubator for Antibacterial Therapies in Europe) is an early-stage funding vehicle supporting innovation vs. drug-resistant bacterial infections. The fund provides advice, community, and non-dilutive funding (€10k in Stage I and up to €250k in Stage II) to support early-stage ventures in creating the evidence and building the team needed to get next-level funding. Details and contacts on their website (https://www.incate.net/).
- These things aren’t sources of funds but would help you develop funding applications
- AiCuris’ AiCubator offers incubator support to very early stage projects. Read more about it here.
- The Global AMR R&D Hub’s dynamic dashboard (link) summarizes the global clinical development pipeline, incentives for AMR R&D, and investors/investments in AMR R&D.
- Diagnostic developers would find valuable guidance in this 6-part series on in vitro diagnostic (IVD) development. Sponsored by CARB-X, C-CAMP, and FIND, it pulls together real-life insights into a succinct set of tutorials.
- In addition to the lists provided by the Global AMR R&D Hub, you might also be interested in my most current lists of R&D incentives (link) and priority pathogens (link).
Upcoming meetings of interest to the AMR community (most current list is here):
- [NEW and especially recommended for anyone who would like a good introduction to the AMR problem] 24 Aug 2023 (online, 6.45am EST, 12.45p CET, 4.15p India): Webinar entitled “Small and Medium Scale Antibiotic Developers, Challenges they face and the way forward.” Sponsored by the India-based CSE (Centre for Science and Environment, an NG based in New Delhi), this is the 2nd in a 3-part webinar series — go here to register. The first webinar on “The Crisis in Antibiotic R&D” can be seen on YouTube and was an excellent 90-minute tour of the general AMR problem on 28 July 2023. The webinar was held in conjunction with release of a report entitled “A Developing Crisis” by CSE, was hosted by Sunita Narain (Director General of CSE and a member of the Global Leaders Group on AMR), and featured a global roster of speakers from India, Europe, and United States. A 3rd webinar on solutions is planned.
- [NEW] 29 Aug 2023 (online, 1-2p EST): Webinar entitled “Preparedness to Combat Infectious Disease and Drug-Resistant Bacterial Threats.” Sponsored by the Duke-Margolis Center for Health Policy, the webinar will focus on preparedness in the context of both viral and bacterial threats, including drug-resistant bacteria and antimicrobial resistance (AMR). Duke-Margolis webinars are hosted by Mark McClellan (founding Director of the D-M Center and formerly Commissioner of the US FDA) and are always good value. Go here for the full agenda and to register.
- 19-22 Sep 2023 (Boston, USA): ASM-ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. This is an excellent development focused meeting … highly recommended! Go here for details and to register.
- 7-15 Oct 2023 (residential, Annecy, France): ICARe, the Interdisciplinary Course on Antibiotics and Resistance. Now in its 7th year, this course is a deep-dive into the world of antibiotic development. Intense, rigorous, and HIGHLY recommended. Seats are always limited … apply sooner rather than later! Go here for details.
- 11-15 Oct 2023 (Boston, USA): IDWeek 2023, the annual meeting of the Infectious Diseases Society of America. Go here for details and to register.
- 20-23 Oct 2023 (Athens, Greece): 11th TIMM (Trends in Medical Mycology). Go here for details.
- 6-7 Feb 2024 (online): Antimicrobial Chemotherapy Conference. This is an annual, free of charge conference that is co-organized by GARDP and the British Society for Antimicrobial Chemotherapy (BSAC). Details to follow — for now, just mark your calendar.
- 27-30 April 2024 (Barcelona, Spain): 34th ECCMID, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. Go here for details.
- [NEW] 26-31 May 2024 (Montreal, Canada): EDAR7, the McGill AMR Centre’s 7th edition of their Environmental Dimension of Antimicrobial Resistance conference. Go here for details; final abstract deadline is 21 Dec 2023.
