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. 2023 Oct 16;77(Suppl 4):S279-S287.
doi: 10.1093/cid/ciad475.

The Antibacterial Resistance Leadership Group: Scientific Advancements and Future Directions

Henry F Chambers  1 , Heather R Cross  2 , Maria Souli  2 , Scott R Evans  3 , Robin Patel  4 , Vance G Fowler  2   5 ; Antibacterial Resistance Leadership Group
Collaborators, Affiliations

The Antibacterial Resistance Leadership Group: Scientific Advancements and Future Directions

Henry F Chambers et al. Clin Infect Dis. .

Abstract

In this overview, we describe important contributions from the Antibacterial Resistance Leadership Group (ARLG) to patient care, clinical trials design, and mentorship while outlining future priorities. The ARLG research agenda is focused on 3 key areas: gram-positive infections, gram-negative infections, and diagnostics. The ARLG has developed an innovative approach to clinical trials design, the desirability of outcome ranking (DOOR), which uses an ordinal measure of global outcome to assess both benefits and harms. DOOR was initially applied to observational studies to determine optimal dosing of vancomycin for methicillin-resistant Staphylcococcus aureus bacteremia and the efficacy of ceftazidime-avibactam versus colistin for the treatment of carbapenem-resistant Enterobacterales infection. DOOR is being successfully applied to the analysis of interventional trials and, in collaboration with the US Food and Drug Administration (FDA), for use in registrational trials. In the area of diagnostics, the ARLG developed Master Protocol for Evaluating Multiple Infection Diagnostics (MASTERMIND), an innovative design that allows simultaneous testing of multiple diagnostic platforms in a single study. This approach will be used to compare molecular assays for the identification of fluoroquinolone-resistant Neisseria gonorrhoeae (MASTER GC) and to compare rapid diagnostic tests for bloodstream infections. The ARLG has initiated a first-in-kind randomized, double-blind, placebo-controlled trial in participants with cystic fibrosis who are chronically colonized with Pseudomonas aeruginosa to assess the pharmacokinetics and antimicrobial activity of bacteriophage therapy. Finally, an engaged and highly trained workforce is critical for continued and future success against antimicrobial drug resistance. Thus, the ARLG has developed a robust mentoring program targeted to each stage of research training to attract and retain investigators in the field of antimicrobial resistance research.

Keywords: antibacterial agents; antibacterial resistance; bacterial infections; clinical trials; diagnostics.

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Conflict of interest statement

Potential conflicts of interest. All authors report funding support from the ARLG of the NIH and the National Institute of Allergy and Infectious Diseases (NIAID; UM1AI104681). H. R. C. and M.S. report salary support from the ARLG via Duke University (NIAID; UM1AI104681). H. F. C. reports royalties from the Sanford Guide to Antimicrobial Therapy; payment for expert testimony from Nexus Pharmaceuticals; participation on a Merck data and safety monitoring board for molnupiravir; and stock ownership in Moderna and Merck. S. R. E. reports grants from the NIAID, NIH, and Degruter (editor-in-chief for Statistical Communications in Infectious Diseases); royalties from Taylor & Francis; consulting fees from Genentech, AstraZeneca, Takeda, Microbiotix, Johnson & Johnson, Endologix, ChemoCentryx, Becton Dickinson, Atricure, Roviant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute, and SVB Leerink; payments from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); meeting support from the US Food and Drug Administration, Deming Conference on Applied Statistics, Clinical Trial Transformation Initiative, Council for International Organizations of Medical Sciences, International Chinese Statistical Association Applied Statistics Symposium, and Antimicrobial Resistance and Stewardship Conference; and board member participation for the NIH, Breast International Group, University of Pennsylvania, Duke University, Roche, Pfizer, Takeda, Akouos, Apellis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, AbbVie, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Advantagene, American Statistical Association, Society for Clinical Trials, and Frontier Science Foundation. R. P. reports grants or contracts from ContraFect, TenNor Therapeutics Limited, BIOFIRE, and Adaptive Phage Therapeutics; a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics through the Mayo Clinic; consulting fees from PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, HealthTrackRx, Netflix, Abbott Laboratories, Trellis Bioscience, Inc, Oxford Nanopore Technologies, and CARB-X; honoraria from the NBME, Up-to-Date, and the Infectious Diseases Board Review Course; a patent on Bordetella pertussis/parapertussis polymerase chain reaction issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an antibiofilm substance issued; and a financial relationship with Pathogenomix through the Mayo Clinic. V. G. F. reports personal consulting fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co, MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, Roche, and Pfizer (paid to author); grants from the NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from the Infectious Diseases Society of America for his service as associate editor of Clinical Infectious Diseases; travel support from Contrafect to 2019 European Congress of Clinical Microbiology and Infectious Diseases; and a sepsis diagnostics patent pending. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Evolution of the ARLG since inception. See Table 1 and text for names and brief descriptions of trials. Abbreviations: AR, antibacterial resistance; ARLG, Antibacterial Resistance Leadership Group; caz-avi, ceftazidime-avibactam; FDA, US Food and Drug Administration; GC, Gonorrhea-Chlamydia; IND, investigational new drug application; IDE, investigational device exemption; MDRO, multidrug-resistant organism; PRIMERS, platforms for rapid identification of MDR-gram-negative bacteria and evaluation of resistance studies; VENOUS, vancomycin-resistant enterococcal BSI outcomes study.
See this image and copyright information in PMC

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