Analysis of the clinical pipeline of treatments for drug resistant bacterial infections: despite progress, more action is needed

Article Article scientifique Revue de la littérature Analysis of the clinical pipeline of treatments for drug resistant bacterial infections: despite progress, more action is needed eng 2022-01-10 2022-03-15 author Butler Mark S 0000-0001-6689-4236 author Gigante Valeria author Sati Hatim author Pastore Pauline 718927 author Al-Sulaiman Laila author Rex John H author Fernandes Prabhavathi author Arias Cesar A author Paul Mical author Thwaites Guy E author Czaplewski Lloyd author Alm Richard A 0000-0002-5056-7377 author Lienhardt Christian author Spigelman Melvin author Silver Lynn L author Ohmagari Norio author Kozlov Roman author Harbarth Stéphan Juergen 0000-0002-3551-1025 93885 author Beyer Peter 120544 e0199121 10.1128/AAC.01991-21 35007139 0066-4804 There is an urgent global need for new strategies and drugs to control and treat multidrug-resistant bacterial infections. In 2017, the World Health Organization (WHO) released a list of 12 antibiotic-resistant priority pathogens and began to critically analyze the antibacterial clinical pipeline. This review analyzes "traditional" and "nontraditional" antibacterial agents and modulators in clinical development current on 30 June 2021 with activity against the WHO priority pathogens mycobacteria and Clostridioides difficile. Since 2017, 12 new antibacterial drugs have been approved globally, but only vaborbactam belongs to a new antibacterial class. Also innovative is the cephalosporin derivative cefiderocol, which incorporates an iron-chelating siderophore that facilitates Gram-negative bacteria cell entry. Overall, there were 76 antibacterial agents in clinical development (45 traditional and 31 nontraditional), with 28 in phase 1, 32 in phase 2, 12 in phase 3, and 4 under regulatory evaluation. Forty-one out of 76 (54%) targeted WHO priority pathogens, 16 (21%) were against mycobacteria, 15 (20%) were against C. difficile, and 4 (5%) were nontraditional agents with broad-spectrum effects. Nineteen of the 76 antibacterial agents have new pharmacophores, and 4 of these have new modes of actions not previously exploited by marketed antibacterial drugs. Despite there being 76 antibacterial clinical candidates, this analysis indicated that there were still relatively few clinically differentiated antibacterial agents in late-stage clinical development, especially against critical-priority pathogens. We believe that future antibacterial research and development (R&D) should focus on the development of innovative and clinically differentiated candidates that have clear and feasible progression pathways to the market. Clostridioides difficile WHO priority pathogens Antibacterial pipeline Antibiotic Clinical trials Mycobacteria Nontraditional Traditional Tuberculosis. Dewey 616 World Health Organization 001 International 56 Département de médecine 221 false 526 Résistance aux antibiotiques 866 Antimicrobial agents and chemotherapy 66 3 08f6504b-68e7-4a9f-88b1-988c8fe62819 Article (Published version) Public aac.01991-21.pdf 3515793 application/pdf CC BY-4.0 Restricted 2022-07-11 2ce98b9f-b1f0-4e39-941d-afa029c9b4e8 Article (Accepted version) Public AAC.01991-21.pdf 1825169 application/pdf CC BY c393ed65-ac1e-4498-8e29-fedfd74972b0 Supplemental data Public aac.01991-21-s0001.pdf 222172 application/pdf Restricted 2022-09-16 openAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Analysis of the clinical pipeline of treatments for drug resistant bacterial infections: despite progress, more action is needed	Antimicrobial agents and chemotherapy			2022	129	215

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Pastore, Pauline