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Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis

Evelina Tacconelli 1 Elena Carrara 1, 2 Alessia Savoldi 1 Stephan Harbarth 3 Marc Mendelson 4 Dominique Monnet 5 Céline Pulcini 6 Gunnar Kahlmeter 7 Jan Kluytmans 8 Yehuda Carmeli 9 Marc Ouellette 10 Kevin Outterson 11 Jean Patel 12 Marco Cavaleri 13 Edward Cox 14 Chris Houchens M Lindsay Grayson 15 Paul Hansen 16 Nalini Singh 17 Ursula Theuretzbacher 18 Nicola Magrini 19 Aaron Oladipo Aboderin Seif Salem Al-Abri Nordiah Awang Jalil Nur Benzonana Sanjay Bhattacharya Adrian John Brink Francesco Robert Burkert Otto Cars Giuseppe Cornaglia Oliver James Dyar Alex Friedrich Ana Gales Sumanth Gandra Christian Georg Giske Debra Goff Herman Goossens Thomas Gottlieb Manuel Guzman Blanco Waleria Hryniewicz Deepthi Kattula Timothy Jinks Souha Kanj Lawrence Kerr Marie-Paule Kieny Yang Soo Kim Roman Kozlov Jaime Labarca Ramanan Laxminarayan Karin Leder Leonard Leibovici Gabriel Levy-Hara Jasper Littman Surbhi Malhotra-Kumar Vikas Manchanda Lorenzo Moja Babacar Ndoye Angelo Pan David Paterson Mical Paul Haibo Qiu Pilar Ramon-Pardo Jesús Rodríguez-Baño Maurizio Sanguinetti Sharmila Sengupta Mike Sharland Massinissa Si-Mehand Lynn Silver Wonkeung Song Martin Steinbakk Jens Thomsen Guy Thwaites Jos Wm van der Meer Nguyen van Kinh Silvio Vega Maria Virginia Villegas Agnes Wechsler-Fördös Heiman Frank Louis Wertheim Evelyn Wesangula Neil Woodford Fidan Yilmaz Anna Zorzet
Abstract : Background: The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs. Methods: We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria. Findings: We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacterium's total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus. Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori, and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae, and Salmonella typhi were included in the high-priority tier. Interpretation: Future development strategies should focus on antibiotics that are active against multidrug-resistant tuberculosis and Gram-negative bacteria. The global strategy should include antibiotic-resistant bacteria responsible for community-acquired infections such as Salmonella spp, Campylobacter spp, N gonorrhoeae, and H pylori. Funding: World Health Organization.
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Submitted on : Tuesday, November 5, 2019 - 11:05:06 AM
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Evelina Tacconelli, Elena Carrara, Alessia Savoldi, Stephan Harbarth, Marc Mendelson, et al.. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. The Lancet Infectious Diseases, New York, NY : Elsevier Science ; The Lancet Pub. Group, 2001-, 2018, 18 (3), pp.318-327. ⟨10.1016/S1473-3099(17)30753-3⟩. ⟨hal-02347423⟩



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