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

WHO Pathogens Priority List Working Group

Research output: Contribution to journalArticlepeer-review

1274 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)318-327
Number of pages10
JournalThe Lancet Infectious Diseases
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 2018

Bibliographical note

Funding Information:
Acknowledgments, We thank Anne McDonough for editorial support., WHO Pathogens Priority List working group, Aaron O Aboderin (Nigeria), Seif S Al-Abri (Oman), Nordiah Awang Jalil (Malaysia), Nur Benzonana (Turkey), Sanjay Bhattacharya (India), Adrian John Brink (South Africa), Francesco Robert Burkert (Germany), Otto Cars (Sweden), Giuseppe Cornaglia (Italy), Oliver James Dyar (Sweden), Alexander W Friedrich (Netherlands), Ana C Gales (Brazil), Sumanth Gandra (India), Christian G Giske (Sweden), Debra A Goff (USA), Herman Goossens (Belgium), Thomas Gottlieb (Australia), Manuel Guzman Blanco (Venezuela), Waleria Hryniewicz (Poland), Deepthi Kattula (India), Timothy Jinks (UK), Souha S Kanj (Lebanon), Lawrence Kerr (USA), Marie-Paule Kieny (WHO), Yang Soo Kim (South Korea), Roman S Kozlov (Russia), Jaime Labarca (Chile), Ramanan Laxminarayan (USA), Karin Leder (Australia), Leonard Leibovici (Israel), Gabriel Levy Hara (Argentina), Jasper Littman (Germany), Surbhi Malothra-Kumar (Belgium), Vikas Manchanda (India), Lorenzo Moja (WHO), Babacar Ndoye (Senegal), Angelo Pan (Italy), David Paterson (Australia), Mical Paul (Israel), Haibo Qiu (China), Pilar Ramon-Pardo (USA), Jes?s Rodr?guez-Ba?o (Spain), Maurizio Sanguinetti (Italy), Sharmila Sengupta (India), Mike Sharland (UK), Massinissa Si-Mehand (WHO), Lynn L Silver (USA), Wonkeung Song (South Korea), Martin Steinbakk (Norway), Jens Thomsen (United Arab Emirates), Guy E Thwaites (UK), Jos van der Meer (Netherlands), Nguyen Van Kinh (Vietnam), Silvio Vega (Panama), Maria Virginia Villegas (Colombia), Agnes Wechsler-F?rd?s (Austria), Heiman F L Wertheim (Netherlands), Evelyn Wesangula (Kenya), Neil Woodford (UK), Fidan O Yilmaz (Azerbaijan), Anna Zorzet (Sweden)., Disclaimer, The authors alone are responsible for the views expressed in this Article and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated.

Funding Information:
For all experts, advice was provided in their personal capacity. The views in this report do not necessarily reflect, and should not be interpreted as, the official position of any agency or institution. ET reports research grants from Innovative Medicines Initiative (IMI) Brussels and Deutsches Zentrum für Infektionsforschung. SH reports research grants from IMI Brussels, grants from Pfizer, and personal fees from Novartis, DNA Electronics, Bayer, and GlaxoSmithKline. CP reports grants from IMI Brussels, and personal fees from Pfizer. YC reports grants from Merck Sharp & Dohme, AstraZeneca, Allecra Therapeutics, and Shionogi, and personal fees from Merck Sharp & Dohme, AstraZeneca, DaVoltera, Intercell AG, Allecra Therapeutics, BioMerieux SA, Rempex Pharmaceuticals, Nariva, Achoagen, Roche, and Pfizer. KO reports grants from Biomedical Advanced Research and Development Authority and Wellcome Trust. PH co-owns the 1000Minds decision-making software, which is freely available for academic use. UT reports research grants from IMI Brussels. All other authors declare no competing interests.

Publisher Copyright:
© 2018 Elsevier Ltd

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