Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis - 23/02/18

Doi : 10.1016/S1473-3099(17)30753-3

Evelina Tacconelli, ProfMD ^a,^b,^⁎ , Elena Carrara, MD ^a,^b,^{^{*
Contributed equally}}, Alessia Savoldi, MD ^a,^{^{*
Contributed equally}}, Stephan Harbarth, ProfMD ^c, Marc Mendelson, ProfMD ^d, Dominique L Monnet, PhD ^e, Céline Pulcini, ProfMD ^f, Gunnar Kahlmeter, ProfMD ^g, Jan Kluytmans, ProfMD ^h,ⁱ, Yehuda Carmeli, ProfMD ^j, Marc Ouellette, ProfMD ^k, Kevin Outterson, ProfJD ^l, Jean Patel, PhD ^m, Marco Cavaleri, PhD ⁿ, Edward M Cox, MD ^o, Chris R Houchens, PhD ^p, M Lindsay Grayson, ProfMD ^q, Paul Hansen, ProfPhD ^r, Nalini Singh, ProfMD ^s, Ursula Theuretzbacher, PhD ^t, Nicola Magrini, MD ^u
and the
WHO Pathogens Priority List Working Group^{^†}
Members shown at end of paper

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 W Friedrich, Ana C Gales, Sumanth Gandra, Christian Georg Giske, Debra A Goff, Herman Goossens, Thomas Gottlieb, Manuel Guzman Blanco, Waleria Hryniewicz, Deepthi Kattula, Timothy Jinks, Souha S Kanj, Lawrence Kerr, Marie-Paule Kieny, Yang Soo Kim, Roman S 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 L Paterson, Mical Paul, Haibo Qiu, Pilar Ramon-Pardo, Jesús Rodríguez-Baño, Maurizio Sanguinetti, Sharmila Sengupta, Mike Sharland, Massinissa Si-Mehand, Lynn L Silver, Wonkeung Song, Martin Steinbakk, Jens Thomsen, Guy E 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 O Yilmaz, Anna Zorzet

^a German Centre for Infection Research, Tübingen University Hospital, Tübingen, Germany

^b Verona University Hospital, Verona, Italy

^c World Health Organization Collaborating Centre on Patient Safety, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland

^d Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa

^e European Centre for Disease Prevention and Control, Stockholm, Sweden

^f EA 4360 APEMAC, Nancy University Hospital, Lorraine University, Nancy, France

^g Central Hospital, Växjö, Sweden

^h University Medical Center, Utrecht, Netherlands

ⁱ Amphia Hospital, Breda, Netherlands

^j Laboratory for Microbiology and Infection Control, Tel Aviv University, Tel Aviv, Israel

^k Laval University and Canadian Institutes for Health Research, Québec, QC, Canada

^l Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator CARB-X, Boston University, Boston, MA, USA

^m Centers for Disease Control and Prevention, Atlanta, GA, USA

ⁿ European Medicines Agency, London, UK

^o US Food and Drug Administration, Washington, DC, USA

^p Antibacterials Program Biomedical Advanced Research and Development Authority, Washington, DC, USA

^q Austin Health, University of Melbourne, Melbourne, VIC, Australia

^r Department of Infectious Diseases and Microbiology, University of Otago, Dunedin, New Zealand

^s Children’s National Health System, George Washington University, Washington, DC, USA

^t Center for Anti-infective Agents, Vienna, Austria

^u Essential Medicines and Health Products, World Health Organization, Geneva, Switzerland

^* Correspondence to: Prof Evelina Tacconelli, Infectious Diseases, Internal Medicine 1, Tübingen University Hospital, Tübingen 72074, Germany Correspondence to: Prof Evelina Tacconelli, Infectious Diseases Internal Medicine 1 Tübingen University Hospital Tübingen 72074 Germany

Summary

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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Plan

Introduction

Methods

Study design

Selection of antibiotic-resistant bacteria and criteria for the prioritisation of antibiotic-resistant bacteria

Evidence extraction and data synthesis

Expert rating of antibiotic-resistant bacteria and weighting of criteria to assess priority

Ranking stability assessment

Role of the funding source

Results

Discussion

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Vol 18 - N° 3

P. 318-327 - mars 2018 Retour au numéro

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Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis - 23/02/18

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