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

Evelina Tacconelli, Elena Carrara, Alessia Savoldi, Stephan Harbarth, Marc Mendelson, Dominique L Monnet, Céline Pulcini, Gunnar Kahlmeter, Jan Kluytmans, Yehuda Carmeli, Marc Ouellette, Kevin Outterson, Jean Patel, Marco Cavaleri, Edward M Cox, Chris R Houchens, M Lindsay Grayson, Paul Hansen, Nalini Singh, Ursula Theuretzbacher, Nicola Magrini, WHO Pathogens Priority List Working Group.

Lancet Infect Dis. 2018 Mar;18(3):318-327. doi: 10.1016/S1473-3099(17)30753-3. Epub 2017 Dec 21., 03/2018.

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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