The rise of antibiotic-resistant bacteria has been a global health problem for many years, but despite this, there have been no major advances in the development of new antimicrobial agents to treat these pathogens. Due to its huge global impact, the problem of multi-drug resistant tuberculosis (MDR-TB) is of particular concern, with the WHO reporting on the need for dedicated campaigns and strong research into developing new anti-TB agents. They noted that no new classes of antibacterials have been developed aimed at Gram-negative bacteria since the introduction of the quinolones in 1962.

Responding to this problem, the WHO has produced a three-tired priority list (critical, high, medium) of antibiotic-resistant bacteria that require new effective treatments. The major role of this list is to prioritise funding and coordinate R&D for the discovery and development of new agents that will be effective against resistant pathogens.

The WHO based their list on a four-step process using a multi-criteria decision analysis tool. First, antibiotic-resistant bacteria were selected, and suitable criteria were identified to rate the importance of these pathogens. This was followed by a survey to gain expert rankings for these criteria, and then a score for each bacterium was based on their weighting by 70 international experts against each of the criteria.

Twenty bacterial species (with 25 patterns of acquired resistance) were assessed using the following ten criteria: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in both the community and the health-care settings, treatability and pipeline. Bacteria were prioritised based on 33rd percentile of the bacterium’s total scores from cut-off. Bacteria responsible for chronic infections such as MDR-TB could not be included in this exercise, and therefore an exercise that addresses specific criteria for longer durations of therapy and outcomes is required.

The four most important criteria for deciding R&D focus were deemed to be: treatability, mortality, health-care burden and 10-year resistance trend. Antibiotic-resistant Gram-negative bacteria rated the highest priority on these four criteria. Those deemed to be of critical concern were: carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, followed by 3rd-generation cephalosporin-resistant and carbapenem-resistant Enterobacteriaceae. Those of high concern were: vancomycin-resistant Enterococcus faecium, methicillin and vancomycin resistant S. aureus, clarithromycin-resistant H. pylori, fluoroquinolone-resistant Campylobacter spp. and Salmonella spp, third-generation cephalosporin and fluoroquinolone resistant Neisseria gonorrhea. The third group of medium concern were: penicillin non-susceptible S. pneumoniae, ampicillin-resistant H. influenzae and fluoroquinolone resistant Shigella spp.

The authors noted this list provides a focus on where R&D for new antimicrobials should be centered, but does not prioritise public health initiatives such as sanitation and vaccination. They concluded that future work is needed to improve treatment options for MDR-TB, Gram-negative bacteria, and pathogens responsible for community-acquired infections, and require increased political and international approaches.

PMID: 29276051

Lancet Infect Dis. 2017 Dec 21. pii: S1473-3099(17)30753-3. doi: 10.1016/S1473-3099(17)30753-3. [Epub ahead of print]

Source: https://www.ncbi.nlm.nih.gov/pubmed/29276051?dopt=Abstract