The World Health Organization (WHO) created the first Bacterial Priority Pathogens List (BPPL) in 2017 to identify antibiotic-resistant pathogens that are of the highest concern globally and to guide research and interventions. The WHO have recently updated their BPPL list due to the evolving landscape of antibiotic resistance and improved availability of surveillance data.
The WHO use the following criteria to determine the pathogens of greatest concern:
- Mortality
- Incidence (prevalence)
- Non-fatal health burden (morbidity)
- Trend of resistance
- Transmissibility
- Preventability in healthcare settings and community
- Treatability and pipeline (experimental drugs able to cover the bacteria).
The WHO have elevated several prominent drug-bug combinations in this update, including fluoroquinolone-resistant Salmonella typhi and third-generation cephalosporin-resistant Klebsiella pneumoniae. Carbapenem-resistant E. coli (CREC), Klebsiella pneumoniae (CRKP) and Acinetobacter baumannii (CRAB) remain in the Critical Group of pathogens and remain major concerns. Notably, carbapenem-resistant Pseudomonas aeruginosa (CRPA) has been demoted to the High Group due to relatively lower encountered rates of CRPA resistance.
Scientists at the IOI have been investigating rates of antibiotic resistance in pathogens that cause neonatal sepsis, in seven low- and middle- income countries (LMICs) as part of the BARNARDS study. Klebsiella pneumoniae was found to be the most common pathogen causing sepsis within the neonatal study, with resistance to multiple classes of antibiotics prevalent in samples. The decision to elevate carbapenem resistant K. pneumoniae to the top of the revised BPPL is consistent with our findings from our clinical studies in south Asia and Africa, as these cases leave clinicians with very few options for treatment. Moreover, we found high rates of K. pneumoniae resistant to third-generation cephalosporins across all countries. We believe that this should remain a high priority for global research.
There is currently a lack of data about the burden of AMR in LMICs (as identified in the GRAM report on AMR burden in 2019), meaning decisions about global priorities can be over-reliant on data from high-income countries. IOI’s Global Surveillance of AMR programme, which includes the BARNARDS study, aims to address these gaps, and to highlight issues related to AMR and antibiotic use worldwide.
Last line antibiotics, such as carbapenems, are sometimes unavailable in some of the countries where we work in BARNARDS. In instances where they are available, they are very expensive and unaffordable for most patients. Therefore, prioritising common pathogens with resistance to more accessible antibiotics, such as third-generation cephalosporins is of the utmost importance in these settings to ensure access to effective treatment and reduce use of last-line antibiotics.
To tackle this global public health challenge, scientists at the IOI are developing novel combination therapies to protect the efficacy of carbapenems with a focus on Enterobacterales like K. pneumoniae. Noticeably, our pre-clinical in-vivo efficacy models focus on eradicating CRKP and CREC.
In our combination therapy work, we can restore the activity of carbapenems against bacteria that cause infections such as sepsis by co-administering compounds that target the resistance mechanisms of bacteria. Metallo β-lactamases, which degrade near all β-lactam antibiotics, are a resistance mechanism of emerging concern in particular in South East Asia and many parts of Africa.
Tackling the threat of AMR requires a coordinated global approach. In September 2024, during the UN General Assembly in New York, leaders from governments, industry, financial institutions and scientific organisations will come together for a UN High-Level Meeting on AMR. This meeting offers a timely opportunity for global leaders to unite to overcome one of the biggest health challenges facing our society today.
It is essential for pharmaceutical companies, governments and researchers to come together to ensure equitable and sustainable access to antibiotics. The IOI is working with governments around the world to provide up-to-date evidence about the spread of AMR, and offer sustainable solutions to tackle this global threat.
