WHO Updates Bacterial Priority Pathogens List for Antimicrobial Resistance in 2024
The World Health Organization (WHO) has recently updated its Bacterial Priority Pathogens List (BPPL) for 2024, a document that prioritizes 15 families of antibiotic-resistant bacteria. These pathogens are grouped into critical, high, and medium-priority categories to guide the development of new treatments and curb the spread of antimicrobial resistance (AMR).
Understanding Antimicrobial Resistance
Antimicrobial resistance (AMR) occurs when bacteria, viruses, fungi, and parasites evolve to withstand the effects of medications designed to kill them. These "superbugs" are a growing public health threat, fueled by the misuse and overuse of antimicrobials in humans, animals, and agriculture. As resistance develops, these medications become less effective, making infections harder to treat and increasing the risk of serious illness and death. As a result, the WHO has declared that AMR is one of the top 10 global public health threats facing humanity [1].
Among the various types of antimicrobial resistance, antibiotic resistance in bacteria is particularly urgent. Over the past several decades, bacteria causing common or severe infections have developed resistance to every new antibiotic introduced to the market. Specifically, gram-negative bacteria are notorious for their ability to develop multiple resistance mechanisms and transmit them to other bacteria [2].
The 2017 Bacterial Priority Pathogen List
Recognizing the gravity of the AMR crisis, the WHO has long advocated for a coordinated global effort to contain and mitigate the impact of antimicrobial resistance. In 2017, the WHO released its Bacterial Priority Pathogen List (BPPL), which highlighted 12 families of bacteria that pose the greatest threat to human health due to their resistance to existing treatments. This list was created to guide and promote research and development of new antibiotics, forming a crucial part of WHO’s strategy to combat the growing global resistance to antimicrobial medicines.
The BPPL is divided into three categories based on the urgency of the need for new antibiotics: critical, high, and medium priority. The critical group comprises multidrug-resistant bacteria that pose the highest threat, especially in healthcare settings. The high and medium-priority groups include other increasingly drug-resistant bacteria that cause common diseases such as gonorrhea and food poisoning.
Tuberculosis, despite its growing resistance to traditional treatments, was not included in the BPPL because it is targeted by other dedicated programs. Other bacteria, such as Streptococcus A and B and Chlamydia, were also not included due to their low levels of resistance to current treatments and their relatively lower threat to public health.
The criteria for selecting bacteria included the lethality of the infections they cause, the duration of hospital stays required for treatment, the frequency of resistance to existing antibiotics, the ease of transmission, the potential for prevention through hygiene and vaccination, the availability of treatment options, and the status of new antibiotics in the R&D pipeline.
The BPPL isn't just a list for the WHO; it's a call to action for governments and the scientific community. It aims to incentivize policies that promote both basic science and advanced R&D, encouraging participation from both public and private sectors. The list seeks to steer new initiatives like the WHO/DNDi Global Antibiotic R&D Partnership, which emphasizes the not-for-profit development of new antibiotics.
Critical priority
The most critical group on the list includes multidrug-resistant bacteria that present severe threats in hospitals, nursing homes, and among patients requiring medical devices like ventilators and blood catheters. These bacteria can cause severe and often fatal infections like bloodstream infections and pneumonia, and have become resistant to carbapenems and third-generation cephalosporins, which are among the best available treatments for multidrug-resistant infections.
Acinetobacter baumannii, carbapenem-resistant
Pseudomonas aeruginosa, carbapenem-resistant
Enterobacteriaceae, carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-producing
High priority
Enterococcus faecium, vancomycin-resistant
Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant
Helicobacter pylori, clarithromycin-resistant
Campylobacter spp., fluoroquinolone-resistant
Salmonellae, fluoroquinolone-resistant
Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant
Medium priority
Streptococcus pneumoniae, penicillin-non-susceptible
Haemophilus influenzae, ampicillin-resistant
Shigella spp., fluoroquinolone-resistant
The 2024 Bacterial Priority Pathogen List
The updated 2024 BPPL builds on the 2017 list, incorporating the latest evidence and expert insights. It continues to categorize pathogens based on their threat level—critical, high, and medium—reflecting their impact on global health and the urgency of developing new treatments. The updated list addresses some limitations of the initial list and reflects a more comprehensive understanding of the evolution and burden of drug-resistant bacterial pathogens.
Critical priority
Acinetobacter baumannii, carbapenem-resistant
Enterobacterales, third-generation cephalosporin-resistant
Enterobacterales, carbapenem-resistant
Mycobacterium tuberculosis, rifampicin-resistant
High priority
Salmonella Typhi, fluoroquinolone-resistant
Shigella spp., fluoroquinolone-resistant
Enterococcus faecium, vancomycin-resistant
Pseudomonas aeruginosa, carbapenem-resistant
Non-typhoidal Salmonella, fluoroquinolone-resistant
Neisseria gonorrhoeae, third-generation cephalosporin- and/or fluoroquinolone-resistant
Staphylococcus aureus, methicillin-resistant
Medium priority
Group A streptococci, macrolide-resistant
Streptococcus pneumoniae, macrolide-resistant
Haemophilus influenzae, ampicillin-resistant
Group B streptococci, penicillin-resistant
Key Changes from 2017 to 2024
The 2024 update reflects the dynamic nature of AMR. Five pathogen-antibiotic combinations were removed, and four new combinations were added. Notably, third-generation cephalosporin-resistant Enterobacterales (3GCRE) now appear as a standalone item in the critical category, emphasizing their significant burden. The rise of 3GCRE in neonatal sepsis, particularly in low- and middle-income countries (LMICs), has been associated with increased morbidity and mortality [3].
Additionally, rifampicin-resistant tuberculosis (RR-TB) was added to the critical priority group due to its significant challenges in diagnosis and treatment, as well as its high mortality rate. The updated list also moved carbapenem-resistant Pseudomonas aeruginosa from critical to high priority, reflecting a lower transmission capability compared to other carbapenem-resistant organisms and a decrease in resistance in at least one WHO region [3].
Emphasizing Community Pathogens
The updated BPPL recognizes the growing threat of community pathogens. Fluoroquinolone-resistant Shigella, previously in the medium-priority group, has moved to high priority due to its global impact on diarrheal mortality. This impact is particularly apparent among children in developing countries and men who have sex with men in urban areas of high-income countries [3].
Fluoroquinolone-resistant Salmonella Typhi and non-typhoidal Salmonella have also been elevated in priority in the updated BPPL, although they remain in the high-priority group. Salmonella Typhi, the leading cause of typhoid fever, is responsible for approximately 10 million cases and 116,800 deaths annually and is already resistant to several antibiotics. Although non-typhoidal Salmonella is distinct from Salmonella Typhi, it **can indirectly increase resistance in typhoidal Salmonella through the transfer of resistance genes [3].
New Additions and Removals
New drug-bug combinations in the 2024 BPPL include macrolide-resistant group A streptococci, penicillin-resistant group B streptococci, and macrolide-resistant Streptococcus pneumoniae, in the medium-priority group. These pathogens are of particular concern due to their high disease burden in pediatric and elderly populations in low and middle-income countries [3].
Removals from the BPPL include clarithromycin-resistant Helicobacter pylori, fluoroquinolone-resistant Campylobacter spp., penicillin-non-susceptible Streptococcus pneumoniae, third-generation cephalosporin-resistant Providencia spp., and vancomycin-intermediate and -resistant Staphylococcus aureus due to recent reports of decreases in global resistance [3].
The Need for Global Surveillance of AMR
Global surveillance of AMR involves systematically collecting, analyzing, and interpreting data on the prevalence and trends of resistant pathogens. This data is crucial for identifying hotspots and trends in AMR, which enables targeted interventions and resource allocation. By understanding where and in which populations AMR is most prevalent, healthcare providers can tailor their treatment protocols to the specific resistance patterns they are likely to encounter.
Moreover, surveillance data is invaluable for monitoring the effectiveness of public health interventions. By tracking changes in resistance patterns over time, policymakers can assess whether their strategies are working and make necessary adjustments. This feedback loop is essential for developing dynamic and responsive public health policies that can adapt to the evolving threat of AMR.
The global nature of AMR necessitates a coordinated international response. Resistant pathogens can easily spread across borders through travel, trade, and migration, making it a global issue that requires global solutions. The World Health Organization (WHO) has been instrumental in promoting and facilitating global AMR surveillance through initiatives like the Global Antimicrobial Resistance and Use Surveillance System (GLASS). Endorsed by the Sixty-eighth World Health Assembly, GLASS supports GAP-AMR’s objective to strengthen knowledge through surveillance and research, continuously filling knowledge gaps to inform strategies at all levels.
Despite the clear need for global AMR surveillance, several challenges remain. Data gaps are a significant issue, particularly in low- and middle-income countries that often lack the infrastructure and resources for comprehensive surveillance. This leads to an incomplete global picture of AMR patterns. Standardizing methodologies and reporting standards across different countries is also challenging but necessary for meaningful data comparison and compilation. Additionally, sustaining AMR surveillance efforts requires substantial financial and human resources, which can be difficult to secure in the face of competing public health priorities.
However, the benefits of robust AMR surveillance far outweigh these challenges. Early detection of emerging resistance patterns allows for swift public health responses to contain and manage outbreaks, protecting both local and global populations. Reliable surveillance data supports the development of evidence-based policies and guidelines for antimicrobial use, infection control, and prevention measures. At the national level, this data can help inform health policies and responses to health emergencies. At the global level, it can provide early warnings of emerging threats and help identify long-term trends, enhancing global health security and preparedness against potential pandemics caused by resistant pathogens.
The Path Forward
The 2024 BPPL emphasizes the need for a comprehensive public health approach to tackling AMR, including universal access to quality prevention, diagnosis, and treatment measures. However, it is important to recognize that different regions face variations in the types of bacteria present and the level of resistance they exhibit. Therefore, tailoring the list to specific regional contexts can enhance its effectiveness, allowing for more targeted interventions and resource allocation [3].
As the landscape of AMR continues to shift, regular updates to the list are essential to ensure ongoing focus on the most concerning threats. By combining antibiotic development with a comprehensive public health approach, we can win the fight against AMR and preserve the effectiveness of modern medicine.
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References
https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
https://www.who.int/news/item/17-05-2024-who-updates-list-of-drug-resistant-bacteria-most-threatening-to-human-health
https://www.cidrap.umn.edu/antimicrobial-stewardship/who-updates-bacterial-priority-pathogens-list