The 2024 WHO Bacterial Priority Pathogens List (WHO BPPL) is an important tool in the global fight against antimicrobial resistance. Building on the 2017 edition, the 2024 WHO BPPL updates and refines the prioritization of antibiotic-resistant bacterial pathogens to address the evolving challenges of antibiotic resistance. The 2024 WHO BPPL covers 24 pathogens, spanning 15 families of antibiotic-resistant bacterial pathogens. Notable among these are Gram-negative bacteria resistant to last-resort antibiotics, drug-resistant mycobacterium tuberculosis, and other high-burden resistant pathogens such as Salmonella, Shigella, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Staphylococcus aureus. Moreover, the first on the 2024 WHO BPPL is carbapenem-resistant Klebsiella pneumoniae, followed by third generation cephalosporine resistantE. coli and carbapenem resistant A. baumanni . Notably,the most important new pathogen is rifampicin-resistant Mycobacterium tubercolosis, at the fourth place. The inclusion of these pathogens in the list underscores their global impact in terms of burden, as well as issues related to transmissibility, treatability, and prevention options. It also reflects the R&D pipeline of new treatments and emerging resistance trends. The WHO BPPL acts as a guide for prioritizing R&D and investments in AMR, emphasizing the need for regionally tailored strategies to effectively combat resistance. It targets developers of antibacterial medicines, academic and public research institutions, research funders, and public–private partnerships investing in AMR R&D, as well as policy-makers responsible for developing and implementing AMR policies and programs.
Will Quince (Member of the United Kingdom Parliament) has moved to the House of British Parliament the antimicrobial resistance alarm, that there is a problem so serious that it poses a major threat to global health from the World Health Organisation (WHO) and it’s on the UK’s national risk register and is costing the National Health Service around £180 million per year. Particularly, he referred that in the UK deaths related to this problem are estimated at 12,000 per year and that 10 million people are expected to die every year globally from AMR problem if urgent measures are not taken. The consequences of antimicrobial resistance are enormous. This makes it more difficult to effectively treat common infections. AMR is putting the advances of modern medicine at risk, because it makes surgical and medical procedures that are part of everyday life – such as caesarean sections, cancer chemotherapy and hip replacements – much riskier. In addition to causing death and disability, antimicrobial resistance carries significant economic costs. AMR creates the need for more expensive and intensive care, affects the productivity of patients or their carers through prolonged hospital stays. The World Bank estimates that antimicrobial resistance could result in $1 trillion in additional health costs by 2050 and losses of $1 trillion to $3.4 trillion in GDP per year by 2030. W. Quince proposed Government for action in the AMR five-year national action plan, or NAP, to contain and control AMR by 2040, which the NHS long-term plan details commitments to implement. Consequently, he said a significant public awareness campaign, greater investment in diagnostics, monitoring and screening—particularly in relation to rapid point-of-care testing—at local system level and, vitally, greater focus on infection prevention and management are much needed. Finally, he spent the rest of the time focusing on international efforts and the role that the UK can play.
The Organization for Economic Co-operation and Development (OECD) has found that one in five infections, is now resistant to antibiotics, with the potential for that rate to double by 2035. If left unchecked, resistance to third-line antimicrobials—the last-resort drugs for difficult-to-treat infections—could be 2.1 times higher by 2035. That means that health systems will be closer to running out of options to treat patients suffering from a range of illnesses such as pneumonia and bloodstream infections. Preserving and optimising current antimicrobial arsenal is therefore not just urgent but paramount. The consequences of AMR are huge.
A new Global Leaders Group (GLG) report on AMR, calls on political leaders to make concrete and ambitious commitments at the high-level meeting on AMR to be held at the United Nations General Assembly on 26 Sept. 2024. The GLG report urges UN Member States to ensure that adequate, predictable, and sustainable financing is available from domestic and external sources to address AMR, including to tackle the dwindling research and development pipeline for new antibiotics, which proposes an independent panel be established to monitor and report on science and evidence related to AMR to inform advocacy and action and formalizing the Quadripartite Joint Secretariat to facilitate collaborative and coordinated action against AMR. Moreover, the GLG stresses the need for improved quality of data on AMR and use surveillance and monitoring and recommends that countries strengthen human resources and crucial infrastructure capacity. The report highlights the need for sustainable, sector-specific, and integrated surveillance systems and the use of data for action.
To drive Global and National action on AMR, the GLG report proposes several outcome-oriented targets to accelerate progress by 2030:
- reduce global human deaths due to AMR by 10%.
- ACCESS group antibiotics comprise at least 80% of overall human antibiotic consumption.
- reduce the quantity of antimicrobials used in the agri-food system globally by at least 30-50% from the current level;
- eliminate the use of medically important antimicrobials for human medicine in animals for non-veterinary medical purposes, or in crop production and agri-food systems for non-phytosanitary purposes.
New evidence from the World Health Organization (WHO) shows the extensive overuse of antibiotics (ABs) during COVID-19 pandemic worldwide, which may have exacerbated “silent” spread of antimicrobial resistance (AMR). While only 8% of hospitalized patients with COVID-19 had bacterial co-infections requiring ABs, three out of four or some 75% of patients have been treated with ABs ‘just in case’ they help. Antibiotic use ranged from 33% for patients in the Western Pacific Region, to 83% in the Eastern Mediterranean and the African Regions. Between 2020 and 2022, highest rate of AB use was seen among patients with severe or critical COVID-19, with a global average of 81%. In mild or moderate cases, there was a considerable variation across regions, with the highest use in the African Region (79%). These findings are based on data from the WHO Global Clinical Platform for COVID-19, a repository of standardized individual-level, anonymized clinical data from patients hospitalized with COVID-19. Data was collected from some 450.000 patients admitted to hospitals for COVID-19 in 65 countries over a 3-year period between January 2020 to March 2023. The findings are being presented in a WHO scientific poster shared at the ESCMID Global Congress, held in Barcelona, Spain on 27-30 April 2024. “These findings underscore the important need to adequately resource the efforts to improve antibiotic prescribing globally, and are particularly relevant to discuss ahead of the upcoming UN General Assembly High-Level Meeting on AMR to take place this September,” said Dr Yukiko Nakatani, WHO Assistant Director-General for AMR. The UN High-Level meeting on AMR will bring together global leaders to commit to mitigating AMR across human health, animal health, agri-food sectors and the environment, and to promote political leadership, financing and actions to slow the emergence and spread of AMR.
International guidelines on the development of new antibiotics for emergence of multidrug-resistant Gram-negative bacilli, are valuable tools, though limited by scarcity of high-quality randomized trials in many situations. A panel of experts from the French and Italian Societies of Infectious Diseases aimed to address unresolved issues in clinical practice based on their experience, updated literature review, and open discussions. The panel reached a consensus for the following ‘first-choices’: i) cefepime for ventilator-acquired pneumonia due to AmpC β-lactamase-producing Enterobacterales; ii) The β-lactam/β-lactamase inhibitors combination most active in vitro, or cefiderocol combined with fosfomycin, and aerosolized colistin or aminoglycosides, for severe pneumonia due to P.aeruginosa resistant to ceftolozane-tazobactam; iii) high-dose piperacillin-tazobactam (including loading dose and continuous infusion), for complicated urinary tract infections (cUTIs) caused by ESBL-producing Enterobacterales with piperacillin-tazobactam MIC ≤8 mg/L; iv) high-dose cefepime for cUTIs due to AmpC β-lactamase-producing Enterobacterales other than Enterobacter spp. if cefepime MIC ≤2 mg/L; v) ceftolozane-tazobactam or ceftazidime-avibactam plus metronidazole for intra-abdominal infections (IAIs) due to 3rd generation cephalosporin-resistant Enterobacterales; vi) ceftazidime-avibactam plus aztreonam plus metronidazole for IAIs due to metallo β-lactamase-producing Enterobacterales; vii) ampicillin-sulbactam plus colistin for bloodstream infections (BSIs) caused by carbapenem-resistant A. baumannii (CRAB); viii) meropenem-vaborbactam for BSI caused by KPC-producing Enterobacterales; ix) ceftazidime-avibactam plus fosfomycin for neurological infections caused by carbapenem-resistant P. aeruginosa.
International guidelines on the development of new antibiotics for emergence of multidrug-resistant Gram-negative bacilli, are valuable tools, though limited by scarcity of high-quality randomized trials in many situations. A panel of experts from the French and Italian Societies of Infectious Diseases aimed to address unresolved issues in clinical practice based on their experience, updated literature review, and open discussions. The panel reached a consensus for the following ‘first-choices’: i) cefepime for ventilator-acquired pneumonia due to AmpC β-lactamase-producing Enterobacterales; ii) The β-lactam/β-lactamase inhibitors combination most active in vitro, or cefiderocol combined with fosfomycin, and aerosolized colistin or aminoglycosides, for severe pneumonia due to P.aeruginosa resistant to ceftolozane-tazobactam; iii) high-dose piperacillin-tazobactam (including loading dose and continuous infusion), for complicated urinary tract infections (cUTIs) caused by ESBL-producing Enterobacterales with piperacillin-tazobactam MIC ≤8 mg/L; iv) high-dose cefepime for cUTIs due to AmpC β-lactamase-producing Enterobacterales other than Enterobacter spp. if cefepime MIC ≤2 mg/L; v) ceftolozane-tazobactam or ceftazidime-avibactam plus metronidazole for intra-abdominal infections (IAIs) due to 3rd generation cephalosporin-resistant Enterobacterales; vi) ceftazidime-avibactam plus aztreonam plus metronidazole for IAIs due to metallo β-lactamase-producing Enterobacterales; vii) ampicillin-sulbactam plus colistin for bloodstream infections (BSIs) caused by carbapenem-resistant A. baumannii (CRAB); viii) meropenem-vaborbactam for BSI caused by KPC-producing Enterobacterales; ix) ceftazidime-avibactam plus fosfomycin for neurological infections caused by carbapenem-resistant P. aeruginosa.
This retrospective cohort study included adults (aged ≥18 years) admitted to hospital with ECR Enterobacterales infections in the PINC AI database. Between Jan 1, 2018, and Dec 31, 2021, 30.041 inpatient encounters with ECR Enterobacterales infections were identified at 168 US hospitals, of which 16 006 (53·3%) encounters were in women and 14 035 (46·7%) were in men, with a mean age of 67·3 years. Although few patients received carbapenems empirically (5324 [17·7%] of 30 041), many did so as targeted treatment (17 518 [58·3%] of 30 041), including subgroups of patients without septic shock (3031 [45·6%] of 6651) and patients with urinary tract infections without septic shock (1845 [46·8%] of 3943) in whom specific narrower-spectrum alternatives were active. Carbapenems were the predominant choice to treat ECR Enterobacterales infections over time (adjusted odds ratio 1·00 [95% CI 1·00–1·00]), with no additional immediate change (1·07 [0·95–1·20]) or sustained change (0·99 [0·98–1·00]) after IDSA guidance release. High carbapenem use in targeting non-severe ECR Enterobacterales infections in US hospitals predates 2020 IDSA guidance and has persisted thereafter.
An estimated 70% of critically ill patients receive antibiotics, most frequently beta-lactams. The pharmacokinetic properties of these substances in this patient population are poorly predictable. Therapeutic drug monitoring (TDM) is helpful in making personalized decisions in this field, but its overall impact as a clinical decision-supporting tool is debated. Randomized controlled trials and observational studies were retrieved by searching three major databases. The intervention group received TDM-guided beta-lactam treatment, that is, at least one dose reconsideration based on the result of the measurement of drug concentrations, while TDM-unadjusted dosing was employed in the comparison group. Eight eligible studies were identified, including 1044 patients in total. TDM-guided beta-lactam treatment was associated with improved clinical cure from infection and microbiological eradication, as well as a lower probability of treatment failure, but the heterogeneity of studies was remarkably high, especially in terms of mortality (70%). The risk of bias was moderate. While the TDM-guided administration of beta-lactams to critically ill patients has a favourable impact, standardized study designs and larger sample sizes are required for developing evidence-based protocols in this field.