WHO outlines 40 research priorities on antimicrobial resistance

WHO has published its first global research agenda for the world’s scientists to address the most urgent human health priorities to combat antimicrobial resistance (AMR). It outlines 40 research topics on drug-resistant bacteria, fungi and Mycobacterium tuberculosis that must be answered by 2030, in line with the Sustainable Development Goals.

The WHO Global Research Agenda for AMR in human health will catalyze innovation and implementation research, spanning the epidemiology, burden and drivers of AMR, context-specific and cost-effective strategies to prevent infections and emergence of resistance.

It will also involve the discovery of new diagnostic tests and improved treatment regimens, the identification of cost-effective methods to collect data and translate it into policy, as well as how to implement current interventions more efficiently in resource-limited settings. Ultimately, the generated evidence will inform policies and interventions to strengthen the response to antimicrobial resistance, particularly in low- and middle-income countries.

“Antimicrobial resistance is an urgent public health and economic challenge, and good quality research is a vital part of the response. To help preserve antimicrobials and save lives and livelihoods, this research agenda is a crucial tool for researchers and funders to prioritize research questions, and promptly and efficiently generate evidence that informs policy,” said Dr Hanan Balkhy, WHO Assistant Director-General for AMR. “This first research agenda from WHO will provide the world’s AMR researchers and funders with the most important topics to focus on and give the world its best chance to combat AMR,” added Dr Silvia Bertagnolio, Unit Head in WHO AMR Division.

The research agenda was developed based on a review of over 3000 relevant documents published over the past decade. The review identified 2000 unanswered questions or knowledge gaps, which were further consolidated and prioritized by a large group of AMR experts to conclude with the 40 most pivotal research topics. A summary report containing the research priorities is available here.

AMR occurs when bacteria, viruses, fungi and parasites change over time and no longer respond to antimicrobial medicines making infections harder to treat and increasing the risk of disease spread, severe illness and death.

As a result, antimicrobial medicines become ineffective and infections persist in the body, increasing the risk of transmission to others. AMR remains one of the top global public health threats facing humanity and was associated with the death of close to 5 million people globally in 2019. Importantly, it is also a threat to the global economy, with impact on international trade, health care and productivity. If no action is taken, AMR could cost the world’s economy US$ 100 trillion by 2050.

Antimicrobial resistance research priorities

Prevention
Water, sanitation and hygiene (WASH)

• Investigate the impact, contribution, utility, effectiveness and cost–effectiveness of interventions to ensure safely managed water, sanitation and hygiene (including hand hygiene) and waste management practices in the community setting on reducing the burden and drivers of antimicrobial resistance, such as unnecessary antibiotic consumption for diarrhoeal diseases in low- and middle-income countries.
• Investigate implementation strategies of WASH-related interventions in health-care settings (including ensuring access to safely managed water and sanitation, safe hand hygiene, safe management of waste and environmental cleaning), and assess their impact, acceptability, equity and cost–effectiveness on the burden and transmission of resistant health care–associated infections and antimicrobial medicine prescribing across socioeconomic settings.

Infection, prevention and control

• Identify the most effective, cost–effective, acceptable and feasible multimodal infection and prevention control strategies (such as hand hygiene, contact precautions and patient isolation) and the relative effect of their components in reducing different types of health care–associated infections caused by multidrug-resistant pathogens across geographical and socioeconomic settings.

Immunization

• Assess the impact of vaccines on preventing colonization and infection by resistant pathogens (whether specifically targeted by the vaccine or not) and on reducing the overall use of antimicrobial medicines, health-care encounters and health system costs among adults and children, and across socioeconomic settings.

Diagnosis
Diagnosis and diagnostics

• Investigate and evaluate rapid point-of-care diagnostic tests (including biomarker-based tests) and diagnostic algorithms to discriminate between bacterial and viral infections and non-infectious syndromes that are feasible for use in limited-resource settings and among different subpopulations (including children and neonates).
• Investigate and evaluate phenotypic and genotypic methods of rapid antimicrobial susceptibility testing and resistance detection directly from positive blood culture bottles, especially for use in low- and middle-income countries.
• Investigate and evaluate diagnostic tests for isolating, identifying, antimicrobial susceptibility testing and/or detecting resistance of bacterial pathogens (including multiplex panel–based tests and tests using novel technologies) that are fast, (near) point of care, affordable, feasible for use in limited-resource settings and among different subpopulations and from a variety of specimen types.
• Investigate and evaluate rapid, (near) point-of-care diagnostic tests (including antigen and multiplex panel–based tests) for detecting drug-resistant WHO fungal priority pathogens with critical importance for antimicrobial resistance (such as Candida auris, Aspergillus fumigatus and Cryptococcus neoformans) feasible for use in limited-resource settings and among different subpopulations.
• Investigate and evaluate the clinical utility and diagnostic accuracy of phenotypic antifungal susceptibility testing (including determining minimal inhibitory concentration breakpoints and testing for in vitro and in vivo synergy between antifungal medicines) and their impact on clinical outcomes.
• Investigate, assess the performance and evaluate the implementation of novel rapid point-of-care molecular and non- molecular assays and optimal testing and screening approaches (including self-testing) for Neisseria gonorrhoeae and antimicrobial resistance detection to reduce inappropriate antibiotic prescribing and emergence of antimicrobial resistance.

Treatment and care
Antimicrobial stewardship

• Investigate antimicrobial stewardship interventions (such as implementing the WHO AWaRe antibiotic book,11 guidelines, clinical algorithms, education and training, audit and feedback), alone or in combination, that are context specific, feasible, sustainable, effective and cost-effective to avoid antimicrobial misuse in outpatient and inpatient settings, especially where diagnostic capacity may be limited.
• Identify feasible, effective and scalable pharmacist antimicrobial medicines dispensing practices in community pharmacies and related regulatory frameworks (such as incentives and disincentives) to improve antimicrobial stewardship in the community, especially in low- and middle-income countries.
• Investigate criteria and strategies to optimize empirical antimicrobial therapy (such as antimicrobial spectrum, dose, timing of initiation, de-escalation, and stopping), weighting the benefits (e.g., improve outcomes, reduce cost) versus potential harms (e.g., clinical failure, infection relapse, resistance emergence, adverse events), for main community and health care-associated infectious syndromes in adults and children, especially in settings where medicine availability, diagnostic capacity and access to health care services may be limited.

Antimicrobial use and consumption

• Determine optimal (feasible, accurate and cost-effective) methods and metrics to monitor antimicrobial use and consumption in the community and health-care settings and appropriate targets to monitor progress in reducing inappropriate antimicrobial use and consumption.
• Determine the levels, patterns, trends and drivers of appropriate and inappropriate prescribing, use and consumption of access, watch and reserve (AWaRe) antibiotics11 across countries and community and health-care settings, with data disaggregated by sex, age, socioeconomic status and subpopulations, including those experiencing vulnerability and with comorbidities (such as people living with HIV, people with TB and people with malaria).
• Investigate optimal approaches to effectively use facility- and/ or national-level antimicrobial consumption and antimicrobial resistance surveillance data to inform antimicrobial stewardship programmes and treatment guidelines.

Antimicrobial medicines

• Investigate efficacious and safe antibiotic treatment regimens based on old and new agents and combinations for infections, especially for extended-spectrum beta-lactamase producing and/or carbapenem-resistant Enterobacterales, with minimum selection and transmission risk for antimicrobial resistance, especially among children and other subpopulations experiencing vulnerability.
• Investigate efficacious and safe antibiotic treatment regimens for infections by drug resistant typhoid and non-typhoidal salmonellae (including for pathogens resistant to cephalosporins and fluoroquinolones) across socioeconomic settings.
• Investigate efficacious and safe empirical antibiotic treatment (drug choice, drug combination, route, dose and duration) for gram-negative bacteria causing bloodstream infections or sepsis among neonates and young children, especially in settings with high antimicrobial resistance prevalence, limited diagnostic capacity, and antimicrobial medicine availability.
• Investigate antifungal regimens optimized for efficacy, cost, safety and duration for the treatment of infections caused by WHO fungal priority pathogens with critical importance for antimicrobial resistance (such as Candida auris, Aspergillus fumigatus and
• Cryptococcus neoformans) in settings with increasing or high prevalence of antifungal resistance.
• Investigate efficacious and safe regimens based on new or existing antimicrobial medicines for urogenital and extragenital sexually transmitted infections (such as resistant Neisseria gonorrhoeae and resistant Mycoplasma genitalium) in the context of increasing antimicrobial resistance levels, including in populations experiencing vulnerability (such as people living with HIV, pregnant women and adolescents).

Cross-cutting

• Antimicrobial resistance epidemiology, burden and drivers Investigate the prevalence, incidence, mortality, morbidity and socioeconomic impact of community acquired infections (respiratory tract infections, urinary tract infections and bloodstream infections) and health care–associated infections (bloodstream infections, urinary tract infections, surgical site infections and respiratory tract infections) by resistant WHO bacterial priority pathogens, with data disaggregated by sex, age, socioeconomic status and subpopulations (e.g. populations experiencing vulnerability or with comorbidities such as people living with HIV, people with TB and people with malaria) and across socioeconomic settings, especially in low- and middle-income countries.
• Investigate the prevalence, incidence, morbidity, mortality and socioeconomic impact, and identify and quantify the routes and dynamic of infections by resistant WHO fungal priority pathogens with critical importance for antimicrobial resistance (such as Candida auris, Aspergillus fumigatus and Cryptococcus neoformans) across geographical and socioeconomic settings and in populations experiencing vulnerability.
• Investigate the association, contribution and impact of structural and health system factors (such as hospital microbiome, sanitation infrastructure, waste management, health expenditure, governance, distribution of resources, population displacement, conflict and disruptions in the care continuum) on colonization (selection, persistence and spread or loss of bacterial populations) and infection by WHO bacterial and fungal priority pathogens in various subpopulations, including those experiencing vulnerability (such as migrants and refugees) and people with comorbidities, across various socioeconomic settings.
• Identify optimal (efficient, effective and cost-effective) surveillance methods to generate accurate and reliable data on the epidemiology and burden of antimicrobial resistance among WHO bacterial and fungal
• priority pathogens (including determining the genotypic predictors of resistance), in community and health-care settings and disaggregated by sex, age and subpopulations that are relevant and actionable at the local and national levels, especially in low- and middle-income countries.
• Assess the short- and long-term impact on antimicrobial resistance of the programmatic use of antimicrobial medicines in mass administration, focusing on subpopulations experiencing vulnerability in low-income settings.
• Evaluate the public health benefits, cost, impact on unnecessary or inappropriate antibiotic prescribing and potential antimicrobial resistance consequences of currently recommended syndromic sexually transmitted infection management and treatment of people with asymptomatic
• sexually transmitted infections (including Neisseria gonorrhoeae) in
• settings with variable diagnostic capacity.

Antimicrobial resistance awareness and education

• Determine the most (cost-) effective behavioural change interventions to mitigate antimicrobial resistance emergence and spread by targeting and engaging the general public, young people, mass media, health-care providers and policy-makers across socioeconomic settings.
• Policies and regulations related to antimicrobial resistance
• Evaluate the implementation of antimicrobial resistance–related policies and regulations at the national level and their effectiveness in mitigating antimicrobial resistance and improving health outcomes in the community and health-care settings across socioeconomic contexts.
• Investigate strategies for the sustainable and (cost-) effective implementation of national policies, legislation and regulations
• (including sustainable financing and optimal governance structures) to improve infection prevention and patient care practices and the use of antimicrobial medicines in the community and health-care settings, across socioeconomic contexts.
• Identify the most (cost-) effective interventions to mitigate antimicrobial resistance in the human health sector, globally and within countries or regions, and determine the rationale, costs, benefits, feasibility, sustainability and potential returns on investment to achieve the greatest benefit.
• Investigate strategies to integrate antimicrobial resistance interventions into broader health, health financing, development, welfare structures and national policies, and evaluate their impact on mitigating antimicrobial resistance, enhancing health system efficiency, reducing people’s out-of-pocket expenses and improving equitable access to and use of diagnostics and antimicrobial medicines.
• Investigate how existing regulatory frameworks, marketing incentives (or their absence) and sustainable financing models affect the development and availability of new antimicrobial medicines and identify effective strategies to adapt these approaches to low-income settings to improve availability for adults and children.

Drug-resistant TB
Prevention

• Investigate effective preventive TB vaccines that meet WHO preferred product characteristics criteria and demonstrate impact on preventing infection, disease, and recurrence (relapse or reinfection) and thereby preventing or reducing the incidence of drug-resistant TB.

Diagnosis

• Investigate how the diagnostic performance of molecular assays can be improved to detect drug resistance among people with extrapulmonary and pulmonary TB, from non-respiratory specimens, including among children and adolescents.
• Determine optimal diagnostic and treatment delivery models to improve the access, effectiveness, cost–effectiveness, feasibility and acceptability of drug-resistant TB testing and treatment across settings and subpopulations (such as people living with HIV, children and adolescents, and prisoners) and evaluate their impact on reducing drug- resistant TB at the population level.

Treatment and care

• Investigate better tolerated, optimally dosed, more effective and shorter combination regimens, using a stratified risk approach, for treating all forms of drug-resistant TB, including in populations experiencing vulnerability (such as children, pregnant and breastfeeding women, and people living with HIV).
• Determine the optimal, (cost-) effective, shortest duration and safest TB preventive treatment for the contacts of people with drug- resistant TB, especially among people at high-risk of TB infection and disease, as identified in WHO guidance, and eligible populations experiencing vulnerability (such as children, adolescents, people living with HIV and pregnant women).
• Investigate strategies for improving treatment outcomes among people with drug-resistant TB who have known risk factors and co-occurring conditions (such as HIV, undernutrition, diabetes mellitus, tobacco use, alcohol and other substance use, and mental health disorders), and populations experiencing vulnerability (such as pregnant and breastfeeding women, children, adolescents and prisoners) in various geographical and socioeconomic settings.
• Investigate the programmatic effectiveness, safety and tolerability of currently used WHO recommended treatment regimens for drug- resistant TB (including combinations with bedaquiline, delamanid and/ or pretomanid) on patient outcomes and drug-resistant TB emergence across populations and settings and identify the drivers of treatment failure.