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The 2017 WHO Bacterial Priority Pathogens List (BPPL) has been instrumental in guiding global policy, research and development, and investments to address the most urgent threats from antibiotic-resistant pathogens, and it is a key public health tool for the prevention and control of antimicrobial resistance (AMR). Since its release, at least 13 new antibiotics targeting bacterial priority pathogens have been approved. The 2024 WHO BPPL aims to refine and build on the previous list by incorporating new data and evidence, addressing previous limitations, and improving pathogen prioritisation to better guide global efforts in combating AMR. The 2024 WHO BPPL followed a similar approach to the first prioritisation exercise, using a multicriteria decision analysis framework. 24 antibiotic-resistant bacterial pathogens were scored based on eight criteria, including mortality, non-fatal burden, incidence, 10-year resistance trends, preventability, transmissibility, treatability, and antibacterial pipeline status. Pathogens were assessed on each of the criteria on the basis of available evidence and expert judgement. A preferences survey using a pairwise comparison was administered to 100 international experts (among whom 79 responded and 78 completed the survey) to determine the relative weights of the criteria. Applying these weights, the final ranking of pathogens was determined by calculating a total score in the range of 0–100% for each pathogen. Subgroup and sensitivity analyses were conducted to assess the impact of experts’ consistency, background, and geographical origin on the stability of the rankings. An independent advisory group reviewed the final list, and pathogens were subsequently streamlined and grouped into three priority tiers based on a quartile scoring system: critical (highest quartile), high (middle quartiles), and medium (lowest quartile). The pathogens’ total scores ranged from 84% for the top-ranked bacterium (carbapenem-resistant Klebsiella pneumoniae) to 28% for the bottom-ranked bacterium (penicillin-resistant group B streptococci). Antibiotic-resistant Gram-negative bacteria (including K pneumoniae, Acinetobacter spp, and Escherichia coli), as well as rifampicin-resistant Mycobacterium tuberculosis, were ranked in the highest quartile. Among the bacteria commonly responsible for community-acquired infections, the highest rankings were for fluoroquinolone-resistant Salmonella enterica serotype Typhi (72%), Shigella spp (70%), and Neisseria gonorrhoeae (64%). Other important pathogens on the list include Pseudomonas aeruginosa and Staphylococcus aureus. The results of the preferences survey showed a strong inter-rater agreement, with Spearman's rank correlation coefficient and Kendall's coefficient of concordance both at 0·9. The final ranking showed high stability, with clustering of the pathogens based on experts’ backgrounds and origins not resulting in any substantial changes to the ranking. The 2024 WHO BPPL is a key tool for prioritising research and development investments and informing global public health policies to combat AMR. Gram-negative bacteria and rifampicin-resistant M tuberculosis remain critical priority pathogens, underscoring their persistent threat and the limitations of the current antibacterial pipeline. Focused efforts and sustained investments in novel antibacterials are needed to address AMR priority pathogens, which include high-burden antibiotic-resistant bacteria such as Salmonella and Shigella spp, N gonorrhoeae, and S aureus. Beyond research and development, efforts to address these pathogens should also include expanding equitable access to existing drugs, enhancing vaccine coverage, and strengthening infection prevention and control measures. This work is based on the development of the 2024 WHO BPPL, which was conducted by the WHO AMR Division through grants from the Government of Austria, the Government of Germany, the Government of Saudi Arabia, and the European Commission's Health Emergency Preparedness and Response Authority. For the Arabic, French, Italian, Japanese and Spanish translations of the abstract see Supplementary Materials section.

On May 19, 2014, the 67th World Health Assembly (WHA) adopted WHO's \"Global strategy and targets for tuberculosis prevention, care and control after 2015\". This post-2015 global tuberculosis strategy, labelled the End TB Strategy, was shaped during the past 2 years.

Tuberculosis (TB) is the most deadly infectious disease globally. Although most individuals achieve a cure, a substantial portion develop multi-drug resistant TB which is exceedingly difficult to treat, and the number of effective agents is dwindling. Development of new anti-tubercular medications is imperative to combat existing drug resistance and accelerate global eradication of TB. Pretomanid (PA-824) represents one of the newest drug classes (ie, nitroimidazooxazines) approved in 2019 by the United States Food and Drug Administration as part of a multi-drug regimen (with bedaquiline and linezolid, BPaL) and recommended by the World Health Organization (WHO) to treat extensively-resistant (XR-TB) and multi-drug resistant tuberculosis (MDR-TB). Approval was granted through the FDA's Limited Population Pathway for Antibacterial and Antifungal Drugs, which accelerates approval for antimicrobial drugs used to treat life-threatening or serious infections in a limited population with unmet need. This review details the pharmacology, efficacy, and safety of this new agent and describes evidence to date for its role in the treatment of drug resistant TB including published, ongoing, and planned studies.

In 2020, almost half a million individuals developed rifampicin-resistant tuberculosis (RR-TB). We estimated the global burden of RR-TB over the lifetime of affected individuals. We synthesized data on incidence, case detection, and treatment outcomes in 192 countries (99.99% of global tuberculosis). Using a mathematical model, we projected disability-adjusted life years (DALYs) over the lifetime for individuals developing tuberculosis in 2020 stratified by country, age, sex, HIV, and rifampicin resistance. Here we show that incident RR-TB in 2020 was responsible for an estimated 6.9 (95% uncertainty interval: 5.5, 8.5) million DALYs, 44% (31, 54) of which accrued among TB survivors. We estimated an average of 17 (14, 21) DALYs per person developing RR-TB, 34% (12, 56) greater than for rifampicin-susceptible tuberculosis. RR-TB burden per 100,000 was highest in former Soviet Union countries and southern African countries. While RR-TB causes substantial short-term morbidity and mortality, nearly half of the overall disease burden of RR-TB accrues among tuberculosis survivors. The substantial long-term health impacts among those surviving RR-TB disease suggest the need for improved post-treatment care and further justify increased health expenditures to prevent RR-TB transmission. Rifampicin-resistant tuberculosis (RR-TB) requires longer, more toxic therapy than rifampicin-sensitive disease and is associated with a higher occurrence of long-term sequelae. In this mathematical modeling study, the authors estimate that incident RR-TB in 2020 will be responsible for ~6.9 million disability-adjusted life years; 44% due to post-tuberculosis sequelae.

International policy for treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR TB) relies largely on individual patient data (IPD) from observational studies of patients treated under routine conditions. We prepared guidance on which data to collect and what measures could improve consistency and utility for future evidence-based recommendations. We highlight critical stages in data collection at which improvements to uniformity, accuracy, and completeness could add value to IPD quality. Through a repetitive development process, we suggest essential patient- and treatment-related characteristics that should be collected by prospective contributors of observational IPD in MDR/RR TB.

Tuberculosis (TB) remains the foremost cause of death by an infectious disease globally. Multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB; resistance to rifampicin and isoniazid, or rifampicin alone) is a burgeoning public health challenge in several parts of the world, and especially Eastern Europe, Russia, Asia and sub-Saharan Africa. Pre-extensively drug-resistant TB (pre-XDR-TB) refers to MDR/RR-TB that is also resistant to a fluoroquinolone, and extensively drug-resistant TB (XDR-TB) isolates are additionally resistant to other key drugs such as bedaquiline and/or linezolid. Collectively, these subgroups are referred to as drug-resistant TB (DR-TB). All forms of DR-TB can be as transmissible as rifampicin-susceptible TB; however, it is more difficult to diagnose, is associated with higher mortality and morbidity, and higher rates of post-TB lung damage. The various forms of DR-TB often consume >50% of national TB budgets despite comprising <5–10% of the total TB case-load. The past decade has seen a dramatic change in the DR-TB treatment landscape with the introduction of new diagnostics and therapeutic agents. However, there is limited guidance on understanding and managing various aspects of this complex entity, including the pathogenesis, transmission, diagnosis, management and prevention of MDR-TB and XDR-TB, especially at the primary care physician level. Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis that is resistant to several first-line drugs. MDR-TB is an increasing public health challenge. In this Primer, Dheda et al. summarize the epidemiology and mechanisms, and discuss diagnosis, management and quality of life of patients with MDR-TB.

Guideline development groups or other health care decision makers frequently encounter situations that require a simultaneous comparison of multiple interventions. This sometimes becomes apparent either when they identify questions of interest, before they formulate recommendations, or it may surface only when recommendations have already been formulated based on pairwise comparisons. Using examples from the World Health Organization, the European Commission, and a professional society, we developed a flexible approach to developing recommendations when a multiple-intervention comparison (MC) is needed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence to decision (EtD) frameworks. We iteratively refined this approach through user testing and then included a module in GRADE's official software GRADEpro to test the approach in two real and one theoretical guideline recommendations. We found the approach feasible and that all EtD criteria should be considered in an MC approach. We judged that guideline development groups and other decision makers will benefit from the availability of a network meta-analyses (NMA) of intervention effects to support decisions; however, NMA supports only one of many criteria, that is, the balance of health benefits and harms, and is therefore helpful, but not essential to the approach we propose. When similar but not identical comparators are used to address MC, challenges may arise with intransitivity and the relative rankings of interventions. We successfully applied the MC approach and software module in generating recommendations across different scenarios and identified challenges. The MC approach allows guideline groups and other decision makers to transparently and critically assess multiple options for a given health question. Application of the approach by others may lead to refinement and allow for better understanding of its impact in developing recommendations and making choices.

Simpler, shorter, safer and more effective treatments for tuberculosis that are easily accessible to all people with tuberculosis are desperately needed. In 2016, the World Health Organization (WHO) developed target regimen profiles for the treatment of tuberculosis to make drug developers aware of both the important features of treatment regimens, and patient and programmatic needs at the country level. In view of recent ground-breaking advances in tuberculosis treatment, WHO has revised and updated these regimen profiles. We used a similar process as for the 2016 profiles, including a baseline treatment landscape analysis, an initial stakeholder survey, modelling studies estimating the impact and cost-effectiveness of novel tuberculosis treatment regimens, and an extensive stakeholder consultation. We developed target regimen profiles for the treatment of rifampicin-susceptible and rifampicin-resistant tuberculosis, as well as a pan-tuberculosis regimen that would be appropriate for patients with any type of tuberculosis. We describe the revised target regimen profile characteristics, with specific minimal and optimal targets to be met, rationale and justification, and aspects relevant to all target regimen profiles (drug susceptibility testing, adherence and forgiveness, treatment strategies, post-tuberculosis lung disease, and cost and access considerations). We discuss the trade-offs of proposed characteristics for decision-making at developmental or operational levels. We expect that, following these target regimen profile revisions, tuberculosis treatment developers will produce regimens that are quality-assured, affordable and widely available, and that meet the needs of affected populations.

Having up-to-date health policy recommendations accessible in one location is in high demand by guideline users. We developed an easy to navigate interactive approach to organize recommendations and applied it to tuberculosis (TB) guidelines of the World Health Organization (WHO). We used a mixed-methods study design to develop a framework for recommendation mapping with seven key methodological considerations. We define a recommendation map as an online repository of recommendations from several guidelines on a condition, providing links to the underlying evidence and expert judgments that inform them, allowing users to filter and cross-tabulate the search results. We engaged guideline developers, users, and health software engineers in an iterative process to elaborate the WHO eTB recommendation map. Applying the seven-step framework, we included 228 recommendations, linked to 103 guideline questions and organized the recommendation map according to key components of the health question, including the original recommendations and rationale (https://who.tuberculosis.recmap.org/). The recommendation mapping framework provides the entire continuum of evidence mapping by framing recommendations within a guideline questions’ population, interventions, and comparators domains. Recommendation maps should allow guideline developers to organize their work meaningfully, standardize the automated publication of guidelines through links to the GRADEpro guideline development tool, and increase their accessibility and usability. •What this adds to what is known: This work transfers evidence mapping methods to guidelines in a process we call “recommendation mapping.”•What is the implication, what should change now: Recommendation mapping provides a digital curation of guidelines for a particular condition or disease. In this article we describe how we created an online map of WHO guidance on tuberculosis prevention and care to enhance accessibility of recommendation data and other key guideline components, facilitate their prompt update as needed, allow cross-tabulation of recommendations to help visualize any priority gaps and clustering and facilitate the adaptation of recommendations by users.•Recommendation maps are accessory to the notion of “living guidelines” that are promptly updated to reflect the state of the science, providing a digital solution to improve upon the organization, accessibility, and ultimately, uptake of guideline recommendations to benefit individual wellbeing or public health. It is directly linked to the GRADEpro guideline development tool. [Display omitted]

Background: Simultaneous use of genotypic and phenotypic diagnostic tools for detection of rifampicin (RIF) susceptibility may yield discrepant results. Objective: To measure the discordance between the RIF-susceptibility results by Xpert MTB/RIF and Mycobacterium Growth Indicator Tube (MGIT), to evaluate if application of both tests to the same sample affects the discrepancy, and to evaluate treatment outcome in patients with the discordant strains. Design: Sputa from patients with tuberculosis managed in the penitentiary system of Azerbaijan during 2011–2015 were examined for RIF susceptibility using Xpert MTB/RIF and MGIT. Strains with discrepant results were sequenced. Results: Of 532 patients included, 6.2% had discordant RIF-susceptibility results. No significant association of the discordant RIF-susceptibility results with application of both tests on one sample versus sequential samples was found. L511P mutation accounted significantly ( p  = 0.006) for the discrepancy among those RIF resistant on Xpert MTB/RIF, but sensitive on MGIT. No significant association was identified between the outcomes of treatment with the first- or second-line drugs and the presence of any mutation. Conclusion: The Xpert MTB/RIF and MGIT testing may be used in sequential sputum samples without increase in the RIF-susceptibility discordance rate. L511P mutation significantly accounts for discordant RIF-susceptibility results, but its clinical relevance may be low.