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Antibiotic innovation has slowed. Despite substantial public investment, research and development (R&D) remains insufficient to address rising antimicrobial resistance (AMR). In this historical review, we draw on quantitative and qualitative historiographic methodologies, as well as on testimony from key stakeholders, to reconstruct antibiotic innovation challenges and public interventions since 1980. Emerging in the 1990s and gaining traction around 2010, the “empty antibiotic pipeline” metaphor, as well as its market failure diagnosis, has played a key role in structuring the global R&D response. This reframing described AMR as an incentives-based innovation challenge, which suited industrial and high-income country interests. However, the introduction of so-called push and pull incentives has so far failed to halt the exit of large developers, sustain diversified R&D ecosystems, or address global access challenges. This article explores challenges and conflicts involved in the implementation of the incentives-based innovation approach alongside the ever-greater subsidies required to stabilise small and medium-sized enterprises (SMEs) and attract larger pharmaceutical companies and investment from financial markets. Several SME bankruptcies since 2019 and the mothballing of novel compounds suggest that this is an unsustainable innovation model. This article also explores whether public interventions have been insufficient or whether there is a deeper problem with the central metaphor structuring global action.
Antimicrobial resistance (AMR) is a global public health challenge that, like climate change, demands urgent, coordinated, multi-sectoral action. Yet, responses to AMR may be ill-suited to local contexts, overlook historical inequalities, or dismiss marginalised knowledge systems. Some of these concerns can be discussed using the concept of a just transition, which aims to ensure that “no one is left behind,” “all voices are heard,” and past injustices are addressed. However, framing justice in these terms is insufficient. We argue for a more multifaceted and broader-scoped understanding of what justice demands in a just transition for AMR. We examine existing justice frameworks in AMR literature and discuss two cases that motivate our call for including both more forms of justice in a multifaceted concept of a just transition and a broader scope of justice. The first case involves over-the-counter antibiotic access in the Kibera informal settlement near Nairobi, highlighting structural injustices resulting from colonial oppression and what an Ubuntu philosophy would show as injustice. The second case concerns veterinary prescription requirements for Maasai pastoralists’ livestock farming in southern Kenya and highlights epistemic and distributive injustices, as well as injustices that befall non-human animals. These examples reveal distinct injustices shaped by socio-cultural and ecological contexts.
Climate change, biodiversity loss, and antimicrobial pollution caused by human activity are placing pressure on global microbiota. However, microbial protection remains mostly absent from international law and global governance frameworks. This policy brief highlights the chronic marginalisation of microbes in international health, environmental, and human rights law, as well as in governance frameworks addressing antimicrobial resistance (AMR). Drawing on recent genomics and humanities research, it argues that policymakers need to abandon interventions designed to control or combat individual microbes in favour of microbiota-oriented governance. This brief discusses three major areas (pollution thresholds, microbial conservation, and the human right to a clean, healthy, and sustainable environment) where change is already occurring.
This study investigates the prevalence of coliform contamination in fresh milk and the occurrence of multidrug-resistant (MDR) bacteria within poultry environments on an integrated farm in Minna, Niger State. Bacterial isolates obtained from raw milk, poultry cloacal swabs, and intestinal swabs from commensal rats included Salmonella, Escherichia coli, and Klebsiella species. These isolates were screened for extended-spectrum beta-lactamase (ESBL) production and antimicrobial resistance profiles. The results revealed a high level of bacterial contamination in milk samples, with significant associations between contamination levels and poor hygiene practices during milking and handling. Moreover, ESBL-producing bacteria displaying resistance to critically important antibiotics such as third-generation cephalosporins and fluoroquinolones were identified across both dairy and poultry sources. These findings highlight a pressing public health concern and emphasize the need for improved biosecurity, hygiene interventions and integrated antimicrobial resistance surveillance to safeguard food safety and reduce the spread of MDR pathogens in animal-source foods.
Antimicrobials are widely used to maintain animal health and productivity; however, their misuse contributes to antimicrobial resistance (AMR), a critical One Health and global health concern. This study assessed the knowledge, awareness, and practices of animal health practitioners regarding antimicrobial use and AMR in Niger State, Nigeria. A questionnaire-based cross-sectional survey was conducted using purposive sampling, and data were analyzed at a 95% confidence level. A total of 62.8% of targeted practitioners participated. About 42.3% used antimicrobials for treating infections, while 12.2% used them for growth promotion. Only 19.5% correctly identified misuse as under-dosing, and 13.0% were unaware of what misuse entailed. Although 69.1% adhered to daily dosages as prescribed, only 1.6% performed confirmatory diagnoses before administration. Tetracycline (99.2%) and penicillin-streptomycin (82.1%) were the most frequently used antimicrobials. Satisfactory knowledge of antimicrobial use was significantly associated with practitioners aged 50–59 years (p = 0.002) and veterinarians (p = 0.001). Factors influencing misuse included improper usage (p < 0.001), weak regulation (p = 0.005), poor client finances (p = 0.001), low expertise (p = 0.001), and counterfeit drugs (p = 0.001). The findings underscore the urgent need for antimicrobial stewardship, stricter regulation, and continuous education of animal health practitioners.
Antimicrobial resistance is a multidisciplinary issue that has been high in the global agenda since the 2015 WHO Global Action Plan (GAP) and the 2016 UNGA Declaration. The Quadripartite Coalition has set up a consolidated global governance structure to coordinate AMR responses, including a Global Leaders Group, an Independent Panel of Experts and a stakeholders’ platform. At the national level, countries have set up more or less formal mechanisms to coordinate AMR management, develop and implement National Action Plans.
This chapter will draw on these pilot experiences to identify options for broader One Health governance and regulation. The chapter will examine global and regional governance and regulation of AMR – focusing on the EU as a case study – to explore possible applications to other priority areas such as zoonotic diseases.
The COVID-19 pandemic revealed the fractured state of global health law infrastructure. Establishing a One Health framework in law and policy is necessary to address the multitude of interlinked global health and sustainability challenges, including the risk of emerging and re-emerging infectious diseases, climate change, antimicrobial resistance, and food insecurity. This chapter will look at domestic and regional institutional collaborative frameworks focused on One Health, drawing on the development and implementation of integrated frameworks at the country level including, Egypt, Vietnam, Kenya, and India. Additionally, it will see how regional cooperation in the Arctic has led to the adoption and implementation of One Health policy guidelines and frameworks at the domestic level. The examination of national approaches will provide a critical analysis of key opportunities and barriers for domestic policy guidelines moving forward.
Antimicrobial resistant infections are expected to increase the rate of antibiotic treatment failure in patients during a mass casualty incident. We aim to examine the potential impact of rising antimicrobial resistance (AMR) on medical preparedness and response to a nuclear detonation in the United States (U.S.) using a model to estimate the number of casualties with secondary bacterial infections overlaid with real-world data on the burden of antibiotic-resistant pathogens.
Methods
The population of injured individuals needing treatment was estimated from a simulation involving a 100-kiloton nuclear detonation in a major U.S. metropolitan area. Contemporary antibiotic resistance rates for eight key bacterial pathogens were derived from the SENTRY Microbiology Visualization Platform.
Results
Our model estimated that up to 65% of the casualties could be at risk to develop a secondary bacterial infection requiring antibiotic treatment which, when combined with the increasing burden of AMR in U.S., could result in up to one third of those patients who are injured and infected being at risk for treatment failure due to antibiotic resistance.
Conclusions
The burden of AMR on the emergency response to a mass casualty incident, as described, could be a significant hinderance to efforts to treat infections and protect lives.
Objective: Antimicrobial resistance will become one of the most lethal conditions, which will raise burdens in many sectors across the One Health spectrum. The irrational use of antibiotics without proper monitoring is one of the causes of antimicrobial resistance. The quality of antimicrobial usage could be evaluated quantitatively using the Defined Daily Dose (DDD) method and qualitatively using the Gyssens method. This study aims to evaluate the antimicrobial usage qualitatively. Method: This is a retrospective study using data from the electronic medical record of Adam Malik Hospital within the period of July 2022–December 2023. All adult patients (>18 years old) in the internal medicine ward with a history of antimicrobial prescriptions were included in this study. The quality evaluation was carried out by the researchers, of whom three of them are members of the hospital’s antimicrobial stewardship program (PPRA) team. Result: There are 293 cases of antimicrobial use included in this study. Most of the population in this study was female (51.9%), in the 18–59 year group (74.1%), and respiratory tract infection was mostly diagnosed in this study (31.2%). Based on the Gyssens analysis, only 33% of cases of antimicrobial usage were appropriate (category 0). It means more than half of the antimicrobial use in internal medicine wards were irrational. Conclusion: The rationality of antimicrobial use is one of the most important ways to reduce the rate of antimicrobial resistance. This study shows only 33% of cases of appropriate antimicrobial usage, which is relatively low. Because irrational antimicrobial use can lead to antimicrobial resistance, prolonged length of stay and mortality, efforts need to be taken to improve the quality of antimicrobial use.
Bloodstream infections (BSIs) caused by Candida are a significant cause of morbidity and mortality. Geographical variations exist in the epidemiology of candidemia, with a paucity of data in the many low- and middle-income countries. We performed a retrospective study of candidemia from 2017 to 2022 at a 289-bed teaching hospital in the Dominican Republic (DR). A total of 197 cases were reviewed. Overall mortality rate was 49.2%. Age and vasopressor use were associated with mortality. The most prevalent Candida species were C. tropicalis and C. parapsilosis. C. albicans was 12% resistance to amphotericin B. These findings underscore the importance of understanding local epidemiology and may help inform empiric therapy and the development of treatment guidelines in the DR.
Antimicrobial resistance (AMR) has become a worldwide growing concern over the past decades. Thus, encouraging manufacturers to develop new antibiotics is needed. We hypothesised that transparency on the regulatory appraisals of antibiotics would provide an incentive to pharmaceutical development. We thus aimed at reporting the French health technology assessment (HTA) opinions and reimbursement decision on antibiotics to those German (G-BA) and English (NICE) HTA bodies.
A qualitative analysis of the Transparency Committee of the French National Authority for Health (TC-HAS) opinions regarding antibiotics assessment between 2016 and 2020 was performed. Decisions of reimbursement by TC-HAS were compared to those from G-BA and NICE when available. TC-HAS recognized a clinical benefit (CB) for 15/15 evaluated indications, a clinical added value for 9/15, and a public health interest for 8/15. Among the valued antibiotics by HAS, 5 were recommended for restricted use as a “reserve” to protect against the risk of resistance emergence. A comparison of HTA opinions was possible across HTA for only 8 antibiotics. The G-BA granted a reserve status for 4 drugs and NICE a reserve with restricted use for 5 antibiotics. Three of these antibiotics were positioned similarly by the English, German, and French HTA bodies. This qualitative analysis of HTA opinions between different European HTA bodies shows a consistent reimbursement decision of antibiotics against MDR bacteria and tuberculosis besides the differences in the applied assessment methods. This work also shows how HTA bodies could recognize a clinical added value in a context of the emergence of antibiotic resistance.
Reducing antimicrobial use (AMU) in livestock may be one of the keys to limit the emergence of antimicrobial resistance (AMR) in bacterial populations, including zoonotic pathogens. This study assessed the temporal association between AMU in livestock and AMR among Campylobacter isolates from human infections in the Netherlands between 2004 – 2020. Moreover, the associations between AMU and AMR in livestock and between AMR in livestock and AMR in human isolates were assessed. AMU and AMR data per antimicrobial class (tetracyclines, macrolides and fluoroquinolones) for Campylobacter jejuni and Campylobacter coli from poultry, cattle, and human patients were retrieved from national surveillance programs. Associations were assessed using logistic regression and the Spearman correlation test. Overall, there was an increasing trend in AMR among human C. jejuni/coli isolates during the study period, which contrasted with a decreasing trend in livestock AMU. In addition, stable trends in AMR in broilers were observed. No significant associations were observed between AMU and AMR in domestically produced broilers. Moderate to strong positive correlations were found between the yearly prevalence of AMR in broiler and human isolates. Reducing AMU in Dutch livestock alone may therefore not be sufficient to tackle the growing problem of AMR in Campylobacter among human cases in the Netherlands. More insight is needed regarding the population genetics and the evolutionary processes involved in resistance and fitness among Campylobacter.
We reviewed all diagnoses of Shigella species notified to the UK Health Security Agency from January 2016 to March 2023. An overall increase in notifications of shigellosis was seen between 2016 (n = 415/quarter) and 2023 (n = 1 029/quarter). However, notifications dramatically declined between March 2020 and September 2021 during the COVID-19 pandemic (n = 208/quarter) highlighting the impact of travel and social distancing restrictions on transmission. S. sonnei diagnoses were more affected by lockdown restrictions than S. flexneri, most likely due to a combination of species-specific characteristics and host attributes. Azithromycin resistance continued to be associated with epidemics of sexually transmissible S. flexneri (adult males = 45.6% vs. adult females = 8.7%) and S. sonnei (adult males = 59.5% vs. adult females = 14.6%). We detected resistance to ciprofloxacin in S. sonnei from adult male cases not reporting travel at a higher frequency (79.4%) than in travel-associated cases (61.7%). Extensively drug-resistant Shigella species associated with sexual transmission among men almost exclusively had ESBL encoded by blaCTX-M-27, whereas those associated with returning travellers had blaCTX-M-15. Given the increasing incidence of infections and AMR, we recommend that enhanced surveillance is used to better understand the impact of travel and sexual transmission on the acquisition and spread of MDR and XDR Shigella species.
Campylobacter spp. are leading bacterial gastroenteritis pathogens. Infections are largely underreported, and the burden of outbreaks may be underestimated. Current strategies of testing as few as one isolate per sample can affect attribution of cases to epidemiologically important sources with high Campylobacter diversity, such as chicken meat. Multiple culture method combinations were utilized to recover and sequence Campylobacter from 45 retail chicken samples purchased across Norwich, UK, selecting up to 48 isolates per sample. Simulations based on resampling were used to assess the impact of Campylobacter sequence type (ST) diversity on outbreak detection. Campylobacter was recovered from 39 samples (87%), although only one sample was positive through all broth, temperature, and plate combinations. Three species were identified (Campylobacter jejuni, Campylobacter coli, and Campylobacter lari), and 33% of samples contained two species. Positive samples contained 1–8 STs. Simulation revealed that up to 87 isolates per sample would be required to detect 95% of the observed ST diversity, and 26 isolates would be required for the average probability of detecting a random theoretical outbreak ST to reach 95%. An optimized culture approach and selecting multiple isolates per sample are essential for more complete Campylobacter recovery to support outbreak investigation and source attribution.
Integrons are important genetic elements that allow easy acquisition and dissemination of antimicrobial resistance genes. Studies reporting occurrence of integrons in Staphylococcus aureus (S. aureus) isolated from bovine mastitis in large dairy farms across China are scarce. The aim of this study was to investigate the occurrence of class 1 integrons (intI1), antimicrobial resistance (AMR) and associated genes in S. aureus isolated from bovine mastitis and their associations. Minimum inhibitory concentrations (MICs) were determined to evaluate the AMR phenotypes, whereas PCR was carried out to assess the occurrence of AMR genes and intI1. In addition, index cluster analysis was used to estimate associations between AMR phenotype, genotype and intI1 in 103 isolates. Overall, 83% of S. aureus were intI1-positive and 5 types of gene cassettes were detected. Susceptibility against single antimicrobial agents ranged from 0% (erythromycin), 12% (ampicillin) and 16% (penicillin G) to 96% (gentamicin). Most isolates (64%) were intermediate-resistant against erythromycin, whereas resistance against ceftriaxone (22%), clindamycin (4%), cefotaxime (2%), tetracycline (1%) and ciprofloxacin (1%) were relatively uncommon. The predominant resistant gene was blaZ gene (n = 88, 85%) followed by tetD gene (n = 85, 83%). With an estimated prevalence of 12% of the mecA gene, methicillin-resistant S. aureus isolates had higher MIC50 and MIC90 for majority of antimicrobials than methicillin-susceptible S. aureus isolates. Presence of the ermC gene was associated with erythromycin resistance. Ampicillin, erythromycin and penicillin G resistance were associated with intI1. The data presented in our study indicated that class 1 integron-mediated resistance possibly plays an important role in dissemination of AMR in S. aureus isolated from bovine mastitis.
In this research communication we investigate the prevalence and antimicrobial susceptibility of S. aureus harboring virulent genes responsible for mastitis in cattle of Punjab, Pakistan. A total of 690 milk samples were collected from commercial dairy farms for analysis of the prevalence of subclinical and clinical mastitis and isolation of S. aureus. Virulence ability and methicillin resistance in S. aureus (MRSA) was determined by targeting the pvl (the gene for Panton–Valentine leukocidin) and mecA genes, respectively. A total of 175 S. aureus isolates exhibiting prevalence of pvl gene (6.28%) and mecA gene (22.28%) were determined. Antimicrobial susceptibility testing of pvl positive and negative MRSA against different classes of antibiotics revealed 100% resistance against β-lactams while 100% sensitivity towards tylosin and linezolid.
An antimicrobial is defined as a drug that kills, prevents, or inhibits the growth of any type of microorganism (1). These drugs originate from a variety of sources, including microorganisms, plants, animals, and can be semi-synthetic or synthetic. Antimicrobials can be antibacterial, antimycobacterial, antifungal, antiparasitic and antiviral (2). Strictly speaking, the term ‘antibiotic’ refers to an agent produced by a microorganism that kills another microorganism; it does not include synthetic substances (3). However, this specific meaning is often not emphasised in clinical practice. Therefore, in this book, the terms antibacterial and antibiotic will be used interchangeably.
Foodborne infections with antimicrobial-resistant Campylobacter spp. remain an important public health concern. Publicly available data collected by the National Antimicrobial Resistance Monitoring System for Enteric Bacteria related to antimicrobial resistance (AMR) in Campylobacter spp. isolated from broiler chickens and turkeys at the slaughterhouse level across the United States between 2013 and 2021 were analysed. A total of 1,899 chicken-origin (1,031 Campylobacter coli (C. coli) and 868 Campylobacter jejuni (C. jejuni)) and 798 turkey-origin (673 C. coli and 123 C. jejuni) isolates were assessed. Chicken isolates exhibited high resistance to tetracycline (43.65%), moderate resistance to ciprofloxacin (19.5%), and low resistance to clindamycin (4.32%) and azithromycin (3.84%). Turkey isolates exhibited very high resistance to tetracycline (69%) and high resistance to ciprofloxacin (39%). The probability of resistance to all tested antimicrobials, except for tetracycline, significantly decreased during the latter part of the study period. Turkey-origin Campylobacter isolates had higher odds of resistance to all antimicrobials than isolates from chickens. Compared to C. jejuni isolates, C. coli isolates had higher odds of resistance to all antimicrobials, except for ciprofloxacin. The study findings emphasize the need for poultry-type-specific strategies to address differences in AMR among Campylobacter isolates.
Antimicrobial resistance (AMR) is a growing One Health crisis that can be impacted by other challenges of sustainable development, such as climate change, but few interventions have been assessed with a systems-wide lens. The objectives of this study were to use a previously defined fuzzy cognitive map (FCM) of the Swedish One Health system to: 1) identify areas in the system to target interventions; and 2) test the potential ability and viability of interventions to reduce AMR under a changing climate. The FCM, based on participatory modelling workshops and literature scan, was used to assess the sustainability of eight interventions under potential climate change conditions. Network metrics were calculated to describe the system structure and identify highly impactful nodes. The network metrics identified high-leverage nodes including alternative productions systems and good farming practices. None of the scenarios evaluated were able to adequately reduce AMR within the system. Overall, fuzzy cognitive mapping provides an innovative way to analyse the AMR system, identify high-leverage interventions, and examine potential impact of interventions using a broader systems lens.
Antimicrobial resistance (AMR) remains a critical public health problem that pervades hospitals and health systems worldwide. The ongoing AMR crisis is not only concerning for patient care but also healthcare delivery and quality. This article outlines key components of the origins of AMR in the United States and how it presents across the American healthcare system. Numerous factors contributed to the crisis, including agricultural antibiotic use, wasteful prescribing practices in health care, conflicting behaviours among patients and clinicians, patient demand and satisfaction, and payment and reimbursement models that incentivize inappropriate antibiotic use. To combat AMR, clinicians, healthcare professionals, and legislators must continue to promote and implement innovative solutions, including antibiotic stewardship programmes (ASPs), hand hygiene protocols, ample supply of personal protective equipment (PPE), standardized treatment guidelines for antibiotic prescribing, clinician and patient educational programmes, and health policy initiatives. With the rising prevalence of multi-drug resistant bacterial infections, AMR must become a greater priority to policymakers and healthcare stakeholders.