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.

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.

C.coli is a significant cause of foodborne gastroenteritis worldwide, with the majority of cases attributed to C.jejuni. Although most clinical laboratories do not typically conduct antimicrobial susceptibility testing for C.coli, the rise in resistant strains has underscored the necessity for such testing and epidemiological surveillance. The current study presents clinical isolate characteristics and demographics of 221 patients with C.coli (coli and jejuni) infections in Northern Israel, between 2015 and 2021. Clinical and demographic data were collected from patient medical records. Susceptibility to erythromycin, tetracycline, ciprofloxacin, and gentamicin was assessed using the standard E-test. No significant correlations were found between bacterial species and patient ethnicity, patient gender, or duration of hospitalization. In contrast, significant differences were found between infecting species and patient age and age subgroup (P < 0.001). Furthermore, erythromycin resistance was observed in only 0.5% of the study population, while resistance to ciprofloxacin, tetracycline, and gentamicin was observed in 95%, 93%, and 2.3% of the population, respectively. The presented study underscores the need for routine surveillance of C.coli antibiotic resistance.

Antimicrobial resistance (AMR) is a pressing global health issue with serious implications for health, food security, and livelihoods. Collective action, from local to global, that draws on the One Health (OH) approach to facilitate collaboration between the human, animal, and environmental sectors is required to inform initiatives to mitigate AMR. For AMR surveillance, this involves applying an intersectoral, multistakeholder perspective to guide the co-creation of knowledge and policy around the collection, analysis, and application of surveillance data to detect, monitor, and prevent AMR health threats. Currently, there is little available evidence on how to operationalize a OH approach to support integrated AMR surveillance systems, or on how the governance of such systems facilitates intersectoral action on AMR. We conducted a scoping review of the literature to identify the governance domains most relevant to applying the OH approach to the design and evaluation of AMR surveillance systems. We found that governance is a crucial component of the development of surveillance systems equipped to tackle complex, structural issues such as AMR. The governance domains identified include participation, coordination and collaboration, management, sustainability, accountability and transparency, and equity. These domains are relevant throughout all stages of policy design, implementation, and evaluation of AMR surveillance systems. Equity is both a domain and an essential component of the other domains. All the domains are interdependent and co-constitutive, so that progress in one domain can accelerate progress in another. The conceptual framework presented in this article can inform the design and evaluation of OH AMR governance systems and other complex health challenges that have similar barriers and facilitators to OH governance. The qualitative evaluation questions developed for each domain facilitate assessment of the breadth (the range of actors involved in governance) and depth (how meaningful their engagement is) for each domain relevant to OH governance. Finally, the prioritization of formal, sustainable, and democratic governance of AMR can help to facilitate achievement of the sustainable development goals (SDGs) and promote conservation of the use of antimicrobials for future generations.

The aim of this study was to compare the effects of feeding pasteurized waste milk or saleable milk to calves on weight, health and emergence of antimicrobial resistance in Escherichia coli strains isolated from those calves. An experimental study under field conditions on a commercial pasture-based Argentinian dairy farm was carried out. Forty Holstein calves were assigned randomly to either pasteurized waste milk (PWM) or non-pasteurized saleable milk (SM). The antimicrobial agents (AM) used on the farm, both to treat or prevent diseases, were recorded. The passive immunity level, calf live weight, AM presence in milk, clinical examination of calves, and E. coli isolation and identification, were performed. A total of 258 E. coli strains were isolated from fecal samples (132 isolates from SM calves and 126 from PWM calves at six sampling times). All E. coli isolated were used to perform AM susceptibility tests (disc diffusion and agar dilution). No differences were observed between groups in health parameters, average daily gain or prevalence of resistant E. coli strains to any AM evaluated throughout the study. Peaks of trimethoprim, sulfamethoxazole and enrofloxacin minimum inhibitory concentration (MIC) were observed at 30 d in E. coli from both groups of calves, whilst additional peaks to tetracyclin and ampicillin were observed only in SM calves. All MIC apart from gentamicin decreased at 75 and 90 d of age (during the weaning period). Gentamicin MIC behaved differently, having no peaks and increasing at 90 d only in PWM group. In conclusion, we found no evidence that emergence of antibiotic resistance is related to the consumption of pasteurized waste milk.

Enteric bacterial infections are common among people who travel internationally. During 2017–2020, the Centers for Disease Control and Prevention investigated 41 multistate outbreaks of nontyphoidal Salmonella and Shiga toxin-producing Escherichia coli linked to international travel. Resistance to one or more antimicrobial agents was detected in at least 10% of isolates in 16 of 30 (53%) nontyphoidal Salmonella outbreaks and 8 of 11 (73%) Shiga toxin-producing E. coli outbreaks evaluated by the National Antimicrobial Resistance Monitoring System. At least 10% of the isolates in 14 nontyphoidal Salmonella outbreaks conferred resistance to one or more of the clinically significant antimicrobials used in human medicine. This report describes the epidemiology and antimicrobial resistance patterns of these travel-associated multistate outbreaks. Investigating illnesses among returned travellers and collaboration with international partners could result in the implementation of public health interventions to improve hygiene practices and food safety standards and to prevent illness and spread of multidrug-resistant organisms domestically and internationally.

The resistance–nodulation–division efflux machinery confers antimicrobial resistance to Gram-negative bacteria by actively pumping antibiotics out of the cell. The protein complex is powered by proton motive force; however, the proton transfer mechanism itself and indeed even its stoichiometry is still unclear. Here we review computational studies from the last decade that focus on elucidating the number of protons transferred per conformational cycle of the pump. Given the difficulties in studying proton movement using even state-of-the-art structural biology methods, the contributions from computational studies have been invaluable from a mechanistic perspective.

Turkeys are important sources of antimicrobial-resistant Campylobacter. A total of 1063 isolates were obtained from 293 turkey flocks across Canada between 2016 and 2021 to evaluate their antimicrobial resistance (AMR) prevalence, patterns, distribution, and association with antimicrobial use (AMU). A high proportion of C. jejuni and C. coli isolates were resistant to tetracyclines and fluoroquinolones, despite the very low use of these drugs. C. jejuni isolates had a higher probability of being resistant to tetracyclines than C. coli isolates. The chance of C. jejuni isolates being resistant to fluoroquinolones, macrolides, and lincosamides was lower compared to C. coli. Isolates from the western region had a higher probability of being resistant to fluoroquinolones than isolates from Ontario. Isolates from Ontario had higher odds of being resistant to tetracyclines than isolates from Quebec. No associations were noted between the resistance and use of the same antimicrobial, but the use of certain antimicrobial classes may have played a role in the maintenance of resistance in Campylobacter (fluoroquinolone resistance – bacitracin and streptogramin use, tetracycline resistance – flavophospholipids and streptogramins use, macrolide resistance – flavophospholipid use). Low-level multidrug-resistant Campylobacter was observed indicating a stable AMR in turkeys. This study provided insights aiding future AMU and AMR surveillance.