Ensuring progress on sustainable access to effective antibiotics at the 2024 UN General Assembly: a target-based approach.

Rising antimicrobial resistance (AMR) is a global health crisis for countries of all economic levels, alongside the broader challenge of access to antibiotics. As a result, development goals for child survival, healthy ageing, poverty reduction, and food security are at risk. Preserving antimicrobial effectiveness, a global public good, requires political will, targets, accountability frameworks, and funding. The upcoming second high-level meeting on AMR at the UN General Assembly (UNGA) in September, 2024, is evidence of political interest in addressing the problem of AMR, but action on targets, accountability, and funding, absent from the 2016 UNGA resolution, is needed. We propose ambitious yet achievable global targets for 2030 (relative to a prepandemic 2019 baseline): a 10% reduction in mortality from AMR; a 20% reduction in inappropriate human antibiotic use; and a 30% reduction in inappropriate animal antibiotic use. Given national variation in current levels of antibiotic use, these goals (termed the 10-20-30 by 2030) should be met within a framework of universal access to effective antibiotics. The WHO Access, Watch, Reserve (AWARE) system can be used to define, monitor, and evaluate appropriate levels of antibiotic use and access. Some countries should increase access to narrow-spectrum, safe, and affordable (Access) antibiotics, whereas others should discourage the inappropriate use of broader-spectrum (Watch) and last-resort (Reserve) antibiotics; AWARE targets should use a risk-based, burden-adjusted approach. Improved infection prevention and control, access to clean water and sanitation, and vaccination coverage can offset the selection effects of increased antibiotic use in low-income settings. To ensure accountability and global scientific guidance and consensus, we call for the establishment of the Independent Panel on Antimicrobial Access and Resistance and the support of leaders from low-income and middle-income countries.

Highly pathogenic avian influenza: Unprecedented outbreaks in Canadian wildlife and domestic poultry.

Canada experienced a wave of HPAI H5N1 outbreaks in the spring of 2022 with millions of wild and farmed birds being infected. Seabird mortalities in Canada have been particularly severe on the Atlantic Coast over the summer of 2022. Over 7 million birds have been culled in Canada, and outbreaks continue to profoundly affect commercial bird farms across the world. This new H5N1 virus can and has infected multiple mammalian species, including skunks, foxes, bears, mink, seals, porpoises, sea lions, and dolphins. Viruses with mammalian adaptations such as the mutations PB2-E627K, E627V, and D701N were found in the brain of various carnivores in Europe and Canada. To date this specific clade of H5N1 virus has been identified in less than 10 humans. At the ground level, awareness should be raised among frontline practitioners most likely to encounter patients with HPAI.

Le Canada a vécu un vague d'éclosions de grippe aviaire de souche H5N1 hautement pathogène au printemps 2022 lorsque des millions d'oiseaux sauvages et d'oiseaux d'élevage ont été infectés. La mortalité des oiseaux marins au Canada a été particulièrement marquée sur la côte Atlantique pendant l'été 2022. Plus de sept millions d'oiseaux ont été abattus au Canada, et les éclosions continuent de nuire profondément aux élevages commerciaux d'oiseaux dans le monde. Ce nouveau virus H5N1 peut infecter de multiples espèces de mammifères, y compris des mouffettes, des renards, des ours, des visons, des phoques, des marsouins, des otaries et des dauphins. Les virus adaptés aux mammifères et porteurs des mutations PB2-E627K, E627V et D701N, ont été observés dans le cerveau de divers carnivores de l'Europe et du Canada. Jusqu'à présent, ce clade du virus H5N1 a été dépisté chez moins de dix humains. Sur le terrain, il est important de sensibiliser les praticiens de première ligne qui sont plus susceptibles de voir des patients atteints de la grippe aviaire de souche hautement pathogène.

The effects of ambient temperature exposure on feline fecal metabolome.

Introduction: The fecal metabolome provides insight into overall gastrointestinal and microbial health. Methods for fecal sample storage in metabolomics research vary, however, making comparisons within current literature difficult. This study investigated the effect of ambient temperature exposure on microbial-derived metabolites of feline fecal samples. Methods: Fecal samples were collected from 11 healthy cats from a local boarding facility. Samples were manually homogenized and aliquoted. The first aliquot was frozen at -80°C within 1 hour of defecation, and remaining samples were exposed to ambient temperature for 2, 4, 6, 8, 12, and 24 h prior to freezing at -80°C. Fecal metabolites were quantified using 1H NMR spectroscopy. Fifty metabolites were grouped into six categories (27 amino acids, 8 fatty acids, 5 sugars, 3 alcohols, 2 nitrogenous bases, 5 miscellaneous). Results: Concentrations of 20 out of 50 metabolites significantly differed due to ambient temperature exposure (7 amino acids, 6 fatty acids, 2 alcohols, 1 nitrogenous base, 4 miscellaneous). The earliest detected changes occurred 6 h post-defecation for cadaverine and fumaric acid. Discussion: This study shows ambient temperature exposure alters the composition of the feline fecal metabolome, but short-term (up to 4 h) exposure prior to storage in the freezer seems to be acceptable.

Effect of dietary iron supplementation on the equine fecal microbiome.

Iron is an essential element for all living organisms, including bacteria, as several virulence factors and replication components are influenced by iron concentration. The objective of this study was to determine whether the composition and diversity of the fecal microbiota of adult horses are affected by supplemental dietary iron. Ten clinically healthy horses were randomly divided into a control and an iron-supplemented group (n = 5). The treated group was supplemented with oral ferrous sulphate monohydrate (720 ppm of iron), whereas the control group received 320 ppm of iron daily for 15 d. Fecal samples were collected before and 5, 10, 15, and 30 d after supplementation and frozen at -80°C. DNA was sequenced using an Illumina MiSeq platform and data were analyzed using the software Mothur and linear discriminant analysis (LDA) effect size (LEfSe). Iron supplementation caused no change in the overall composition of the fecal microbiota, but some minor changes were observed in the low-abundant bacteria, as well as an increased alpha diversity after 15 d of supplementation. Significant differences in community composition of the fecal microbiota over time were observed in both groups, highlighting the importance of a control group, as there are variables that cannot be controlled in microbiome studies.

Le fer est un élément essentiel pour tous les organismes vivants, y compris les bactéries, car plusieurs facteurs de virulence et composants de réplication sont influencés par la concentration en fer. L'objectif de cette étude était de déterminer si la composition et la diversité du microbiote fécal des chevaux adultes sont affectées par la supplémentation en fer alimentaire. Dix chevaux cliniquement sains ont été divisés au hasard en un groupe témoin et un groupe supplémenté en fer, n = 5 par groupe. Le groupe traité a reçu un supplément oral de sulfate ferreux monohydraté (720 ppm de fer) et le groupe témoin a reçu 320 ppm de fer par jour pendant 15 jours. Des échantillons fécaux ont été prélevés avant la supplémentation et 5, 10, 15 et 30 jours après la supplémentation puis congelés à −80 °C. L'ADN a été séquencé à l'aide de la plateforme Illumina MiSeq et les données ont été analysées à l'aide des logiciels Mothur et analyse de la fonction discriminante linéaire taille de l'effet LefSe. La supplémentation en fer n'a provoqué aucun changement dans la composition du microbiote fécal, mais certains changements ont été observés chez les bactéries peu abondantes, ainsi qu'une augmentation de la diversité alpha après 15 jours de supplémentation. Au fil du temps, des différences significatives dans la composition de la communauté bactérienne ont été observées dans les deux groupes, soulignant l'importance d'un groupe témoin, car il existe des variables qui ne peuvent être contrôlées dans les études sur le microbiome.(Traduit par les auteurs).

Spatial patterns of Borrelia burgdorferi, Borrelia miyamotoi and Anaplasma phagocytophilum detected in Ixodes spp. ticks from Canadian companion animals, 2019-2020.

Increasing temperatures due to climate change have contributed to a northward range expansion of Ixodes scapularis ticks in Canada. These ticks harbour pathogens of public and animal health significance, including Borrelia burgdorferi and Anaplasma phagocytophilum, which cause Lyme disease and anaplasmosis, respectively, in humans, dogs and horses, and Borrelia miyamotoi, which causes a flu-like relapsing fever in humans. To address the risks associated with these vector-borne zoonotic diseases, continuous tick surveillance is advised. This study examined spatial patterns of B. burgdorferi, B. miyamotoi and A. phagocytophilum from ticks submitted through a national study on ticks of companion animals. From 1 April 2019 to 31 March 2020, we received a total of 1541 eligible submissions from 94 veterinary clinics across Canada. Individual and pooled samples of a maximum of either 5 I. scapularis, I. pacificus or I. angustus samples from the same animal and of the same life stage were screened using real-time PCR targeting genes 23S rRNA for Borrelia spp. and msp2 for A. phagocytophilum. Confirmatory testing was conducted on all 23S rRNA positive samples using a duplex assay for ospA and flaB to differentiate B. burgdorferi and B. miyamotoi, respectively. Prevalence estimates were highest (>20%) for B. burgdorferi in southwestern Manitoba, eastern Ontario, southwestern Quebec, New Brunswick and Nova Scotia. Estimates of B. miyamotoi and A. phagocytophilum were much lower (<5%), except for higher A. phagocytophilum (>5%) estimates for southern Manitoba, eastern Ontario and Prince Edward Island. Findings from this study, combined with other surveillance approaches, can be used to guide veterinary and public health approaches for ticks and tick-borne diseases.

Evaluation of antimicrobial prescriptions in dogs with suspected bacterial urinary tract disease.

BACKGROUND: Antimicrobials are commonly used to treat urinary tract disease in dogs. Understanding antimicrobial use is a critical component of antimicrobial stewardship efforts. HYPOTHESIS/OBJECTIVES: To evaluate antimicrobial prescriptions for dogs diagnosed with acute cystitis, recurrent cystitis, and pyelonephritis. ANIMALS: Dogs prescribed antimicrobials for urinary tract disease at veterinary practices in the United States and Canada. MATERIALS AND METHODS: A retrospective review of antimicrobial prescriptions was performed. RESULTS: The main clinical concerns were sporadic bacterial cystitis (n = 6582), recurrent cystitis (n = 428), and pyelonephritis (n = 326). Amoxicillin/clavulanic acid (2702, 41%), cefpodoxime (1024, 16%), and amoxicillin (874, 13%) were most commonly prescribed for sporadic bacterial cystitis. The median prescribed duration was 12 days (range, 3-60 days; interquartile range [IQR], 4 days). Shorter durations were used in 2018 (median, 10 days; IQR, 4 days) compared to both 2016 and 2017 (both median, 14 days; IQR, 4 days; P ≤ .0002). Amoxicillin/clavulanic acid (146, 33%), marbofloxacin (95, 21%), and cefpodoxime (65, 14%) were most commonly used for recurrent cystitis; median duration of 14 days (range, 3-77 days; IQR, 10.5 days). Amoxicillin/clavulanic acid (86, 26%), marbofloxacin (56, 17%), and enrofloxacin (36, 11%) were most commonly prescribed for pyelonephritis; however, 93 (29%) dogs received drug combinations. The median duration of treatment was 14 days (range, 3-77 days; IQR, 11 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Decreases in duration and increased use of recommended first-line antimicrobials were encouraging. Common drug choices and durations should still be targets for antimicrobial stewardship programs that aim to optimize antimicrobial use, concurrently maximizing patient benefits while minimizing antimicrobial use and use of higher tier antimicrobials.

Clostridioides (Clostridium) difficile in neonatal foals and mares at a referral hospital.

BACKGROUND: Understanding the epidemiology of Clostridium difficile is important for the development and assessment of infection prevention and control practices, as well as surveillance methods and interpretation of diagnostic testing results. OBJECTIVE: Our objective was to longitudinally evaluate C. difficile shedding in neonatal foals and mares admitted to a referral hospital neonatal intensive care unit. ANIMALS: Foals admitted to a neonatal intensive care unit, along with their dams. METHODS: Rectal swabs were collected from mares and foals at admission, and then approximately every 3 days, when possible. Selective culture for C. difficile was performed and isolates were characterized by toxin gene PCR and ribotyping. RESULTS: Clostridium difficile was isolated from 103/409 (25%) samples; 65/208 (31%) from foals and 38/201 (19%) from mares. Cumulatively, C. difficile was isolated from at least 1 sample from 50/113 (44%) foals and 30/97 (31%) mares. No association was found between hospitalization day and isolation of C. difficile (P = .13). Twenty-three different ribotypes were identified, with ribotype 078 predominating. Fifteen foals had 2 positive samples during hospitalization. In only 6/15 (40%) foals was the same strain identified both times (5 ribotype 078 and 1 ribotype 012). CONCLUSIONS AND CLINICAL IMPORTANCE: Clostridium difficile is an important pathogen in adult horses and foals, and our findings highlight the complexity surrounding the epidemiology of this opportunistic pathogen. It can be found commonly, transiently, and cluster within a facility in the absence of identifiable disease occurrences or clusters.

Understanding the Intestinal Microbiome in Health and Disease.

This article provides readers with the basic concepts necessary to understand studies using recent molecular methods performed in intestinal microbiome assessment, with special emphasis on the high throughput sequencing. This review also summarizes the current knowledge on this topic and discusses future insights on the interaction between the intestinal microbiome and equine health.

Methicillin-resistant staphylococcal contamination of clothing worn by personnel in a veterinary teaching hospital.

OBJECTIVE: To determine the methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) contamination rate of white coats (WC) and surgical scrubs (SS) worn by personnel at the Ontario Veterinary College Health Sciences Centre (OVCHSC) and to identify risk factors associated with clothing contamination. STUDY DESIGN: Cross-sectional study. SAMPLE POPULATION: Personnel including clinical faculty, house officers, technicians, and veterinary students working at the OVCHSC. METHODS: Electrostatic cloths were used to sample WC and SS of hospital personnel. Samples were tested for MRSA and MRSP and isolates were typed. Participants completed a self-administered questionnaire and data was evaluated for risk factors. RESULTS: Of 114 specimens, MRS were isolated from 20 (17.5%), MRSA from 4 (3.5%), and MRSP from 16 (14.0%). Technicians were 9.5× (OR = 0.95, 95% CI: 1.2-∞, P = .03) more likely than students to have clothing contaminated with MRSA. No risk factors were identified for MRSP or for overall MRS contamination. CONCLUSIONS: Standard hospital clothing was found to have a high prevalence of MRS contamination in a veterinary teaching hospital and could be a source of hospital-acquired infections.

Characterization of the biofilm forming ability of Staphylococcus pseudintermedius from dogs.

BACKGROUND: Staphylococcus pseudintermedius is an opportunistic pathogen of dogs and has emerged as a leading cause of skin, wound and surgical site infections worldwide. Methicillin resistance is common and clinical infections as a result of methicillin-resistant S. pseudintermedius (MRSP) pose a clinical challenge. In other staphylococci, biofilm formation has been shown to be a virulence factor for infection, however, it has received little attention in S. pseudintermedius. The objectives of this study were to evaluate the biofilm forming ability of clinical isolates of S. pseudintermedius obtained from dogs using phenotypic and genotypic techniques. RESULTS: 96% (136/140) of S. pseudintermedius isolates were classified as strong or moderate biofilm producers, with the majority of isolates being able to produce biofilm. There was no difference in biofilm formation between MRSP and MSSP (p=0.8), amongst isolates from clinical infections compared with isolates obtained from colonized dogs (p=0.08), and between isolates from sequence type (ST) 71 and ST 68 (P=0.09). icaA was detected in 77.9% (109/140) of isolates and icaD was detected in 75.7% (106/140) of isolates. Scanning electron microscopic evaluation of S. pseudintermedius biofilm production revealed aggregates of cocci and irregularly produced extracellular polymeric matrix. CONCLUSION: The majority of S. pseudintermedius isolates evaluated in this study were able to produce biofilm and this may be an important virulence factor in the rapid emergence of this bacterium in veterinary hospitals worldwide. Further study into the mechanisms of biofilm formation by S. pseudintermedius is warranted.

Comparison of microbial populations in the small intestine, large intestine and feces of healthy horses using terminal restriction fragment length polymorphism.

BACKGROUND: The composition of the microbiota of the equine intestinal tract is complex. Determining whether the microbial composition of fecal samples is representative of proximal compartments of the digestive tract could greatly simplify future studies. The objectives of this study were to compare the microbial populations of the duodenum, ileum, cecum, colon and rectum (feces) within and between healthy horses, and to determine whether rectal (fecal) samples are representative of proximal segments of the gastrointestinal tract. Intestinal samples were collected from ten euthanized horses. 16S rRNA gene PCR-based TRFLP was used to investigate microbiota richness in various segments of the gastrointestinal tract, and dice similarity indices were calculated to compare the samples. RESULTS: Within horses large variations of microbial populations along the gastrointestinal tract were seen. The microbiota in rectal samples was only partially representative of other intestinal compartments. The highest similarity was obtained when feces were compared to the cecum. Large compartmental variations were also seen when microbial populations were compared between six horses with similar dietary and housing management. CONCLUSION: Rectal samples were not entirely representative of intestinal compartments in the small or large intestine. This should be taken into account when designing studies using fecal sampling to assess other intestinal compartments. Similarity between horses with similar dietary and husbandry management was also limited, suggesting that parts of the intestinal microbiota were unique to each animal in this study.

Presence and molecular characterization of Clostridium difficile and Clostridium perfringens in intestinal compartments of healthy horses.

BACKGROUND: Clostridium difficile and Clostridium perfringens are commonly associated with colitis in equids, but healthy carriers exist. Scarce information is available on the prevalence of Clostridium spp. in gastrointestinal compartments other than faeces in healthy horses, and it is unknown whether faecal samples are representative of proximal compartments. The objectives were to investigate the prevalence of C. difficile and C. perfringens in different intestinal compartments of healthy adult horses and to determine whether faecal samples are representative of colonization in proximal sites and overall carrier status. RESULTS: Toxigenic C. difficile was isolated from 14/135 (10.3%) samples from 8/15 (53.3%) horses. Between zero and three sites were positive per horse, and multiple sites were positive in four horses. Isolates were recovered from duodenum, jejunum, ileum, right dorsal colon, small colon and rectum. When multiple compartments were positive in a single horse, two different C. difficile ribotypes were always present. Clostridium perfringens Type A (CPE, ß2 toxin gene negative) was recovered from the left ventral colon of one horse (0.74%, 1/135 samples). Agreement between faeces and overall C. difficile carrier status was good. CONCLUSIONS: Clostridium difficile can be found in different compartments of the gastrointestinal tract of healthy horses, and multiple strains can be present in an individual horse. The prevalence of C. perfringens in healthy adult hoses was low, consistent with previous reports. Faecal samples were representative for presence of C. difficile in proximal compartments in 5/8 horses (63%) but were not representative for the specific strain.