The Burden of antimicrobial Resistance in the americas in 2019: a Cross-Country Systematic analysis

BACKGROUND: Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive-despite the region\u27s long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat. METHODS: We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature reviews, and other sources, and applied predictive statistical modelling to produce estimates of AMR burden for all countries in the Americas. Five broad components were the backbone of our approach: the number of deaths where infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of pathogens resistant to an antibiotic class, and the excess risk of mortality (or duration of an infection) associated with this resistance. We then used these components to estimate the disease burden by applying two counterfactual scenarios: deaths attributable to AMR (compared to an alternative scenario where resistant infections are replaced with susceptible ones), and deaths associated with AMR (compared to an alternative scenario where resistant infections would not occur at all). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. FINDINGS: We estimated 569,000 deaths (95% UI 406,000-771,000) associated with bacterial AMR and 141,000 deaths (99,900-196,000) attributable to bacterial AMR among the 35 countries in the WHO Region of the Americas in 2019. Lower respiratory and thorax infections, as a syndrome, were responsible for the largest fatal burden of AMR in the region, with 189,000 deaths (149,000-241,000) associated with resistance, followed by bloodstream infections (169,000 deaths [94,200-278,000]) and peritoneal/intra-abdominal infections (118,000 deaths [78,600-168,000]). The six leading pathogens (by order of number of deaths associated with resistance) were INTERPRETATION: Given the burden across different countries, infectious syndromes, and pathogen-drug combinations, AMR represents a substantial health threat in the Americas. Countries with low access to antibiotics and basic health-care services often face the largest age-standardised mortality rates associated with and attributable to AMR in the region, implicating specific policy interventions. Evidence from this study can guide mitigation efforts that are tailored to the needs of each country in the region while informing decisions regarding funding and resource allocation. Multisectoral and joint cooperative efforts among countries will be a key to success in tackling AMR in the Americas. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund

The burden of bacterial antimicrobial resistance in the WHO African region in 2019: a cross-country systematic analysis

Background A critical and persistent challenge to global health and modern health care is the threat of antimicrobial resistance (AMR). Previous studies have reported a disproportionate burden of AMR in low-income and middle-income countries, but there remains an urgent need for more in-depth analyses across Africa. This study presents one of the most comprehensive sets of regional and country-level estimates of bacterial AMR burden in the WHO African region to date. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for countries in the WHO African region in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). We obtained data from research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings In the WHO African region in 2019, there were an estimated 1·05 million deaths (95% UI 829 000–1 316 000) associated with bacterial AMR and 250 000 deaths (192 000–325 000) attributable to bacterial AMR. The largest fatal AMR burden was attributed to lower respiratory and thorax infections (119 000 deaths [92 000–151 000], or 48% of all estimated bacterial pathogen AMR deaths), bloodstream infections (56 000 deaths [37 000–82 000], or 22%), intra-abdominal infections (26 000 deaths [17 000–39 000], or 10%), and tuberculosis (18 000 deaths [3850–39 000], or 7%). Seven leading pathogens were collectively responsible for 821 000 deaths (636 000–1 051 000) associated with resistance in this region, with four pathogens exceeding 100 000 deaths each: Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. Third-generation cephalosporin-resistant K pneumoniae and meticillin-resistant S aureus were shown to be the leading pathogen–drug combinations in 25 and 16 countries, respectively (53% and 34% of the whole region, comprising 47 countries) for deaths attributable to AMR. Interpretation This study reveals a high level of AMR burden for several bacterial pathogens and pathogen–drug combinations in the WHO African region. The high mortality rates associated with these pathogens demonstrate an urgent need to address the burden of AMR in Africa. These estimates also show that quality and access to health care and safe water and sanitation are correlated with AMR mortality, with a higher fatal burden found in lower resource settings. Our cross-country analyses within this region can help local governments to leverage domestic and global funding to create stewardship policies that target the leading pathogen–drug combinations. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund

An Interprofessional Curriculum on Antimicrobial Stewardship Improves Knowledge and Attitudes Toward Appropriate Antimicrobial Use and Collaboration.

BackgroundInappropriate antimicrobial use can threaten patient safety and is the focus of collaborative physician and pharmacist antimicrobial stewardship teams. However, antimicrobial stewardship is not comprehensively taught in medical or pharmacy school curricula. Addressing this deficiency can teach an important concept as well as model interprofessional healthcare.MethodsWe created an antimicrobial stewardship curriculum consisting of an online learning module and workshop session that combined medical and pharmacy students, with faculty from both professions. Learners worked through interactive, branched-logic clinical cases relating to appropriate antimicrobial use. We surveyed participants before and after the curriculum using validated questions to assess knowledge and attitudes regarding antimicrobial stewardship and interprofessional collaboration. Results were analyzed using paired χ2 and t tests and mixed-effects logistic regression.ResultsAnalysis was performed with the 745 students (425 medical students, 320 pharmacy students) who completed both pre- and postcurriculum surveys over 3 years. After completing the curriculum, significantly more students perceived that they were able to describe the role of each profession in appropriate antimicrobial use (34% vs 82%, P < .001), communicate in a manner that engaged the interprofessional team (75% vs 94%, P < .001), and describe collaborative approaches to appropriate antimicrobial use (49% vs 92%, P < .001). Student favorability ratings were high for the online learning module (85%) and small group workshop (93%).ConclusionsA curriculum on antimicrobial stewardship consisting of independent learning and an interprofessional workshop significantly increased knowledge and attitudes towards collaborative antimicrobial stewardship among preclinical medical and pharmacy students

Antimicrobial peptides: agents of border protection for companion animals.

Over the past 20 years, there have been significant inroads into understanding the roles of antimicrobial peptides in homeostatic functions and their involvement in disease pathogenesis. In addition to direct antimicrobial activity, these peptides participate in many cellular functions, including chemotaxis, wound healing and even determination of canine coat colour. Various biological and genetic approaches have helped to elucidate the role of antimicrobial peptides with respect to innate immunity and host defense. Associations of antimicrobial peptides with various skin diseases, including psoriasis, rosacea and atopic dermatitis, have been documented in humans. In the longer term, therapeutic modulation of antimicrobial peptide expression may provide effective new treatments for disease. This review highlights current knowledge about antimicrobial peptides of the skin and circulating leukocytes, with particular focus on relevance to physiology and disease in companion animals

Multidrug-resistant Escherichia coli, Klebsiella pneumoniae and Staphylococcus spp. in houseflies and blowflies from farms and their environmental settings

Background: Antimicrobial resistance is rising globally at an alarming rate. While multiple active surveillance programs have been established to monitor the antimicrobial resistance, studies on the environmental link to antimicrobial spread are lacking. Methods: A total of 493 flies were trapped from a dairy unit, a dog kennel, a poultry farm, a beef cattle unit, an urban trash facility and an urban downtown area to isolate Escherichia coli, Klebsiella pneumoniae and Staphylococcus spp. for antimicrobial susceptibility testing and molecular characterization. Results: E. coli, K. pneumoniae and coagulase-negative Staphylococcus were recovered from 43.9%, 15.5% and 66.2% of the houseflies, and 26.0%, 19.2%, 37.0% of the blowflies, respectively. In total, 35.3% of flies were found to harbor antimicrobial-resistant bacteria and 9.0% contained multidrug-resistant isolates. Three Staphylococcus aureus isolates were recovered from blowflies while three extended spectrum beta lactamase (ESBL)-carrying E. coli and one ESBL-carrying K. pneumoniae were isolated from houseflies. Whole genome sequencing identified the antimicrobial resistance genes bla(CMY-2) and bla(CTXM-1) as ESBLs. Conclusion: Taken together, our data indicate that flies can be used as indicators for environmental contamination of antimicrobial resistance. More extensive studies are warranted to explore the sentinel role of flies for antimicrobial resistance

Antimicrobial stewardship practices in Virginia

The Society of Healthcare Epidemiology of America, the Centers for Disease Control and Prevention, and the President\u27s Council of Advisors on Science and Technology recognize the need to combat antimicrobial resistance through the promotion of antimicrobial stewardship programs. Health care facilities in Virginia were surveyed using a 23-item survey focused on facility characteristics and antimicrobial stewardship strategies. Antimicrobial stewardship activities were highly variable and many are missing key personnel and resources

Triple-targeting Gram-negative selective antimicrobial peptides capable of disrupting the cell membrane and lipid A biosynthesis

Early lipid A biosynthesis is a potential antimicrobial target as this is an essential component of lipid A producing Gram-negative bacteria. Herein, we introduce a potent and highly synergistic Gram-negative selective triple-targeting antimicrobial peptide. The peptide contains a dual lipid A biosynthesis inhibiting sequence and an antimicrobial sequence

ENHANCED METHOD FOR AMPLIFYING ANTIMICROBIAL ACTIVITY OF LACTOPEROXIDASE SYSTEM IN MILK AND DERIVED PRODUCTS BY CARROT EXTRACT AND BETA CAROTENE

OSCN–  has  been  known  and  well  documented  as  natural  antimicrobial  agent    generated  from the  lactoperoxidase  system (LPOS)  but  the  antimicrobial  activity  exerted  from  this  system  is  too  low  for  certain  food  such  as  milk  and  derived products (up to 1.2 log CFU/ml) resulting in the restriction on industrial  development  of  LPOS.  Our  previous  study  concluded  that  involvement  of  carrot  extract and beta carotene in LPOS significantly boosted the antimicrobial activity  (up  to  6  log  CFU/ml)  against  S.  enteritidis.  This  finding  should  be  continued  to  the  application  on  food.  Since  we  found  that  LPOS  generates  low  antimicrobial  activity  on  milk  and  derived  product,  our  research  will  be  conducted  on  the  application  of  LPOS  plus  carrot  extract  and  beta  carotene  on  milk  and  derived  product.  Because  the  high  antimicrobial  activity  is  needed  for  industrial  purposes,  this  research  may  open  the  way  for  industrial  development  of  natural  antimicrobial agent from LPOS.  This research will be conducted in three steps of experiment: (1) ensuring  the  incredible  antimicrobial  activity  of  LPOS  plus  carrot  extract  and  beta  carotene  against  three  poisonous  tropical bacteria:  C. jejuni,  S. enteritidis,  and E.  coli,  (2)  utilization  of  LPOS  plus  carrot  extract  and  beta  carotene  in  milk:  full  cream and skimmed milk, and (3) utilization of LPOS plus carrot extract and beta  carotene  in  milk  derived  product:  yogurt  and  tropical  fruity  milk.  The  purification  of  LPO  from  bovine  milk,  the  complimentary  data  analysis  for  generation  of  LPOS  antimicrobial  activity  by  the  addition  of  carrot  extract  and  beta  carotene  will  be  conducted  in  Japan  and  for  the  application  in  tropical  poisonous  bacteria,  milk,  and  milk  derived  product  will  be  conducted  in  Indonesia.  The  outcomes  of  this  research  from  three  step  of  research  are  three  international  publications  at  international‐scopus‐indexed‐journals  :  International Journal of  Dairy Science and  one  of  patent:  “enhanced  method  for  improvement of LPOS antimicrobial activity by involvement of carrot extract and  beta carotene in milk and derived product”.     Keywords:  Lactoperoxidase,  antimicrobial  activity,  carrot  extract,  beta  carotene,  milk, derived products

Development and application of an antibiotic spectrum index for benchmarking antibiotic selection patterns across hospitals

Standard metrics for antimicrobial use consider volume but not spectrum of antimicrobial prescribing. We developed an antibiotic spectrum index (ASI) to classify commonly used antibiotics based on activity against important pathogens. The application of this index to hospital antibiotic use reveals how this tool enhances current antimicrobial stewardship metrics.Infect Control Hosp Epidemiol 2017;38:993–997</jats:p