Molecular characterization of predominant Streptococcus pneumoniae serotypes causing invasive infections in Canada:the SAVE study, 2011-15

Objectives: This study characterized the 11 most predominant serotypes of invasive Streptococcus pneumoniae infections collected by the annual SAVE study in Canada, between 2011 and 2015. Methods: A subset of the 11 most predominant serotypes (7F, 19A, 22F, 3, 12F, 11A, 9N, 8, 33F, 15A and 6C) collected by the SAVE study was analysed using PFGE and MLST, as well as PCR to identify pilus-encoding genes. WGS analyses were performed on a subset of the above isolates plus a random selection of background strains. Results: Of the predominant serotypes analysed, 7F, 33F and 19A were obtained more commonly from children 65 years of age. Pneumococcal pilus PI-1 was identified in antimicrobial-susceptible serotype 15A (61/212) and <10% of 6C isolates (16/188). PI-2 was found in serotype 7F (683/701) and two-thirds of 11A isolates (162/241). Only serotype 19A-ST320 possessed both pili. Molecular and phylogenetic analyses identified serotypes 19A, 15A, 6C, 9N and 33F as highly diverse, whereas 7F, 22F and 11A demonstrated clonality. Antimicrobial resistance determinants were common within diverse serotypes, and usually similar within a clonal complex. Conclusions: Despite successful use of conjugate vaccines, S. pneumoniae remains a highly diverse organism in Canada. Several predominant serotypes, both antimicrobial susceptible and MDR, have demonstrated rapid clonal expansion or an increase in diversity. As S. pneumoniae continues to evolve in Canada, WGS will be a necessary component in the ongoing surveillance of antimicrobial-resistant and expanding clones

Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis.

BACKGROUND: Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen-drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date. METHODS: We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen-drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). 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. We present final estimates aggregated to the global and regional level. FINDINGS: On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62-6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911-1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9-35·3), and lowest in Australasia, at 6·5 deaths (4·3-9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000-1 270 000) deaths attributable to AMR and 3·57 million (2·62-4·78) deaths associated with AMR in 2019. One pathogen-drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000-100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae. INTERPRETATION: To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen-drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat. 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 European region in 2019: a cross-country systematic analysis.

BACKGROUND: Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date. METHODS: We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries 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). Data were solicited from a wide array of international stakeholders; these included 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: We estimated 541 000 deaths (95% UI 370 000-763 000) associated with bacterial AMR and 133 000 deaths (90 100-188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000-333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900-185 000]) and respiratory infections (120 000 deaths [94 500-154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR. INTERPRETATION: The high levels of resistance for several important bacterial pathogens and pathogen-drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen-drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours. FUNDING: Bill &amp; Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund

Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods: We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. Findings: From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation: The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund.info:eu-repo/semantics/publishedVersio

A Public health action plan to combat antimicrobial resistance. Part 1. Domestic issues

Interagency Task Force on Antimicrobial Resistance.Title from caption (viewed on Jan. 26, 2006).The Task Force is co-chaired by the Centers for Disease Control and Prevention, Food and Drug Administration, and the National Institutes of Health. It also includes the Agency for Healthcare Research and Quality ... [et al.].Also available in print.Mode of access: Internet; PDF reader.Includes bibliographical references and index.Text (electronic publication

2011 progress towards implementation of a public health action plan to combat antimicrobial resistance

In 2001, the Task Force developed an initial Action Plan, outlining specific issues, goals, and actions important for addressing the problem of AR. This document, entitled A Public Health Action Plan to Combat Antimicrobial Resistance, Part I: Domestic Issues, reflected a broad- based consensus of participating federal agencies, which was reached with individual input from state and local health agencies, universities, professional societies, pharmaceutical companies, healthcare delivery organizations, agricultural producers, consumer groups, and other members of the public. Continued collaboration with these partners has been vital to achieving successful implementation of the Action Plan. The 2011 revision of the Action Plan was based in part on individual input obtained at a consultants' meeting held in Atlanta, Georgia, in December 2007. Present at the public meeting were consultants with wide-ranging expertise in areas such as human and veterinary medicine, pharmaceutical and diagnostics manufacturing, animal husbandry, clinical microbiology, epidemiology, infectious diseases and infection control, and state and local public health officials. The Action Plan includes action items organized into four focus areas: Surveillance, Prevention and Control, Research, and Product Development.Executive summary -- Introduction and overview -- The Focus Areas -- Focus Area I: Surveillance -- Focus Area II: Prevention and Control -- Focus Area III: Research -- Focus Area IV: Product Development -- Acronyms and abbreviationsInteragency Task Force on Antimicrobial Resistance ; co-chairs: Centers for Disease Control and Prevention, Food and Drug Administration.Title from caption (viewed on October 1, 2012).The Interagency Task Force on Antimicrobial Resistance (hereafter referred to as the Task Force) was created in 1999 to coordinate the activities of federal agencies in addressing antimicrobiala resistance (AR) in recognition of the increasing importance of AR as a public health threat. The Task Force is co-chaired by the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), and the National Institutes of Health (NIH) and also includes the Agency for Healthcare Research and Quality (AHRQ), the Centers for Medicare and Medicaid Services (CMS), the Department of Agriculture (USDA), the Department of Defense (DoD), the Department of Veterans Affairs (VA), the Environmental Protection Agency (EPA), the Health Resources and Services Administration (HRSA), the Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response (HHS/ASPR), and the Department of Health and Human Services Office of the Assistant Secretary for Health (HHS/OASH).Mode of access: Internet; PDF reader (Acrobat .pdf file: 459 KB, 69 p.).Text (electronic publication

NARMS

The National Antimicrobial Resistance Monitoring System (NARMS) for Enteric Bacteria is a collaboration among the Centers for Disease Control and Prevention (CDC), U.S. Food and Drug Administration's Center for Veterinary Medicine (FDA-CVM), and U.S. Department of Agriculture (USDA). The primary purpose of NARMS at CDC is to monitor antimicrobial resistance among foodborne enteric bacteria isolated from humans. Other components of the interagency NARMS program include surveillance for resistance in enteric bacterial pathogens isolated from foods, conducted by the FDA-CVM (http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/default.htm), and resistance in enteric pathogens isolated from animals, conducted by the USDA Agricultural Research Service (http://www.ars.usda.gov/main/site_main.htm?modecode=66-12-05-08). Many NARMS activities are conducted within the framework of CDC's Emerging Infections Program (EIP), Epidemiology and Laboratory Capacity (ELC) Program, and the Foodborne Diseases Active Surveillance Network (FoodNet). In addition to surveillance of resistance in enteric pathogens, the NARMS program at CDC also includes public health research into the mechanisms of resistance, education efforts to promote prudent use of antimicrobial agents, and studies of resistance in commensal organisms. Before NARMS was established, CDC monitored antimicrobial resistance in Salmonella, Shigella, and Campylobacter through periodic surveys of isolates from a panel of sentinel counties. NARMS at CDC began in 1996 with prospective monitoring of antimicrobial resistance among clinical non-typhoidal Salmonella and Escherichia coli O157 isolates in 14 sites. In 1997, testing of clinical Campylobacter isolates was initiated in the five sites participating in FoodNet. Testing of clinical Salmonella enterica serotype Typhi and Shigella isolates was added in 1999. Since 2003, all 50 states have been forwarding a representative sample of non-typhoidal Salmonella, Salmonella ser. Typhi, Shigella, and E. coli O157 isolates to NARMS for antimicrobial susceptibility testing, and 10 FoodNet states have been participating in Campylobacter surveillance. This annual report includes CDC's surveillance data for 2008 for non-typhoidal Salmonella, typhoidal Salmonella, Shigella, Campylobacter and E. coli O157 isolates. Data for earlier years are presented in tables and graphs when appropriate. Antimicrobial classes defined by Clinical and Laboratory Standards Institute (CLSI) are used in data presentation and analysis. CLSI classes constitute major classifications of antimicrobial agents, e.g., aminoglycosides and cephems. This report also includes the World Health Organization's categorization of antimicrobials of critical importance to human medicine. The table includes only antimicrobials that are tested in NARMS.List of tables -- List of figures -- List of boxes -- List of abbreviations and acronyms -- NARMS working group -- What is new in the NARMS report for 2008 -- Introduction -- WHO categorization of antimicrobial agents -- Summary of NARMS 2008 surveillance data -- Surveillance and laboratory testing methods -- Results -- References -- NARMS publications in 2008 -- Appendix A. Summary of Escherichia coli resistance surveillance pilot study, 2008C5215511-A.Includes bibliographical references (p. 65-66).CDC. National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS): Human Isolates Final Report, 2008. Atlanta, Georgia: U.S. Department of Health and Human Services, CDC, 2010