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

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

Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: trends in pyrethroid resistance during a WHO-coordinated multi-country prospective study.

BACKGROUND: Increasing pyrethroid resistance has been an undesirable correlate of the rapid increase in coverage of insecticide-treated nets (ITNs) since 2000. Whilst monitoring of resistance levels has increased markedly over this period, longitudinal monitoring is still lacking, meaning the temporal and spatial dynamics of phenotypic resistance in the context of increasing ITN coverage are unclear. METHODS: As part of a large WHO-co-ordinated epidemiological study investigating the impact of resistance on malaria infection, longitudinal monitoring of phenotypic resistance to pyrethroids was undertaken in 290 clusters across Benin, Cameroon, India, Kenya and Sudan. Mortality in response to pyrethroids in the major anopheline vectors in each location was recorded during consecutive years using standard WHO test procedures. Trends in mosquito mortality were examined using generalised linear mixed-effect models. RESULTS: Insecticide resistance (using the WHO definition of mortality < 90%) was detected in clusters in all countries across the study period. The highest mosquito mortality (lowest resistance frequency) was consistently reported from India, in an area where ITNs had only recently been introduced. Substantial temporal and spatial variation was evident in mortality measures in all countries. Overall, a trend of decreasing mosquito mortality (increasing resistance frequency) was recorded (Odds Ratio per year: 0.79 per year (95% CI: 0.79-0.81, P < 0.001). There was also evidence that higher net usage was associated with lower mosquito mortality in some countries. DISCUSSION: Pyrethroid resistance increased over the study duration in four out of five countries. Insecticide-based vector control may be compromised as a result of ever higher resistance frequencies

Antimicrobial susceptibility testing of invasive isolates of Streptococcus pneumoniae from Canadian patients:the SAVE study, 2011-15

Objectives: To assess antimicrobial susceptibility for 14 agents tested against 6001 invasive isolates of Streptococcus pneumoniae cultured from invasive patient samples from 2011 to 2015 as a part of the annual SAVE study. Methods: Isolates of S. pneumoniae were tested using the standard CLSI broth microdilution method (M07-A10, 2015) with MICs interpreted by CLSI M100 27th Edition (2017) MIC breakpoints. Results: From 2011 to 2015, small but significant increases (P ≤ 0.05) in the percentage susceptibility for penicillin (interpreted by all three CLSI MIC breakpoint criteria) (increase of 1.7%-3.2%), clindamycin (3.1%) and ceftriaxone (interpreted by non-meningitis and meningitis CLSI MIC breakpoint criteria) (1.1%-1.5%) were observed. Susceptibility rates for clarithromycin and other commonly tested antimicrobial agents remained unchanged (P > 0.05) over the 5 year period. Isolates with an MDR phenotype (resistance to three or more antimicrobial agent classes) decreased significantly (P  0.05) with patient gender (exception: clarithromycin) but were associated (P ≤ 0.05) with patient age (chloramphenicol and clindamycin) or specimen source (penicillin, doxycycline, trimethoprim/sulfamethoxazole and clindamycin), as well as geographic location in Canada and concurrent resistance to penicillin or clarithromycin. Conclusions: The in vitro susceptibility of invasive isolates of S. pneumoniae in Canada to penicillin, clindamycin and ceftriaxone increased from 2011 to 2015, coincident with a significant decrease in MDR phenotypes