Antimicrobial-resistant ESKAPE ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens represent a global threat to human health. The acquisition of antimicrobial resistance genes by ESKAPE pathogens has reduced the treatment options for serious infections, increased the burden of disease, and increased death rates due to treatment failure and requires a coordinated global response for antimicrobial resistance surveillance. This looming health threat has restimulated interest in the development of new antimicrobial therapies, has demanded the need for better patient care, and has facilitated heightened governance over stewardship practices.

Antimicrobial resistance in ESKAPE pathogens

Objective:To describe common pathogens and antimicrobial resistance patterns for healthcare-associated infections (HAIs) among pediatric patients that occurred in 2015–2017 and were reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network (NHSN).Methods:Antimicrobial resistance data were analyzed for pathogens implicated in central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated pneumonias (VAPs), and surgical site infections (SSIs). This analysis was restricted to device-associated HAIs reported from pediatric patient care locations and SSIs among patients <18 years old. Percentages of pathogens with nonsusceptibility (%NS) to selected antimicrobials were calculated by HAI type, location type, and surgical category.Results:Overall, 2,545 facilities performed surveillance of pediatric HAIs in the NHSN during this period. Staphylococcus aureus (15%), Escherichia coli (12%), and coagulase-negative staphylococci (12%) were the 3 most commonly reported pathogens associated with pediatric HAIs. Pathogens and the %NS varied by HAI type, location type, and/or surgical category. Among CLABSIs, the %NS was generally lowest in neonatal intensive care units and highest in pediatric oncology units. Staphylococcus spp were particularly common among orthopedic, neurosurgical, and cardiac SSIs; however, E. coli was more common in abdominal SSIs. Overall, antimicrobial nonsusceptibility was less prevalent in pediatric HAIs than in adult HAIs.Conclusion:This report provides an updated national summary of pathogen distributions and antimicrobial resistance patterns among pediatric HAIs. These data highlight the need for continued antimicrobial resistance tracking among pediatric patients and should encourage the pediatric healthcare community to use such data when establishing policies for infection prevention and antimicrobial stewardship.

Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network, 2015–2017

Staphylococcus aureus is one of the most frequent worldwide causes of morbidity and mortality due to an infectious agent This pathogen can cause a wide variety of diseases, ranging from moderately

https://www.tandfonline.com/doi/pdf/10.1080/21505594.2021.1878688

Pathogenicity and virulence of Staphylococcus aureus.

Background
Resistance to all first-line antibiotics necessitates the use of less effective or more toxic “reserve” agents Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic

Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents.

Antibiotic resistance is undoubtedly one of the greatest challenges to global health, and the emergence of resistance has outpaced the development of new antibiotics. However, investments by the pharmaceutical industry and biotechnology companies for research into and development of new antibiotics are diminishing. The public health implications of a drying antibiotic pipeline are recognized by policymakers, regulators and many companies. In this Viewpoint article, seven experts discuss the challenges that are contributing to the decline in antibiotic drug discovery and development, and the national and international initiatives aimed at incentivizing research and the development of new antibiotics to improve the economic feasibility of antibiotic development. In this Viewpoint article, seven experts discuss the challenges that are contributing to the decline in antibiotic drug discovery and development, and the international and national initiatives aimed at incentivizing research and the development of new antibiotics to improve the economic feasibility of antibiotic development. Christine Ardal co-leads research and innovation in the European Union Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections. Previously she was the co-lead on incentives to stimulate antibacterial innovation for the European Union’s DRIVE-AB project. She is a senior adviser at the Norwegian Institute of Public Health, where her research and policy work focuses on medicine innovation, access and stewardship. Manica Balasegaram trained as a medical doctor at the University of Nottingham, United Kingdom, and from 2001 onwards worked as a doctor and researcher in several countries in sub-Saharan Africa and southern Asia with Medecins Sans Frontieres. In 2007, he joined the Drugs for Neglected Diseases initiative as Head of the Leishmaniasis Clinical Program before returning to Medecins Sans Frontieres as Executive Director of the Access Campaign. He joined the Global Antibiotic Research and Development Partnership in June 2016, and is a board member of the Medicines Patent Pool as well as FIND’s Scientific Advisory Committee. He is also the executive director of GARDP. Ramanan Laxminarayan is the founder and Director of the Center for Disease Dynamics, Economics & Policy in Washington, DC, United States, and a senior research scholar at Princeton University. He is a voting member of the US Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria. David McAdams is a game theorist and professor of economics in the Fuqua School of Business and Economics Department at Duke University, United States. His current research focuses on the economic epidemiology of information, with applications from antibiotic resistance to ‘fake news’. Kevin Outterson is a professor of law and N. Neal Pike Scholar in Health and Disability Law at Boston University, United States, and Executive Director of CARB-X. He has grappled for a dozen years with issues peculiar to antibiotic research and development, especially relating to intellectual property, reimbursement and business models. He now leads the world’s largest push incentive for antibacterial research and development, CARB-X, with a 5-year budget exceeding US$500 million. The views expressed herein are personal, and do not necessarily represent the views of CARB-X or any CARB-X funder. John H. Rex is a physician and drug developer with more than 30 years of development and policy experience focused on antimicrobial agents. He is currently Chief Medical Officer of F2G Ltd (an antifungal biotechnology company), an expert-in-residence for the Wellcome Trust and an operating partner with a venture capital group (Advent Life Sciences) and was (2015–2019) a voting member of the US Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria. He blogs regularly at http://amr.solutions/blog.html. Nithima Sumpradit is a pharmacist and lead coordinator for development and implementation of Thailand’s National Strategic Plan on Antimicrobial Resistance 2017–2021. She is also a programme manager of the Royal Thai Government–WHO Country Cooperation Strategy Programme on Antimicrobial Resistance.

Antibiotic development — economic, regulatory and societal challenges

Introduction
Staphylococcus aureus is one of the most common pathogens in health care facilities and in the community, and can cause invasive infections, sepsis, and death. Despite progress in preventing methicillin-resistant S. aureus (MRSA) infections in health care settings, assessment of the problem in both health care and community settings is needed. Further, the epidemiology of methicillin-susceptible S. aureus (MSSA) infections is not well described at the national level.

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Vital Signs: Epidemiology and Recent Trends in Methicillin-Resistant and in Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections — United States

BACKGROUND Approaches to controlling emerging antibiotic resistance in health care settings have evolved over time. When resistance to broad-spectrum antimicrobials mediated by extended-spectrum β-lactamases (ESBLs) arose in the 1980s, targeted interventions to slow spread were not widely promoted. However, when Enterobacteriaceae with carbapenemases that confer resistance to carbapenem antibiotics emerged, directed control efforts were recommended. These distinct approaches could have resulted in differences in spread of these two pathogens. CDC evaluated these possible changes along with initial findings of an enhanced antibiotic resistance detection and control strategy that builds on interventions developed to control carbapenem resistance. METHODS Infection data from the National Healthcare Safety Network from 2006-2015 were analyzed to calculate changes in the annual proportion of selected pathogens that were nonsusceptible to extended-spectrum cephalosporins (ESBL phenotype) or resistant to carbapenems (carbapenem-resistant Enterobacteriaceae [CRE]). Testing results for CRE and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are also reported. RESULTS The percentage of ESBL phenotype Enterobacteriaceae decreased by 2% per year (risk ratio [RR] = 0.98, p<0.001); by comparison, the CRE percentage decreased by 15% per year (RR = 0.85, p<0.01). From January to September 2017, carbapenemase testing was performed for 4,442 CRE and 1,334 CRPA isolates; 32% and 1.9%, respectively, were carbapenemase producers. In response, 1,489 screening tests were performed to identify asymptomatic carriers; 171 (11%) were positive. CONCLUSIONS The proportion of Enterobacteriaceae infections that were CRE remained lower and decreased more over time than the proportion that were ESBL phenotype. This difference might be explained by the more directed control efforts implemented to slow transmission of CRE than those applied for ESBL-producing strains. Increased detection and aggressive early response to emerging antibiotic resistance threats have the potential to slow further spread.

https://stacks.cdc.gov/view/cdc/52984/cdc_52984_DS1.pdf

Capers C

Papers

Vital Signs: Epidemiology and Recent Trends in Methicillin-Resistant and in Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections — United States

Vital Signs: Containment of Novel Multidrug-Resistant Organisms and Resistance Mechanisms — United States, 2006–2017