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Klebsiella pneumoniae is a leading cause of antimicrobial-resistant (AMR) healthcare-associated infections, neonatal sepsis and community-acquired liver abscess, and is associated with chronic intestinal diseases. Its diversity and complex population structure pose challenges for analysis and interpretation of K. pneumoniae genome data. Here we introduce Kleborate, a tool for analysing genomes of K. pneumoniae and its associated species complex, which consolidates interrogation of key features of proven clinical importance. Kleborate provides a framework to support genomic surveillance and epidemiology in research, clinical and public health settings. To demonstrate its utility we apply Kleborate to analyse publicly available Klebsiella genomes, including clinical isolates from a pan-European study of carbapenemase-producing Klebsiella , highlighting global trends in AMR and virulence as examples of what could be achieved by applying this genomic framework within more systematic genomic surveillance efforts. We also demonstrate the application of Kleborate to detect and type K. pneumoniae from gut metagenomes. Klebsiella pneumoniae is a pathogen of increasing public health concern and antimicrobial resistance is becoming more prevalent. Here, the authors describe a K. pneumoniae genotyping tool, Kleborate, that can be used to identify lineages and detect antimicrobial resistance and virulence loci.

Estimating the burden of healthcare-associated infections (HAIs) compared to other communicable diseases is an ongoing challenge given the need for good quality data on the incidence of these infections and the involved comorbidities. Based on the methodology of the Burden of Communicable Diseases in Europe (BCoDE) project and 2011-2012 data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals, we estimated the burden of six common HAIs. The included HAIs were healthcare-associated pneumonia (HAP), healthcare-associated urinary tract infection (HA UTI), surgical site infection (SSI), healthcare-associated Clostridium difficile infection (HA CDI), healthcare-associated neonatal sepsis, and healthcare-associated primary bloodstream infection (HA primary BSI). The burden of these HAIs was measured in disability-adjusted life years (DALYs). Evidence relating to the disease progression pathway of each type of HAI was collected through systematic literature reviews, in order to estimate the risks attributable to HAIs. For each of the six HAIs, gender and age group prevalence from the ECDC PPS was converted into incidence rates by applying the Rhame and Sudderth formula. We adjusted for reduced life expectancy within the hospital population using three severity groups based on McCabe score data from the ECDC PPS. We estimated that 2,609,911 new cases of HAI occur every year in the European Union and European Economic Area (EU/EEA). The cumulative burden of the six HAIs was estimated at 501 DALYs per 100,000 general population each year in EU/EEA. HAP and HA primary BSI were associated with the highest burden and represented more than 60% of the total burden, with 169 and 145 DALYs per 100,000 total population, respectively. HA UTI, SSI, HA CDI, and HA primary BSI ranked as the third to sixth syndromes in terms of burden of disease. HAP and HA primary BSI were associated with the highest burden because of their high severity. The cumulative burden of the six HAIs was higher than the total burden of all other 32 communicable diseases included in the BCoDE 2009-2013 study. The main limitations of the study are the variability in the parameter estimates, in particular the disease models' case fatalities, and the use of the Rhame and Sudderth formula for estimating incident number of cases from prevalence data. We estimated the EU/EEA burden of HAIs in DALYs in 2011-2012 using a transparent and evidence-based approach that allows for combining estimates of morbidity and of mortality in order to compare with other diseases and to inform a comprehensive ranking suitable for prioritization. Our results highlight the high burden of HAIs and the need for increased efforts for their prevention and control. Furthermore, our model should allow for estimations of the potential benefit of preventive measures on the burden of HAIs in the EU/EEA.

Background Staphylococcus aureus is the most common organism responsible for orthopaedic surgical site infections (SSIs). Patients who are carriers for methicillin-sensitive S. aureus or methicillin-resistant S. aureus (MRSA) have a higher likelihood of having invasive S. aureus infections. Although some have advocated screening for S. aureus and decolonizing it is unclear whether these efforts reduce SSIs. Questions/purposes The purposes of this study were to determine (1) whether S. aureus screening and decolonization reduce SSIs in orthopaedic patients and (2) if implementing this protocol is cost-effective. Methods Studies for this systematic review were identified by searching PubMed, which includes MEDLINE (1946–present), EMBASE.com (1974–present), and the Cochrane Library’s (John Wiley & Sons) Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTAD), and the NHS Economic Evaluation Database (NHSEED). Comprehensive literature searches were developed using EMTREE, MeSH, and keywords for each of the search concepts of decolonization, MRSA, and orthopedics/orthopedic surgery. Studies published before 1968 were excluded. We analyzed 19 studies examining the ability of the decolonization protocol to reduce SSIs and 10 studies detailing the cost-effectiveness of S. aureus screening and decolonization. Results All 19 studies showed a reduction in SSIs or wound complications by instituting a S. aureus screening and decolonization protocol in elective orthopaedic (total joints, spine, and sports) and trauma patients. The S. aureus screening and decolonization protocol also saved costs in orthopaedic patients when comparing the costs of screening and decolonization with the reduction of SSIs. Conclusions Preoperative screening and decolonization of S. aureus in orthopaedic patients is a cost-effective means to reduce SSIs. Level of Evidence Level IV, systematic review of Level I–IV studies. See the Guidelines for Authors for a complete description of levels of evidence.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most successful modern pathogens. The same organism that lives as a commensal and is transmitted in both health-care and community settings is also a leading cause of bacteraemia, endocarditis, skin and soft tissue infections, bone and joint infections and hospital-acquired infections. Genetically diverse, the epidemiology of MRSA is primarily characterized by the serial emergence of epidemic strains. Although its incidence has recently declined in some regions, MRSA still poses a formidable clinical threat, with persistently high morbidity and mortality. Successful treatment remains challenging and requires the evaluation of both novel antimicrobials and adjunctive aspects of care, such as infectious disease consultation, echocardiography and source control. In this Review, we provide an overview of basic and clinical MRSA research and summarize the expansive body of literature on the epidemiology, transmission, genetic diversity, evolution, surveillance and treatment of MRSA.Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen both within hospitals and in the community. In this Review, Fowler and colleagues provide an overview of basic and clinical MRSA research and explore the epidemiology, transmission, genetic diversity, evolution, surveillance and treatment of MRSA.

Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.

Bacterial and fungal co-infection has been reported in patients with COVID-19, but there is limited experience on these infections in critically ill patients. The objective of this study was to assess the characteristics and ouctome of ICU-acquired infections in COVID-19 patients. We conducted a retrospective single-centre, case-control study including 140 patients with severe COVID-19 admitted to the ICU between March and May 2020. We evaluated the epidemiological, clinical, and microbiological features, and outcome of ICU-acquired infections. Fifty-seven patients (40.7%) developed a bacterial or fungal nosocomial infection during ICU stay. Infection occurred after a median of 9 days (IQR 5–11) of admission and was significantly associated with the APACHE II score (p = 0.02). There were 91 episodes of infection: primary (31%) and catheter-related (25%) bloodstream infections were the most frequent, followed by pneumonia (23%), tracheobronchitis (10%), and urinary tract infection (8%) that were produced by a wide spectrum of Gram-positive (55%) and Gram-negative bacteria (30%) as well as fungi (15%). In 60% of cases, infection was associated with septic shock and a significant increase in SOFA score. Overall ICU mortality was 36% (51/140). Infection was significantly associated with death (OR 2.7, 95% CI 1.2–5.9, p = 0.015) and a longer ICU stay (p < 0.001). Bacterial and fungal nosocomial infection is a common complication of ICU admission in patients with COVID-19. It usually presents as a severe form of infection, and it is associated with a high mortality and longer course of ICU stay.

Key Points Clostridium difficile infection (CDI) is a continually evolving global health-care problem Community-onset CDI is increasing and multiple potential reservoirs of infection exist including environmental sources, animals, asymptomatic patients and symptomatic patients Highly discriminatory typing techniques such as whole-genome sequencing and multi-locus variable-number tandem-repeat analysis offer the potential for illuminating previously under-recognized routes of C. difficile transmission The optimal approach to sampling and testing for CDI remains a contentious issue Multi-step algorithms are recommended to improve diagnostic sensitivity and specificity Clostridium difficile infection (CDI) is a global health-care problem and represents an important infection in both health-care facilities and the wider community. Here, the authors describe advances in understanding of CDI epidemiology, transmission and diagnosis, which are all key factors in the management of CDI. Clostridium difficile infection (CDI) continues to affect patients in hospitals and communities worldwide. The spectrum of clinical disease ranges from mild diarrhoea to toxic megacolon, colonic perforation and death. However, this bacterium might also be carried asymptomatically in the gut, potentially leading to 'silent' onward transmission. Modern technologies, such as whole-genome sequencing and multi-locus variable-number tandem-repeat analysis, are helping to track C. difficile transmission across health-care facilities, countries and continents, offering the potential to illuminate previously under-recognized sources of infection. These typing strategies have also demonstrated heterogeneity in terms of CDI incidence and strain types reflecting different stages of epidemic spread. However, comparison of CDI epidemiology, particularly between countries, is challenging due to wide-ranging approaches to sampling and testing. Diagnostic strategies for C. difficile are complicated both by the wide range of bacterial targets and tests available and the need to differentiate between toxin-producing and non-toxigenic strains. Multistep diagnostic algorithms have been recommended to improve sensitivity and specificity. In this Review, we describe the latest advances in the understanding of C. difficile epidemiology, transmission and diagnosis, and discuss the effect of these developments on the clinical management of CDI.

Introduction Acinetobacter baumannii constitutes a dreadful problem in many ICUs worldwide. The very limited therapeutic options available for these organisms are a matter of great concern. No specific guidelines exist addressing the prevention and management of A. baumannii infections in the critical care setting. Methods Clinical microbiologists, infectious disease specialists and intensive care physicians were invited by the Chair of the Infection Section of the ESICM to participate in a multidisciplinary expert panel. After the selection of clinically relevant questions, this document provides recommendations about the use of microbiological techniques for identification of A. baumannii in clinical laboratories, antibiotic therapy for severe infections and recommendations to control this pathogen in outbreaks and endemic situations. Evidence supporting each statement was graded according to the European Society of Clinical Microbiology and Infection Diseases (ESCMID) grading system. Results Empirical coverage of A. baumannii is recommended in severe infections (severe sepsis or septic shock) occurring during an A. baumannii outbreak, in an endemic setting, or in a previously colonized patient. For these cases, a polymyxin is suggested as part of the empirical treatment in cases of a high suspicion of a carbapenem-resistant (CR) A. baumannii strain. An institutional program including staff education, promotion of hand hygiene, strict contact and isolation precautions, environmental cleaning, targeted active surveillance, and antimicrobial stewardship should be instituted and maintained to combat outbreaks and endemic situations. Conclusions Specific recommendations about prevention and management of A. baumannii infections in the ICU were elaborated by this multidisciplinary panel. The paucity of randomized controlled trials is noteworthy, so these recommendations are mainly based on observational studies and pharmacodynamics modeling.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.

OBJECTIVE To describe antimicrobial resistance patterns for healthcare-associated infections (HAIs) that occurred in 2011-2014 and were reported to the Centers for Disease Control and Prevention's National Healthcare Safety Network. METHODS Data from central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonias, and surgical site infections were analyzed. These HAIs were reported from acute care hospitals, long-term acute care hospitals, and inpatient rehabilitation facilities. Pooled mean proportions of pathogens that tested resistant (or nonsusceptible) to selected antimicrobials were calculated by year and HAI type. RESULTS Overall, 4,515 hospitals reported that at least 1 HAI occurred in 2011-2014. There were 408,151 pathogens from 365,490 HAIs reported to the National Healthcare Safety Network, most of which were reported from acute care hospitals with greater than 200 beds. Fifteen pathogen groups accounted for 87% of reported pathogens; the most common included Escherichia coli (15%), Staphylococcus aureus (12%), Klebsiella species (8%), and coagulase-negative staphylococci (8%). In general, the proportion of isolates with common resistance phenotypes was higher among device-associated HAIs compared with surgical site infections. Although the percent resistance for most phenotypes was similar to earlier reports, an increase in the magnitude of the resistance percentages among E. coli pathogens was noted, especially related to fluoroquinolone resistance. CONCLUSION This report represents a national summary of antimicrobial resistance among select HAIs and phenotypes. The distribution of frequent pathogens and some resistance patterns appear to have changed from 2009-2010, highlighting the need for continual, careful monitoring of these data across the spectrum of HAI types. Infect Control Hosp Epidemiol 2016;1-14.