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Background: Understanding the changing epidemiology of Staphylococcus aureus bacteremia, as well as the variables associated with poor outcomes, can yield insight into potential interventions., Methods: This study was a retrospective, observational cohort study of adult patients at an academic medical center in New York City who had S. aureus bloodstream infections between 1 January 2007 and 31 December 2015. Participants were divided into 3 periods: group 1 (2007-2009), group 2 (2010-2012), and group 3 (2013-2015) for trend analysis. All clinical strains were genotyped (spa.). The main outcome was 30-day all-cause mortality., Results: There were 1264 episodes of methicillin-susceptible S. aureus (MSSA) and 875 episodes of methicillin-resistant S. aureus (MRSA) bacteremia, with a rising proportion due to MSSA (55% group 1; 59% group 2; 63% group 3; P = .03.) There were no significant changes in average age, gender, Charlson score, and distribution of strain genotypes. Mortality in MRSA infection was unchanged (25% group 1; 25% group 2; 26% group 3), while mortality in MSSA infection significantly declined (18% group 1; 18% group 2; 13% group 3). The average time to antistaphylococcal therapy (AST) in MSSA infection declined during the study (3.7 days group 1; 3.5 group 2; 2.2 group 3). In multivariate analysis, AST within 7 days of initial positive MSSA culture was associated with survival., Conclusions: Mortality in MSSA bloodstream infection is declining, associated with a decrease in time to targeted therapy. These results emphasize the potential for rapid diagnostics and early optimization of treatment to impact outcomes in MSSA bacteremia., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

House mice ( Mus musculus ) thrive in large urban centers worldwide. Nonetheless, little is known about the role that they may play in contributing to environmental contamination with potentially pathogenic bacteria. Here, we describe the fecal microbiome of house mice with emphasis on detection of pathogenic bacteria and antimicrobial resistance genes by molecular methods. Four hundred sixteen mice were collected from predominantly residential buildings in seven sites across New York City over a period of 13 months. 16S rRNA sequencing identified Bacteroidetes as dominant and revealed high levels of Proteobacteria A targeted PCR screen of 11 bacteria, as indicated by 16S rRNA analyses, found that mice are carriers of several gastrointestinal disease-causing agents, including Shigella , Salmonella , Clostridium difficile , and diarrheagenic Escherichia coli Furthermore, genes mediating antimicrobial resistance to fluoroquinolones ( qnrB ) and β-lactam drugs ( bla SHV and bla ACT/MIR ) were widely distributed. Culture and molecular strain typing of C. difficile Mice are commensal pests often found in close proximity to humans, especially in urban centers. We surveyed mice from seven sites across New York City and found multiple pathogenic bacteria associated with febrile and gastrointestinal disease as well as an array of antimicrobial resistance genes.Leptospira species. In concert, these findings support the need for further research into the role of house mice as potential reservoirs for human pathogens and antimicrobial resistance in the built environment. IMPORTANCE Mice are commensal pests often found in close proximity to humans, especially in urban centers. We surveyed mice from seven sites across New York City and found multiple pathogenic bacteria associated with febrile and gastrointestinal disease as well as an array of antimicrobial resistance genes., (Copyright © 2018 Williams et al.)

During the last 2 decades, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have dramatically increased the global burden of S. aureus infections. The pandemic sequence type (ST)8/pulsed-field gel type USA300 is the dominant CA-MRSA clone in the United States, but its evolutionary history and basis for biological success are incompletely understood. Here, we use whole-genome sequencing of 387 ST8 isolates drawn from an epidemiological network of CA-MRSA infections and colonizations in northern Manhattan to explore short-term evolution and transmission patterns. Phylogenetic analysis predicted that USA300 diverged from a most common recent ancestor around 1993. We found evidence for multiple introductions of USA300 and reconstructed the phylogeographic spread of isolates across neighborhoods. Using pair-wise single-nucleotide polymorphism distances as a measure of genetic relatedness between isolates, we observed that most USA300 isolates had become endemic in households, indicating their critical role as reservoirs for transmission and diversification. Using the maximum single-nucleotide polymorphism variability of isolates from within households as a threshold, we identified several possible transmission networks beyond households. Our study also revealed the evolution of a fluoroquinolone-resistant subpopulation in the mid-1990s and its subsequent expansion at a time of high-frequency outpatient antibiotic use. This high-resolution phylogenetic analysis of ST8 has documented the genomic changes associated with USA300 evolution and how some of its recent evolution has been shaped by antibiotic use. By integrating whole-genome sequencing with detailed epidemiological analyses, our study provides an important framework for delineating the full diversity and spread of USA300 and other emerging pathogens in large urban community populations.

The methicillin-susceptible Staphylococcus aureus (MSSA) clone sequence type (ST) 398 has increasingly been identified as a pathogen in diverse geographic settings, yet its epidemiology remains incompletely understood. In this case-control study of MSSA infections, we identified ST398 MSSA as both a major community- and hospital-associated MSSA pathogen in the Dominican neighborhood of northern Manhattan.

Unlabelled: A methicillin-resistant Staphylococcus aureus (MRSA) clone known as ST398 has emerged as a major cause of acute infections in individuals who have close contact with livestock. More recently, the emergence of an animal-independent ST398 methicillin-sensitive S. aureus (MSSA) clone has been documented in several countries. However, the limited surveillance of MSSA has precluded an accurate assessment of the global spread of ST398 and its clinical relevance. Here we provide evidence that ST398 is a frequent source of MSSA infections in northern Manhattan and is readily transmitted between individuals in households. This contrasts with the limited transmissibility of livestock-associated ST398 (LA-ST398) MRSA strains between humans. Our whole-genome sequence analysis revealed that the chromosome of the human-associated ST398 MSSA clone is smaller than that of the LA-ST398 MRSA reference strain S0385, due mainly to fewer mobile genetic elements (MGEs). In contrast, human ST398 MSSA isolates harbored the prophage ϕ3 and the human-specific immune evasion cluster (IEC) genes chp and scn. While most of the core genome was conserved between the human ST398 MSSA clone and S0385, these strains differed substantially in their repertoire and composition of intact adhesion genes. These genetic changes were associated with significantly enhanced adhesion of human ST398 MSSA isolates to human skin keratinocytes and keratin. We propose that the human ST398 MSSA clone can spread independent of animal contact using an optimized repertoire of MGEs and adhesion molecules adapted to transmission among humans., Importance: Staphylococcus aureus strains have generally been considered to be species specific. However, cross-species transfers of S. aureus clones, such as ST398 methicillin-resistant S. aureus (MRSA), from swine to humans have been reported. Recently, we observed the emergence of ST398 methicillin-susceptible S. aureus (MSSA) as a colonizing strain of humans in northern Manhattan. Here we report that ST398 is a frequent cause of MSSA infections in this urban setting. The ST398 MSSA clone was readily transmitted within households, independent of animal contact. We discovered that human ST398 MSSA genomes were smaller than that of the LA-ST398 strain S0385 due to fewer mobile genetic elements. Human and LA-ST398 strains also differed in their composition of adhesion genes and their ability to bind to human skin keratinocytes, providing a potential mechanism of S. aureus host adaptation. Our findings illustrate the importance of implementing molecular surveillance of MSSA given the evidence for the rapid and clinically undetected spread of ST398 MSSA.

Objectives: We combined social-network analysis and molecular epidemiology to investigate Staphylococcus aureus among drug users., Methods: From 2003 through 2005, we recruited adult drug users in Brooklyn, New York. Of 501 individuals recruited, 485 participated. Participants were screened for HIV infection and S. aureus carriage, and they answered a questionnaire assessing risk factors for S. aureus. Participants were asked to nominate up to 10 members of their social networks, and they were invited to recruit nominees to participate., Results: We identified 89 sociocentric risk networks, 1 of which contained 327 (67%) members. One third of participants were either colonized (20%) or infected (19%) with S. aureus. Overall strain similarity was unusually high, suggesting spread within and across networks. In multivariate analysis, 7 health-related and drug-use variables remained independently associated with infection. Moreover, 27% of nominees were not drug users., Conclusions: We found a large, linked, hidden network among participants, with no discernible clustering of closely related strains. Our results suggest that once a pathogen is introduced into a sociocentric network of active drug users, an identifiable community S. aureus reservoir is likely created, with significant linkages to the general population.

Background: Antibiotic-resistant Staphylococcus aureus infections have increased dramatically in the community, yet S. aureus nasal colonization has remained stable. The objectives of this study were to determine if S. aureus colonization is a useful proxy measure to study disease transmission and infection in community settings, and to identify potential community reservoirs., Methodology/principal Findings: Randomly selected households in Northern Manhattan, completed a structured social network questionnaire and provided nasal swabs that were typed by pulsed field gel electrophoresis to identify S. aureus colonizing strains. The main outcome measures were: 1) colonization with S. aureus; and 2) recent serious skin infection. Risk factor analyses were conducted at both the individual and the household levels; logistic regression models identified independent risks for household colonization and infection., Results: 321 surveyed households contained 914 members. The S. aureus prevalence was 25% and MRSA was 0.4%. More than 40% of households were colonized. Recent antibiotic use was the only significant correlate for household colonization (p = .002). Seventy-eight (24%) households reported serious skin infection. In contrast with colonization, five of the six risk factors that increased the risk of skin infection in the household at the univariate level remained independently significant in multivariable analysis: international travel, sports participation, surgery, antibiotic use and towel sharing. S. aureus colonization was not significantly associated with serious skin infection in any analysis. Among multiperson households with more than one person colonized, 50% carried the same strain., Conclusions/significance: The lack of association between S. aureus nasal colonization and serious skin infection underscores the need to explore alternative venues or body sites that may be crucial to transmission. Moreover, the magnitude of colonization and infection within the household suggests that households are an underappreciated and substantial community reservoir.

Closely related Staphylococcus aureus strains of ST398, an animal-associated strain, were identified in samples collected from humans in northern Manhattan, New York, NY, USA, and in the Dominican Republic. A large population in northern Manhattan has close ties to the Dominican Republic, suggesting international transmission.

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are becoming increasingly prevalent. There is geographic variation in their reported prevalence across the United States; however, studies reporting on CA-MRSA prevalence also demonstrate great variability in their case-finding methodology. We conducted a study to see how three different methods to ascertain CA-MRSA prevalence would lead to different estimates., Methods: Different methods were used to identify cases of CA-MRSA colonization and/or infection in New York City. Method 1: retrospective review of clinical and surveillance cultures identified through a hospital computer database. Method 2: prospective collection of surveillance cultures in the same hospital's emergency department. Method 3: prospective collection of surveillance cultures in a community setting., Results: Differing values for CA-MRSA prevalence resulted depending on the method and denominator used. All nares cultures as the denominator led to prevalence estimates of 0.3%-0.6%; all S. aureus as the denominator led to rates of 1.2%-5%; all MRSA as the denominator led to estimates of 5.5%-50%., Conclusions: A comparison of three methods revealed that variability in case-finding methodologies can lead to different prevalence estimates. Key factors to consider when comparing CA-MRSA rates include the definition of CA-MRSA, choice of denominator, and method and setting of sample collection.

Objective: To evaluate the relationship between Staphylococcus aureus nasal and tracheal colonization and infection in medical intensive care unit (MICU) patients. The primary outcome was the incidence of S. aureus infection in colonized versus non-colonized patients., Design: Prospective, observational cohort study. Patients admitted to the MICU during the study period were screened for S. aureus nasal and tracheal colonization by culture and a PCR assay twice weekly. Demographic, clinical, and microbiologic data were collected in the MICU and for 30 days after discharge. PFGE and antibiotic susceptibility testing were performed on all S. aureus nasal, tracheal, and clinical isolates., Results: Twenty-three percent of patients (47 of 208) were nasally colonized with S. aureus. Twenty-four percent of these patients developed S. aureus infections versus 2% of non-colonized patients (P < .01). Nine of 11 patients with both nasal colonization and infection were infected by their colonizing strain. Two of 47 nasally colonized patients developed an infection with a different strain of S. aureus. Fifty-three percent of intubated patients with nasal colonization (10 of 19) had tracheal colonization with S. aureus as opposed to 4.9% of intubated, non-colonized patients (3 of 61) (P < .01). Parenteral antibiotics were ineffective at clearing nasal colonization. PCR detected S. aureus colonization (nasal and tracheal) within 6.5 hours with a sensitivity of 83% and a specificity of 99%., Conclusions: The incidence of S. aureus infection was significantly elevated in nasally colonized MICU patients. Techniques to rapidly detect colonization in this population may make targeted topical prevention strategies feasible.

Forty-five cases of tuberculous meningitis at a large urban medical center were reviewed. Reasons for the continued incidence, prognostic factors, and current therapy of this life-threatening form of tuberculosis were examined. Thirty-nine of 45 patients were black, Hispanic, and/or 65 years of age or older (87%). Underlying conditions included alcohol abuse in 12, intravenous drug abuse in 7, recent steroid therapy in 4, head trauma in 4, recent pregnancy in 4, and the acquired immunodeficiency syndrome in 1. Thirty-four patients (76%) presented with altered mental status and/or focal neurologic findings. Significant mortality (31%) occurred despite the administration of antituberculous therapy to all but 1 patient. Six of 14 deaths (43%) occurred in the first week of hospitalization. One-third of survivors had neurologic sequelae at the time of follow-up. Neurologic deficits on admission, advanced age, and alcohol abuse were frequent among those who succumbed. Early recognition and treatment in hospital failed to improve outcome in advanced cases. From these findings we conclude that both aggressive treatment of primary tuberculous infections as well as prevention of secondary cases are necessary to effect any further reduction in the incidence, morbidity, and mortality of tuberculous meningitis.