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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.)

Prisons/jails are thought to amplify the transmission of Staphylococcus aureus (SA) particularly methicillin-resistant SA infection and colonisation. Two independently pooled cross-sectional samples of detainees being admitted or discharged from two New York State maximum-security prisons were used to explore this concept. Private interviews of participants were conducted, during which the anterior nares and oropharynx were sampled and assessed for SA colonisation. Log-binomial regression and correspondence analysis (CA) were used to evaluate the prevalence of colonisation at entry as compared with discharge. Approximately 51% of admitted (N = 404) and 41% of discharged (N = 439) female detainees were colonised with SA. Among males, 59% of those admitted (N = 427) and 49% of those discharged (N = 393) were colonised. Females had a statistically significant higher prevalence (1·26: P = 0·003) whereas males showed no significant difference (1·06; P = 0·003) in SA prevalence between entry and discharge. CA demonstrated that some strains, such as spa types t571 and t002, might have an affinity for certain mucosal sites. Contrary to our hypothesis, the prison setting did not amplify SA transmission, and CA proved to be a useful tool in describing the population structure of strains according to time and/or mucosal site.

Background: Staphylococcus epidermidis, a major component of skin flora, is an opportunist, often causing prosthetic device infections. A family of structurally related proteins mediates staphylococcal attachment to host tissues, contributing to the success of S. epidermidis as a pathogen. We examined the ability of the surface protein SdrF to adhere to keratin, a major molecule expressed on the skin surface., Methods: A heterologous Lactococcus lactis expression system was used to express SdrF and its ligand-binding domains. Adherence to keratin types 1 and 10, human foreskin keratinocytes, and nasal epithelial cells was examined., Results: SdrF bound human keratins 1 and 10 and adhered to keratinocytes and epithelial cells. Binding involved both the A and B domains. Anti-SdrF antibodies reduced adherence of S. epidermidis to keratin and keratinocytes. RNA interference reduced keratin synthesis in keratinocytes and, as a result, SdrF adherence. Direct force measurements using atomic force microscopy showed that SdrF mediates bacterial adhesion to keratin 10 through strong and weak bonds involving the A and B regions; strong adhesion was primarily mediated by the A region., Conclusions: These studies demonstrate that SdrF mediates adherence to human keratin and suggest that SdrF may facilitate S. epidermidis colonization of the skin., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Methicillin-susceptible Staphylococcus aureus (MSSA) accounts for the majority of S. aureus infections globally, and yet surprisingly little is known about its clonal evolution. We applied comparative whole-genome sequencing (WGS) analyses to epidemiologically and geographically diverse ST398-MSSA, a pandemic lineage affecting both humans and livestock. Bayesian phylogenetic analysis predicted divergence of human-associated ST398-MSSA ~40 years ago. Isolates from Midwestern pigs and veterinarians differed substantially from those in New York City (NYC). Pig ST398 strains contained a large region of recombination representing imports from multiple sequence types (STs). Phylogeographic analyses supported the spread of ST398-MSSA along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. Applying pairwise single-nucleotide polymorphism (SNP) distances as a measure of genetic relatedness between isolates, we observed that ST398 not only clustered in households but also frequently extended across local social networks. Isolates collected from environmental surfaces reflected the full diversity of colonizing individuals, highlighting their potentially critical role as reservoirs for transmission and diversification. Strikingly, we observed high within-host SNP variability compared to our previous studies on the dominant methicillin-resistant Staphylococcus aureus (MRSA) clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300-MRSA and ST398-MSSA. Taken together, our study reveals local and international routes of transmission for a major MSSA clone, indicating key impacts of recombination and mutation on genetic diversification and highlighting important ecological differences from epidemic USA300. Our study demonstrates extensive local and international routes of transmission for a major MSSA clone despite the lack of substantial antibiotic resistance., Importance: Unlike methicillin-resistant Staphylococcus aureus (MRSA), surprisingly little is known about the clonal evolution of methicillin-susceptible S. aureus (MSSA), although these strains account for the majority of S. aureus infections. To better understand how MSSA spreads and becomes established in communities, we applied comparative bacterial whole-genome sequencing to pandemic ST398-MSSA, a clone of clinical importance affecting humans and livestock in different geographic regions. Phylogeographic analyses identified that ST398-MSSA spread along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. We observed high within-host SNP variability compared to our previous studies on the dominant MRSA clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300 MRSA and ST398 MSSA., (Copyright © 2017 Uhlemann et al.)

Objective: To evaluate the association between HIV and Staphylococcus aureus colonization after confounding by incarceration is removed., Method: A cross sectional stratified study of all HIV infected and a random sample of HIV-uninfected inmates from two maximum-security prisons in New York State. Structured interviews were conducted. Anterior nares and oropharyngeal samples were cultured and S. aureus isolates were characterized. Log-binomial regression was used to assess the association between HIV and S. aureus colonization of the anterior nares and/or oropharynx and exclusive oropharynx colonization. Differences in S. aureus strain diversity between HIV-infected and uninfected individuals were assessed using Simpson's Index of Diversity., Results: Among 117 HIV infected and 351 HIV uninfected individuals assessed, 47% were colonized with S. aureus and 6% were colonized with methicillin resistant S. aureus. The prevalence of S. aureus colonization did not differ by HIV status (PR = 0.99, 95% CI = 0.76-1.24). HIV infected inmates were less likely to be exclusively colonized in the oropharynx (PR = 0.55, 95% CI = 0.30-0.99). Spa types t571 and t064 were both more prevalent among HIV infected individuals, however, strain diversity was similar in HIV infected and uninfected inmates., Conclusions: HIV infection was not associated with S. aureus colonization in these maximum-security prison populations, but was associated with decreased likelihood of oropharyngeal colonization. Factors that influence colonization site require further evaluation., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Importance: The role of environmental contamination in recurrent Staphylococcus aureus infections within households and its potential effect on intervention strategies has been debated recently., Objective: To assess whether household environmental contamination increases the risk for recurrent infection among individuals with a community-associated methicillin-resistant S aureus (MRSA) infection., Design, Setting, and Participants: This cohort study was conducted from November 1, 2011, to June 30, 2014, in the Columbia University Medical Center catchment area. All patients within 72 hours of presentation with skin or soft-tissue infections and blood, urine, or sputum cultures positive for MRSA were identified. Two hundred sixty-two patients met study inclusion criteria; 83 of these (31.7%) agreed to participate (index patients) with 214 household members. Participants were followed up for 6 months, and 62 of the 83 households (74.7%) completed follow-up. Participants and researchers were blinded to exposure status throughout the study. Follow-up was completed on June 30, 2014, and data were assessed from July 1, 2014, to February 19, 2016., Exposure: Concordant environmental contamination, defined as having an isolate with the identical staphylococcal protein A and staphylococcal chromosomal cassette mec type or antibiogram type as the index patient's clinical isolate, present on 1 or more environmental surfaces at the time of a home visit to the index patient after infection., Main Outcomes and Measures: Index recurrent infection, defined as any self-reported infection among the index patients during follow-up., Results: One patient did not complete any follow-up. Of the remaining 82 index patients, 53 (64.6%) were female and 59 (72.0%) were Hispanic. The mean age was 30 (SD, 20; range, 1-79) years. Forty-nine of 61 MRSA infections where the clinical isolate could be obtained (80.3%) were due to the epidemic strain USA300. Among the 82 households in which a patient had an index MRSA infection, the clinical isolate was present in the environment in 20 (24.4%) and not found in 62 (75.6%). Thirty-five patients (42.7%) reported a recurrent infection during follow-up, of whom 15 (42.9%) required hospitalization. Thirteen recurrent infections were from the 20 households (65.0%) with and 22 were from the 62 households (35.5%) without environmental contamination (P = .04). Environmental contamination increased the rate of index recurrent infection (incident rate ratio, 2.05; 95% CI, 1.03-4.10; P = .04)., Conclusions and Relevance: Household environmental contamination was associated with an increased rate of recurrent infection. Environmental decontamination should be considered as a strategy to prevent future MRSA infections, particularly among households where an infection has occurred.

Obesity increases a person's susceptibility to a variety of infections, including Staphylococcus aureus infections, which is an important cause of morbidity in correctional settings. Using a cross-sectional design, we assessed the association between obesity and S. aureus colonization, a risk factor for subsequent infection, in New York State maximum-security prisons (2011-2013). Anterior nares and oropharyngeal cultures were collected. Structured interviews and medical records were used to collect demographic, behavioral, and medical data. Body mass index (BMI; weight (kg)/height (m(2))) was categorized as 18.5-24.9, 25-29.9, 30-34.9, or ≥35. The association between BMI and S. aureus colonization was assessed using log-binomial regression. Thirty-eight percent of 638 female inmates and 26% of 794 male inmates had a BMI of 30 or higher. More than 40% of inmates were colonized. Female inmates with a BMI of 25-29.9 (prevalence ratio (PR) = 1.37, 95% confidence interval (CI): 1.06, 1.76), 30-34.9 (PR = 1.52, 95% CI: 1.17, 1.98), or ≥35 (PR = 1.49, 95% CI: 1.13, 1.96) had a higher likelihood of colonization than did those with a BMI of 18.5-24.9 after we controlled for age, educational level, smoking status, diabetes status, and presence of human immunodeficiency virus. Colonization was higher among male inmates with a BMI of 30-34.9 (PR = 1.27, 95% CI: 1.01, 1.61). Our findings demonstrate an association between BMI and S. aureus colonization among female prisoners. Potential contributory biologic and behavioral factors should be explored., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bacterial virulence is a multifaceted trait where the interactions between pathogen and host factors affect the severity and outcome of the infection. Toxin secretion is central to the biology of many bacterial pathogens and is widely accepted as playing a crucial role in disease pathology. To understand the relationship between toxicity and bacterial virulence in greater depth, we studied two sequenced collections of the major human pathogen Staphylococcus aureus and found an unexpected inverse correlation between bacterial toxicity and disease severity. By applying a functional genomics approach, we identified several novel toxicity-affecting loci responsible for the wide range in toxic phenotypes observed within these collections. To understand the apparent higher propensity of low toxicity isolates to cause bacteraemia, we performed several functional assays, and our findings suggest that within-host fitness differences between high- and low-toxicity isolates in human serum is a contributing factor. As invasive infections, such as bacteraemia, limit the opportunities for onward transmission, highly toxic strains could gain an additional between-host fitness advantage, potentially contributing to the maintenance of toxicity at the population level. Our results clearly demonstrate how evolutionary trade-offs between toxicity, relative fitness, and transmissibility are critical for understanding the multifaceted nature of bacterial virulence.

Background: Large outbreaks of Staphylococcus aureus (SA) infections have occurred in correctional facilities across the country. We aimed to define the epidemiological and microbiological determinants of SA infection in prisons to facilitate development of prevention strategies for this underserved population., Methods: We conducted a case-control study of SA infection at 2 New York State maximum security prisons. SA-infected inmates were matched with 3 uninfected controls. Subjects had cultures taken from sites of infection and colonization (nose and throat) and were interviewed via structured questionnaire. SA isolates were characterized by spa typing. Bivariate and multivariable analyses were conducted using conditional logistic regression., Results: Between March 2011 and January 2013, 82 cases were enrolled and matched with 246 controls. On bivariate analysis, the use of oral and topical antibiotics over the preceding 6 months was strongly associated with clinical infection (OR, 2.52; P < .001 and 4.38, P < .001, respectively). Inmates with clinical infection had 3.16 times the odds of being diabetic compared with inmates who did not have clinical infection (P < .001). Concurrent nasal and/or oropharyngeal colonization was also associated with an increased odds of infection (OR, 1.46; P = .002). Among colonized inmates, cases were significantly more likely to carry the SA clone spa t008 (usually representing the epidemic strain USA300) compared to controls (OR, 2.52; P = .01)., Conclusions: Several inmate characteristics were strongly associated with SA infection in the prison setting. Although many of these factors were likely present prior to incarceration, they may help medical staff identify prisoners for targeted prevention strategies., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Staphylococcus aureus, both methicillin susceptible and resistant, are now major community-based pathogens worldwide. The basis for this is multifactorial and includes the emergence of epidemic clones with enhanced virulence, antibiotic resistance, colonization potential, or transmissibility. Household reservoirs of these unique strains are crucial to their success as community-based pathogens. Staphylococci become resident in households, either as colonizers or environmental contaminants, increasing the risk for recurrent infections. Interactions of household members with others in different households or at community sites, including schools and daycare facilities, have a critical role in the ability of these strains to become endemic. Colonization density at these sites appears to have an important role in facilitating transmission. The integration of research tools, including whole-genome sequencing (WGS), mathematical modeling, and social network analysis, has provided additional insight into the transmission dynamics of these strains. Thus far, interventions designed to reduce recurrent infections among household members have had limited success, likely due to the multiplicity of potential sources for recolonization. The development of better strategies to reduce the number of household-based infections will depend on greater insight into the different factors that contribute to the success of these uniquely successful epidemic clones of S. aureus., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Diverse strain types of methicillin-resistant Staphylococcus aureus (MRSA) cause infections in community settings worldwide. To examine heterogeneity of spread within households and to identify common risk factors for household transmission across settings, primary data from studies conducted in New York (USA), Breda (The Netherlands), and Melbourne (Australia) were pooled. Following MRSA infection of the index patient, household members completed questionnaires and provided nasal swabs. Swabs positive for S. aureus were genotyped by spa sequencing. Poisson regression with robust error variance was used to estimate prevalence odds ratios for transmission of the clinical isolate to non-index household members. Great diversity of strain types existed across studies. Despite differences between studies, the index patient being colonized with the clinical isolate at the home visit (P < 0·01) and the percent of household members aged <18 years (P < 0·01) were independently associated with transmission. Targeted decolonization strategies could be used across geographical settings to limit household MRSA transmission.

Inmates of Rikers Island jail potentially introduce Staphylococcus aureus into New York State prisons upon transfer. In this study, methicillin-resistant Staphylococcus aureus isolates (n = 452), collected from infected inmates (2009 to 2013), were characterized. spa type t008 was the predominant clone identified, accounting for 82.3% of the isolates, with no evidence of mupirocin or chlorhexidine resistance., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

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.

To assess the prevalence and risk factors for colonization with Staphylococcus aureus in inmates entering two maximum-security prisons in New York State, USA, inmates (N=830) were interviewed and anterior nares and oropharyngeal samples collected. Isolates were characterized using spa typing. Overall, 50·5% of women and 58·3% of men were colonized with S. aureus and 10·6% of women and 5·9% of men were colonized with MRSA at either or both body sites. Of MSSA isolates, the major subtypes were spa type 008 and 002. Overall, risk factors for S. aureus colonization varied by gender and were only found in women and included younger age, fair/poor self-reported general health, and longer length of prior incarceration. Prevalence of MRSA colonization was 8·2%, nearly 10 times greater than in the general population. Control of epidemic S. aureus in prisons should consider the constant introduction of strains by new inmates.

Staphylococcus aureus is a prominent cause of human infections globally. The high prevalence of infections is compounded by antibiotic resistance--a significant problem for treatment. Methicillin-resistant S. aureus (MRSA) is endemic in hospitals and healthcare facilities worldwide, and is an increasingly common cause of community-associated bacterial infections in industrialized countries. Although much focus is placed on the role of S. aureus as a human pathogen, it is in fact a human commensal organism that has had a relatively long coexistence with the human host. Many S. aureus infections can be explained by host susceptibility or other predisposing risk factors. On the other hand, the emergence/re-emergence of successful S. aureus clones (referred to as epidemic waves) suggests a rapid bacterial adaption and evolution, which includes the emergence of antibiotic resistance and increased virulence and/or transmissibility. It is within this context that we review our understanding of selected S. aureus epidemic waves, and highlight the use of genome sequencing as a means to better understand the evolution of each lineage., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

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.

Sequence type 398 (ST398) Staphylococcus aureus, frequently carried by livestock, has caused severe human infections and often carries transmissible antibiotic resistance genes. Among methicillin-susceptible S. aureus isolates colonizing Dallas County Jail detainees, 13.2% were ST398, spa type t571, and were genetically similar to human colonization isolates from New York, Chicago, and the Dominican Republic.

While much is known about the geographic distribution of different clonal types of methicillin-resistant Staphylococcus aureus (MRSA), few studies have assessed the molecular epidemiology of methicillin-susceptible S. aureus (MSSA), despite its continued clinical importance. In each U.S. Census region, reference laboratories collected successive MSSA isolates from patients with invasive or superficial staphylococcal infections for use in the Tigecycline Evaluation and Surveillance Trial. All isolates from the periods of 2004 to 2005 and 2009 to 2010 underwent antimicrobial susceptibility testing and characterization of their staphylococcal protein A (spa) type. Of the 708 isolates analyzed, 274 spa types were identified and divided into 15 genetic clusters. The most common clones were spa t002 (n = 63, 8.9%) and t008 (n = 56, 7.9%). While the distribution of the predominant spa types did not differ by U.S. Census region or time period, spa t008 was nearly twice as common in community skin and soft tissue infections than in nosocomial bloodstream infections (11.1% versus 5.6%, respectively; P = 0.008). Despite such differences, both community and nosocomial settings had diverse staphylococcal clonal types representing all major spa clusters. In contrast to those of MRSA, MSSA infectious isolates show wide genetic diversity without clear geographical or temporal clustering. Notably, the prevalent MSSA strains (spa t002 and spa t008) are analogous to the predominant MRSA clones, further demonstrating the importance of both lineages.

Background: Ventricular assist devices (VADs) improve survival and quality of life in patients with advanced heart failure, but their use is frequently complicated by infection. There are limited data on the microbiology and epidemiology of these infections., Methods and Results: One hundred fifty patients scheduled for VAD implantation were enrolled (2006-2008) at 11 US cardiac centers and followed prospectively until transplantation, explantation for recovery, death, or for 1 year. Eighty-six patients (57%) received HeartMate II devices. Data were collected on potential preoperative, intraoperative, and postoperative risk factors for infection. Clinical, laboratory, and microbiological data were collected for suspected infections and evaluated by an infectious diseases specialist. Thirty-three patients (22%) developed 34 VAD-related infections with an incidence rate of 0.10 per 100 person-days (95% confidence interval, 0.073-0.142). The median time to infection was 68 days. The driveline was the most commonly infected site (n=28); 18 (64%) were associated with invasive disease. Staphylococci were the most common pathogen (47%), but pseudomonas or other Gram-negative bacteria caused 32% of infections. A history of depression and elevated baseline serum creatinine were independent predictors of VAD infection (adjusted hazard ratio=2.8 [P=0.007] and 1.7 [P=0.023], respectively). The HeartMate II was not associated with a decreased risk of infection. VAD infection increased 1-year mortality (adjusted hazard ratio=5.6; P<0.0001)., Conclusions: This prospective, multicenter study demonstrates that infection frequently complicates VAD placement and is a continuing problem despite the use of newer, smaller devices. Depression and renal dysfunction may increase the risk of VAD infection. VAD infection is a serious consequence because it adversely affects patient survival., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471795.

Staphylococcus aureus clonal complex 398 (CC398) isolates colonize livestock and can spread to human contacts. Genetic analysis of isolates epidemiologically associated with human-to-human, but not livestock, transmission in multiple countries and continents identified a common clade that was negative for tet(M) and positive for bacteriophage 3. Another group of human-to-human-transmitted isolates belonged to the common livestock-associated clade but had acquired a unique 7 bacteriophage.

Infections with vancomycin-intermediate Staphylococcus aureus (VISA) have been associated with vancomycin treatment failures and poor clinical outcomes. Routine identification of clinical isolates with increased vancomycin MICs remains challenging, and no molecular marker exists to aid in diagnosis of VISA strains. We tested vancomycin susceptibilities by using microscan, Etest, and population analyses in a collection of putative VISA, methicillin-resistant S. aureus, and methicillin-sensitive S. aureus (VSSA) infectious isolates from community- or hospital-associated S. aureus infections (n = 77) and identified 22 VISA and 9 heterogeneous VISA (hVISA) isolates. Sequencing of VISA candidate loci vraS, vraR, yvqF, graR, graS, walR, walK, and rpoB revealed a high diversity of nonsynonymous single-nucleotide polymorphisms (SNPs). For vraS, vraR, yvqF, walK, and rpoB, SNPs were more frequently present in VISA and hVISA than in VSSA isolates, whereas mutations in graR, graS, and walR were exclusively detected in VISA isolates. For each of the individual loci, SNPs were only detected in about half of the VISA isolates. All but one VISA isolate had at least one SNP in any of the genes sequenced, and isolates with an MIC of 6 or 8 μg/ml harbored at least 2 SNPs. Overall, increasing vancomycin MICs were paralleled by a higher proportion of isolates with SNPs. Depending on the clonal background, SNPs appeared to preferentially accumulate in vraS and vraR for sequence type 8 (ST8) and in walK and walR for ST5 isolates. Taken together, by comparing VISA, hVISA, and VSSA controls, we observed preferential clustering of SNPs in VISA candidate genes, with an unexpectedly high diversity across these loci. Our results support a polygenetic etiology of VISA.

Extranasal colonization is increasingly recognized as an important reservoir for Staphylococcus aureus among high-risk populations. We conducted a cross-sectional study of multiple body site colonization among 173 randomly selected STD clinic patients in Baltimore, Maryland. Staphylococcal carriage at extranasal sites, including the oropharynx, groin, rectum, and genitals, was common among study subjects. The USA300 clone was particularly associated with multiple sites of colonization compared with non-USA300 strains (p = .01). Given their high burden of multi-site colonization and confluence of established staphylococcal risk factors, STD clinic patients may represent a community-based reservoir for S. aureus and be well suited for innovative infection control initiatives., (Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: Little is known about the clonality of Staphylococcus epidermidis in the United States, although it is the predominant pathogen in infections involving prosthetic materials, including ventricular assist devices (VADs)., Methods: Seventy-five VAD recipients at 4 geographically diverse US cardiac centers were prospectively followed up to 1 year of VAD support. The anterior nares, sternum, and (future) driveline exit site were cultured for S. epidermidis before VAD insertion and at 7 times after surgery. Infection isolates were also collected. Isolates were typed by pulsed-field gel electrophoresis. A subset underwent susceptibility testing and staphylococcal chromosomal cassette mec and multilocus sequence typing., Results: A total of 1559 cultures yielded 565 S. epidermidis isolates; 254 of 548 typed isolates (46%) belonged to 1 of 7 clonal types as defined by pulsed-field gel electrophoresis. These clones were identified in up to 27 people distributed across all 4 cardiac centers. They caused 3 of 6 VAD-related infections. Disseminated clones were more antibiotic resistant than were less prevalent isolates (eg, 79% vs 54% methicillin resistant; P = .0021)., Conclusions: This study revealed that healthcare-associated S. epidermidis infection is remarkably clonal. We describe S. epidermidis clones that are highly resistant to antibiotics distributed across US cardiac centers. These clones may have determinants that enhance transmissibility, persistence, or invasiveness. Clinical Trials Registration. NCT01471795.

Staphylococcus aureus infections continue to pose a global public health problem. Frequently, this epidemic is driven by the successful spread of single S. aureus clones within a geographic region, but international travel has been recognized as a potential risk factor for S. aureus infections. To study the molecular epidemiology of S. aureus infections in the Caribbean, a major international tourist destination, we collected methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates from community-onset infections in the Dominican Republic (n = 112) and Martinique (n = 143). Isolates were characterized by a combination of pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing (MLST) typing. In Martinique, MRSA infections (n = 56) were mainly caused by t304-ST8 strains (n = 44), whereas MSSA isolates were derived from genetically diverse backgrounds. Among MRSA strains (n = 22) from the Dominican Republic, ST5, ST30, and ST72 predominated, while ST30 t665-PVL+ (30/90) accounted for a substantial number of MSSA infections. Despite epidemiological differences in sample collections from both countries, a considerable number of MSSA infections (~10%) were caused by ST5 and ST398 isolates at each site. Further phylogenetic analysis suggests the presence of lineages shared by the two countries, followed by recent genetic diversification unique to each site. Our findings also imply the frequent import and exchange of international S. aureus strains in the Caribbean.

The rapid dissemination of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) since the early 2000s and the appearance of new successful lineages is a matter of concern. The burden of these infections varies widely between different groups of individuals and in different regions of the world. Estimating the total burden of disease is therefore problematic. Skin and soft-tissue infections, often in otherwise healthy young individuals, are the most common clinical manifestation of these infections. The antibiotic susceptibilities of these strains also vary, although they are often more susceptible to 'traditional' antibiotics than related hospital-acquired strains. Preventing the dissemination of these organisms throughout the general population requires a multifaceted approach, including screening and decolonisation, general hygiene and cleaning measures, antibiotic stewardship programmes and, in the future, vaccination. The current evidence on the prevention and control of CA-MRSA is appraised and summarised in this review., (Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

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.

Background: The household is a recognized community reservoir for Staphylococcus aureus. This study investigated potential risk factors for intra-household S. aureus transmission, including the contribution of environmental contamination., Methods: We investigated intra-household S. aureus transmission using a sample of multiple member households from a community-based case-control study examining risk factors for CA-MRSA infection conducted in Northern Manhattan. During a home visit, index subjects completed a questionnaire. All consenting household members were swabbed, as were standardized environmental household items. Swabs were cultured for S. aureus. Positive isolates underwent further molecular characterization. Intra-household transmission was defined as having identical strains among two or more household members. Multiple logistic regression was used to identify independent risk factors for transmission., Results: We enrolled 291 households: 146 index cases, 145 index controls and 687 of their household contacts. The majority of indexes were Hispanic (85%), low income (74%), and female (67%), with a mean age of 31 (range 1-79). The average size of case and control households was 4 people. S. aureus colonized individuals in 62% of households and contaminated the environment in 54% of households. USA300 was the predominant clinical infection, colonizing and environmental strain. Eighty-one households had evidence of intra-household transmission: 55 (38%) case and 26 (18%) control households (P<.01). Environmental contamination with a colonizing or clinical infection strain (aOR: 5.4 [2.9-10.3] P<.01) and the presence of a child under 5 (aOR: 2.3 [1.2-4.5] P = .02) were independently associated with transmission. In separate multivariable models, environmental contamination was associated with transmission among case (aOR 3.3, p<.01) and control households (aOR 27.2, p<.01)., Conclusions: Environmental contamination with a colonizing or clinical infection strain was significantly and independently associated with transmission in a large community-based sample. Environmental contamination should be considered when treating S. aureus infections, particularly among households with multiple infected members.

Staphylococcus aureus is a frequent cause of serious infections and also a human commensal. The emergence of community-associated methicillin-resistant S. aureus led to a dramatic increase in skin and soft tissue infections worldwide. This epidemic has been driven by a limited number of clones, such as USA300 in the United States. To better understand the extent of USA300 evolution and diversification within communities, we performed comparative whole-genome sequencing of three clinical and five colonizing USA300 isolates collected longitudinally from three unrelated households over a 15-month period. Phylogenetic analysis that incorporated additional geographically diverse USA300 isolates indicated that all but one likely arose from a common recent ancestor. Although limited genetic adaptation occurred over the study period, the greatest genetic heterogeneity occurred between isolates from different households and within one heavily colonized household. This diversity allowed for a more accurate tracking of interpersonal USA300 transmission. Sequencing of persisting USA300 isolates revealed mutations in genes involved in major aspects of S. aureus function: adhesion, cell wall biosynthesis, virulence, and carbohydrate metabolism. Genetic variations also included accumulation of multiple polymorphisms within select genes of two multigene operons, suggestive of small genome rearrangements rather than de novo single point mutations. Such rearrangements have been underappreciated in S. aureus and may represent novel means of strain variation. Subtle genetic changes may contribute to USA300 fitness and persistence. Elucidation of small genome rearrangements reveals a potentially new and intriguing mechanism of directed S. aureus genome diversification in environmental niches and during pathogen-host interactions.

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.

Objective: Infections, especially those involving drivelines, are among the most serious complications that follow ventricular assist device implantation. Staphylococci are the most common causes of these infections. Once driveline infections are established, they can remain localized or progress as an ascending infection to cause metastatic seeding of other tissue sites. Although elaboration of biofilm appears to be critical in prosthetic device infections, its role as a facilitator of staphylococcal infection and migration along the driveline and other prosthetic devices is unclear., Methods: A murine model of driveline infection was used to investigate staphylococcal migration along the driveline. A biofilm-producing strain of Staphylococcus epidermidis and a Staphylococcus aureus strain and its intercellular adhesion gene cluster (ica)-negative (biofilm-deficient) isogenic mutant were used in these studies. Bacterial density on the driveline and the underlying tissue was measured over time. Scanning electron microscopy was used to examine the morphology of S epidermidis biofilm formation as the infection progressed., Results: The biofilm-deficient S aureus mutant was less effective at infecting and migrating along the driveline than the wild-type strain over time. However, the ica mutation had no effect on the ability of the strain to infect underlying tissue. S aureus exhibited more rapid migration than S epidermidis. Scanning electron microscopy revealed the deposition of host matrix on the Dacron material after implantation. This was followed by elaboration of a bacterial biofilm that correlated with more rapid migration along the driveline., Conclusions: Biofilm formation is a critical virulence determinant that facilitates the progression of drivelines infections., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Throat carriage (42.7%) of Staphylococcus aureus exceeded nasal carriage (35.0%) in 2 New York prisons. Methicillin resistance, primarily due to USA300, was high at both sites; 25% of dually colonized inmates had different strains. Strategies to reduce S. aureus transmission will need to consider the high frequency of throat colonization.

Objective: To test whether a critical care consult team can be used to identify patients who have methicillin-resistant Staphylococcus aureus nasal colonization during a window period at which they are at highest risk for methicillin-resistant S. aureus infection and can most benefit from topical decolonization strategies., Design: Prospective cohort study., Setting: Two adult tertiary care hospitals., Patients: Patients with at least one risk factor for methicillin-resistant S. aureus nasal colonization who were seen by a critical care consult team for potential intensive care unit admission were enrolled., Interventions: Nasal cultures for methicillin-resistant S. aureus were performed on all subjects. All subjects were followed for the development of a methicillin-resistant S. aureus infection for 60 days or until hospital discharge. Demographic and outcome data were recorded on all subjects., Measurements and Main Results: Two hundred subjects were enrolled. Overall 29 of 200 (14.5%) were found to have methicillin-resistant S. aureus nasal colonization. Methicillin-resistant S. aureus infections occurred in seven of 29 (24.1%) subjects with methicillin-resistant S. aureus nasal colonization vs. one of 171 (0.6%) subjects without methicillin-resistant S. aureus nasal colonization (p < .001). Methicillin-resistant S. aureus clinical specimens were recovered in 15 of 29 (51.7%) subjects with methicillin-resistant S. aureus nasal colonization vs. two of 171 (1.2%) without methicillin-resistant S. aureus nasal colonization., Conclusions: A critical care consult team can be used to rapidly recognize patients with methicillin-resistant S. aureus nasal colonization who are at very elevated risk for methicillin-resistant S. aureus infection. The use of such a team to recognize patients who have greatest potential benefit from decolonization techniques might reduce the burden of severe methicillin-resistant S. aureus infections.

Background: Little is known about the prevalence of Staphylococcus aureus nasal colonization and the epidemiology of methicillin-susceptible and methicillin-resistant S. aureus (MRSA) among cystic fibrosis (CF) patients and their household members., Objectives: We sought to determine the epidemiology of S. aureus among children and adolescents with CF and their household members., Methods: Three CF centers enrolled case subjects with at least 1 MRSA-positive respiratory tract culture from 2001 to 2006 and control subjects with MRSA-negative cultures. S. aureus isolates from the anterior nares of CF subjects and their household members were assessed for staphylococcal chromosomal cassette (SCC) mec type. Strain similarity was determined by pulsed-field gel electrophoresis., Results: S. aureus nasal colonization occurred in 52.4% (22/42), 27.0% (17/63), and 25.0% (72/288) of case, control, and household participants, respectively. Case subjects and their contacts were more likely to harbor MRSA in their nares and be from a multipatient CF family. Of 31 MRSA strains, 10 (32.3%) were SCCmec type IVa, associated with community-acquisition. Overall, 27.6% of 98 households had > or =2 members colonized with closely related isolates. Household members were equally likely to be colonized with closely related strains of MRSA (20/31, 65%) versus MSSA (38/80, 48%)., Conclusions: This study demonstrated that household members of CF children harbor both MSSA and MRSA, including CA-MRSA, and that S. aureus is transmitted within CF households. Carriage of S. aureus by household members of CF children may have implications for infection control and treatment strategies. Future studies should monitor the distribution and virulence of SCCmecA types in patients with CF.

Staphylococcus epidermidis remains the predominant pathogen in prosthetic-device infections. Ventricular assist devices, a recently developed form of therapy for end-stage congestive heart failure, have had considerable success. However, infections, most often caused by Staphylococcus epidermidis, have limited their long-term use. The transcutaneous driveline entry site acts as a potential portal of entry for bacteria, allowing development of either localized or systemic infections. A novel in vitro binding assay using explanted drivelines obtained from patients undergoing transplantation and a heterologous lactococcal system of surface protein expression were used to identify S. epidermidis surface components involved in the pathogenesis of driveline infections. Of the four components tested, SdrF, SdrG, PIA, and GehD, SdrF was identified as the primary ligand. SdrF adherence was mediated via its B domain attaching to host collagen deposited on the surface of the driveline. Antibodies directed against SdrF reduced adherence of S. epidermidis to the drivelines. SdrF was also found to adhere with high affinity to Dacron, the hydrophobic polymeric outer surface of drivelines. Solid phase binding assays showed that SdrF was also able to adhere to other hydrophobic artificial materials such as polystyrene. A murine model of infection was developed and used to test the role of SdrF during in vivo driveline infection. SdrF alone was able to mediate bacterial adherence to implanted drivelines. Anti-SdrF antibodies reduced S. epidermidis colonization of implanted drivelines. SdrF appears to play a key role in the initiation of ventricular assist device driveline infections caused by S. epidermidis. This pluripotential adherence capacity provides a potential pathway to infection with SdrF-positive commensal staphylococci first adhering to the external Dacron-coated driveline at the transcutaneous entry site, then spreading along the collagen-coated internal portion of the driveline to establish a localized infection. This capacity may also have relevance for other prosthetic device-related infections.

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.

Staphylococcus aureus is a leading cause of ventricular assist device-related infections. This study evaluated the protective effect against S. aureus infection of active and passive immunization that targeted 3 proteins involved in bacterial attachment to a murine intra-aortic polyurethane patch. Active immunization of mice with a combination of the A domains of clumping factor A (ClfA), fibronectin-binding protein A (FnBPA) and fibronectin-binding protein B or passive immunization with monoclonal antibodies against ClfA and FnBPA resulted in a higher level of protection than that obtained by vaccination with either protein or antibody alone. The combination of antibodies or protein antigens appears to provide enhanced protection against prosthetic-device infection.

Staphylococcus aureus is a versatile pathogen capable of causing a wide range of human diseases. However, the role of different virulence factors in the development of staphylococcal infections remains incompletely understood. Some clonal types are well equipped to cause disease across the globe, whereas others are facile at causing disease among community members. In this review, general aspects of staphylococcal pathogenesis are addressed, with emphasis on methicillin-resistant strains. Although methicillin-resistant S. aureus (MRSA) strains are not necessarily more virulent than methicillin-sensitive S. aureus strains, some MRSA strains contain factors or genetic backgrounds that may enhance their virulence or may enable them to cause particular clinical syndromes. We examine these pathogenic factors.

Methicillin-resistant Staphylococcus aureus is increasingly responsible for staphylococcal outbreaks in prison. There is limited information on the source of the outbreak strains, risk factors for infection, and transmission of these strains within a prison. We conducted a survey to determine the prevalence of nasal colonization with S. aureus in 2 New York State prisons. S. aureus isolates from clinical cultures collected from all New York State prisons during a 6-month period were compared with the colonizing strains. Analyses were conducted to determine whether prison-level characteristics were associated with colonization or infection with S. aureus. The colonization rate was 25.5% (124/487); 10.5% of the isolates were methicillin resistant, all were staphylococcal chromosomal cassette (SCC)mec type IV, and 61.5% were Panton Valentine leukocidin (PVL) positive. Surprisingly, 21.6% of the methicillin-susceptible isolates were also PVL positive. Of the clinical isolates, 48.3% were methicillin resistant, with 93.1% of the latter being SCCmec type IV and 48.3% being PVL positive. The predominant clone was USA 300. Prison-level risk factors for infection included the proportion of inmates with drug offenses, the length of inmate stay, and the jail from which inmates originated. This study suggests that both new and long-term inmates act as sources of S. aureus strains, with the more virulent of the latter preferentially being selected as pathogens.

A longitudinal study of 282 community-based drug users was conducted from February 1999 through September 2000. Both the incidence (15.0 cases per 100 person-years at risk; 95% confidence interval, 10.2-20.7 cases per 100 person-years at risk) and persistence of Staphylococcus aureus carriage were increased among human immunodeficiency virus (HIV)-seropositive individuals.

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.

Heterosexual transmission of community-associated methicillin-resistant Staphylococcus aureus has not been documented. As part of a survey conducted in northern Manhattan, we encountered 3 households in which heterosexual transmission was responsible for new community-associated methicillin-resistant S. aureus infection. The vaginal and inguinal isolates obtained from the sexual partners were USA 300. This report documents an important and previously unrecognized means of community-associated methicillin-resistant S. aureus colonization and transmission for these potentially invasive strains.

We reviewed published work examining the prevalence and risk factors for meticillin-resistant Staphylococcus aureus (MRSA) infection in two high-risk groups: prisoners and military enlistees. Significant risk factors for infection included prison occupation, gender, comorbidities, prior skin infection, and previous antibiotic use. Although characteristics such as hygiene, physical contact, and crowding were postulated as risk factors for MRSA infection, there were few epidemiological studies supporting these factors. Most studies identified were retrospective in design and only one study used prospective surveillance for MRSA colonisation among all individuals residing within a single military setting. Our results suggest that there is a high incidence of MRSA infection among individuals in prisons and military settings, but surveys that quantify the prevalence of MRSA colonisation among individuals living within these specialised settings are needed. A thorough examination of MRSA acquisition and transmission patterns in prisons and military settings could help elucidate preventive strategies in other crowded and closed settings.

Ventricular assist devices (VADs) are an important form of therapy for end-stage congestive heart failure. However, infection of the VAD, which is often caused by Staphylococcus aureus, poses a major threat to survival. Using a novel in vitro binding assay with VAD membranes and a heterologous lactococcal system of expression, we identify 3 S. aureus proteins--clumping factor A (ClfA) and fibronectin binding proteins A and B (FnBPA and FnBPB) as the main factors involved in adherence to VAD polyurethane membranes. Adherence is greatly diminished by long implantation times, reflecting a change in topological features of the VAD membrane, and is primarily mediated by the FnBPA domains in the staphylococcal proteins. We also compare the adherence of S. aureus mutant strains and show that other staphylococcal components appear to be involved in adherence to VAD membranes. Finally, we demonstrate that ClfA, FnBPA, and FnBPB mediate bacterial infection of implanted murine intra-aortic polyurethane patches.