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Widespread infections with community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) have occurred in the United States with the dissemination of the USA300 strain beginning in 2000. We examined 105 isolates obtained from children treated at the University of Chicago from 1994 to 1997 (75 methicillin-susceptible S. aureus [MSSA] and 30 MRSA isolates) in order to investigate for possible evidence of USA300 during this period. Infections were defined epidemiologically based on medical record review. The isolates underwent multilocus sequence typing (MLST), as well as assays for the Panton-Valentine leukocidin (PVL) genes, the protein A gene ( spa ), and arcA and opp3 , proxy markers for the arginine catabolic mobile element (ACME), characteristic of USA300 MRSA. MRSA isolates also underwent staphylococcal cassette chromosome mec (SCC mec ) typing and pulsed-field gel electrophoresis (PFGE) subtyping. MSSA isolates belonged to 17 sequence type (ST) groups. The 12 epidemiologically defined CA-MRSA infection isolates were either ST1 ( n = 4) or ST8 ( n = 8). They belonged to 3 different PFGE types: USA100 ( n = 1), USA400 ( n = 5), and USA500 ( n = 6). Among the CA-MRSA infection isolates, 8 (67%) were PVL + . None of the MRSA or MSSA isolates contained arcA or opp3 . Only one MRSA isolate was USA300 by PFGE. This was a health care-associated (HA) MRSA isolate, negative for PVL, that carried SCC mec type II. USA300 with its characteristic features was not identified in the collection from the years 1994 to 1997.

Objective.To understand the genotypic spectrum of environmental contamination ofStaphylococcus aureusin households and its persistenceDesign.Prospective longitudinal cohort investigation.Setting.Index participants identified at 2 academic medical centers.Participants.Adults and children withS. aureusskin infections and their household contacts in Los Angeles and Chicago.Methods.Household fomites were surveyed for contamination at baseline and 3 months. All isolates underwent genetic typing.Results.We enrolled 346 households, 88% of which completed the 3-month follow-up visit.S. aureusenvironmental contamination was 49% at baseline and 51% at 3 months. Among households with a USA300 methicillin-resistantS. aureus(MRSA) body infection isolate, environmental contamination with an indistinguishable MRSA strain was 58% at baseline and 63% at 3 months. Baseline factors associated with environmental contamination by the index subject’s infection isolate were body colonization by any household member with the index subject’s infection isolate at baseline (odds ratio [OR], 10.93 [95% confidence interval (CI), 5.75–20.79]), higher housing density (OR, 1.47 [95% CI, 1.10–1.96]), and more frequent household fomite cleaning (OR, 1.62 [95% CI, 1.16–2.27]). Household environmental contamination with the index subject’s infection strain at 3 months was associated with USA300 MRSA and a synergistic interaction between baseline environmental contamination and body colonization by any household member with the index subject’s infection strain.Conclusions.We found that infectingS. aureusisolates frequently persisted environmentally in households 3 months after skin infection. Presence of pathogenicS. aureusstrain type in the environment in a household may represent a persistent reservoir that places household members at risk of future infection.Infect Control Hosp Epidemiol2014;35(11):1373–1382

The surface capsular polysaccharide (CP) is a virulence factor that has been used as an antigen in several successful vaccines against bacterial pathogens. A vaccine has not yet been licensed against Staphylococcus aureus, although two multicomponent vaccines that contain CP antigens are in clinical trials. In this study, we evaluated CP production in USA300 methicillin-resistant S. aureus (MRSA) isolates that have become the predominant community-associated MRSA clones in the United States. We found that all 167 USA300 MRSA and 50 USA300 methicillin-susceptible S. aureus (MSSA) isolates were CP negative (CP−). Moreover, all 16 USA500 isolates, which have been postulated to be the progenitor lineage of USA300, were also CP−. Whole-genome sequence analysis of 146 CP− USA300 MRSA isolates revealed they all carry a cap5 locus with 4 conserved mutations compared with strain Newman. Genetic complementation experiments revealed that three of these mutations (in the cap5 promoter, cap5D nucleotide 994, and cap5E nucleotide 223) ablated CP production in USA300 and that Cap5E75 Asp, located in the coenzyme-binding domain, is essential for capsule production. All but three USA300 MSSA isolates had the same four cap5 mutations found in USA300 MRSA isolates. Most isolates with a USA500 pulsotype carried three of these four USA300-specific mutations, suggesting the fourth mutation occurred in the USA300 lineage. Phylogenetic analysis of the cap loci of our USA300 isolates as well as publicly available genomes from 41 other sequence types revealed that the USA300-specific cap5 mutations arose sequentially in S. aureus in a common ancestor of USA300 and USA500 isolates., IMPORTANCE The USA300 MRSA clone emerged as a community-associated pathogen in the United States nearly 20 years ago. Since then, it has rapidly disseminated and now causes health care-associated infections. This study shows that the CP-negative (CP−) phenotype has persisted among USA300 isolates and is a universal and characteristic trait of this highly successful MRSA lineage. It is important to note that a vaccine consisting solely of CP antigens would not likely demonstrate high efficacy in the U.S. population, where about half of MRSA isolates comprise USA300. Moreover, conversion of a USA300 strain to a CP-positive (CP+) phenotype is unlikely in vivo or in vitro since it would require the reversion of 3 mutations. We have also established that USA300 MSSA isolates and USA500 isolates are CP− and provide new insight into the evolution of the USA300 and USA500 lineages.

Staphylococcus aureus is a commensal species that can also be a formidable pathogen. In the United States, an epidemic of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has been occurring for the last 15 years. In the context of a study in which we identified patients with skin and soft tissue infections (SSTIs) and randomized them to receive one of two antimicrobial treatment regimens, we assessed S. aureus colonization in the nares, throat, and perianal skin on the day of enrollment and 40 days after therapy. We compared the prevalence of colonization between the SSTI patients and an uninfected control population. A total of 144 subjects and 130 controls, predominantly African American, participated in this study, and 116 returned for a 40-day follow-up visit. Of the SSTI patients, 76% were colonized with S. aureus at enrollment, as were 65% of the controls. Patients were more likely than the controls to be colonized with USA300 MRSA (62/144 [43.1%] versus 11/130 [8.5%], respectively; P < 0.001). The nares were not the most common site of colonization. The colonization prevalence diminished somewhat after antibiotic treatment but remained high. The isolates that colonized the controls were more likely than those in the patients to be methicillin-susceptible S. aureus (MSSA) (74/84 [88.1%] versus 56/106 [52.8%], respectively; P < 0.001). In conclusion, the prevalence of S. aureus colonization among SSTI patients was high and often involved USA300 MRSA. The prevalence diminished somewhat with antimicrobial therapy but remained high at the 40-day follow-up visit. Control subjects were also colonized at a high prevalence but most often with a genetic background not associated with a clinical infection in this study. S. aureus is a commensal species and a pathogen. Plans for decolonization or eradication should take this distinction into account.

Objective.To understand the genotypic spectrum of environmental contamination ofStaphylococcus aureusin households and its persistenceDesign.Prospective longitudinal cohort investigation.Setting.Index participants identified at 2 academic medical centers.Participants.Adults and children withS. aureusskin infections and their household contacts in Los Angeles and Chicago.Methods.Household fomites were surveyed for contamination at baseline and 3 months. All isolates underwent genetic typing.Results.We enrolled 346 households, 88% of which completed the 3-month follow-up visit.S. aureusenvironmental contamination was 49% at baseline and 51% at 3 months. Among households with a USA300 methicillin-resistantS. aureus(MRSA) body infection isolate, environmental contamination with an indistinguishable MRSA strain was 58% at baseline and 63% at 3 months. Baseline factors associated with environmental contamination by the index subject’s infection isolate were body colonization by any household member with the index subject’s infection isolate at baseline (odds ratio [OR], 10.93 [95% confidence interval (CI), 5.75–20.79]), higher housing density (OR, 1.47 [95% CI, 1.10–1.96]), and more frequent household fomite cleaning (OR, 1.62 [95% CI, 1.16–2.27]). Household environmental contamination with the index subject’s infection strain at 3 months was associated with USA300 MRSA and a synergistic interaction between baseline environmental contamination and body colonization by any household member with the index subject’s infection strain.Conclusions.We found that infectingS. aureusisolates frequently persisted environmentally in households 3 months after skin infection. Presence of pathogenicS. aureusstrain type in the environment in a household may represent a persistent reservoir that places household members at risk of future infection.Infect Control Hosp Epidemiol2014;35(11):1373–1382

Methicillin-resistant Staphylococcus aureus (MRSA) first appeared clinically in the early 1960s [1]. MRSA isolates became endemic in most US hospitals by the late 1980s [2–4]. In the 1990s, a new wave of MRSA infections occurred in community settings [3–8]. In many centers, MRSA isolates predominate as a cause of S. aureus community-onset (CO) infections, including bacteremia [3–5, 9]. Rather than being “escaped” hospital-based MRSA clones, the community MRSA strains were derived from methicillin-susceptible S. aureus (MSSA) strains that acquired a novel resistance element, SCCmec type IV [2, 4, 10–12]. These strain types, especially the USA300 genetic background, were highly virulent, often susceptible to multiple non–β-lactam antibiotics, and carried signature toxin genes (most commonly Panton-Valentine leukocidin [PVL]) rarely found in the older, hospital-acquired strain types [13]. USA300 also had a constitutive upregulation of several key virulence genes [14]. Driven by emergence of USA300, the incidence of MRSA infections rose dramatically in the early 2000s. In 2000, the Centers for Disease Control and Prevention (CDC) estimated that there were >30 000 hospitalizations for MRSA bacteremia [15]; however, more recent published reports have described declines in invasive MRSA infection rates, particularly in healthcare settings [16–20]. In the United States and the United Kingdom, the decline in MRSA bacteremia rates appears to have preceded enhanced infection prevention efforts in hospitals [21]. In a study of US military personnel and their dependents, rates of MRSA bacteremia declined between 2008 and 2011 [22]. However, to date, few reports have documented the incidence of MSSA bacteremia in this time period, or assessed potential geographic variations in CO infection rates, as opposed to hospital-onset (HO) rates. The current study was conducted to define trends in the annual incidence of MRSA and MSSA bacteremia at 5 large, geographically dispersed US academic medical centers to assess the incidence of HO and CO MSSA and MRSA bacteremia during a 4-year period.