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Background. The incidence of skin and soft tissue infections (SSTIs) in the United States increased sharply after 2000 with the emergence of USA300 methicillin-resistant Staphylococcus aureus.We examined trends in SSTI incidence in 2006-2014 at the University of Chicago Medicine (UCM). Methods. Data were obtained for patient encounters at UCM with an International Classification of Diseases, Ninth Revisioncoded SSTI diagnosis between January 1, 2006 and March 31, 2014. Incidence density was calculated per 1000 encounters by quarter and year. Encounters were stratified by inpatient, outpatient clinic and emergency department (ED) encounters and by age group, gender, and race. Poisson regression was used to assess change over time. Results. In 2006-2014, data were collected for 38 201 SSTI-associated encounters among 31 869 subjects. Among all patients treated at UCM, there was a decrease of 1% per year in the incidence of SSTIs during 2006-2013, with an overall decrease of 16%. There was a significant decrease in SSTI-related encounters among inpatients (rate ratio [RR] = 0.97; 95% confidence interval [CI], .96-.98), ED patients (RR = 0.98; 95% CI, .97-.98), adults (RR = 0.98; 95% CI, .97-.98), children (RR = 0.96; 95% CI, .95-.97), and African Americans (RR = 0.99; 95% CI, .98-.99). There was an annual seasonal trend, with the peak incidence occurring during the late summer. Conclusions. The incidence of SSTIs at UCM decreased in children and adults with seasonal variation, peaking during the summer months. This suggests a reversal of the massive increase in SSTI incidence in the United States after 2000. [ABSTRACT FROM AUTHOR]

In this longitudinal study, patients with a Staphylococcus aureus skin infection were more likely to suffer a recurrence if household fomites were contaminated with methicillin-resistant S. aureus. Interventions to prevent recurrence may be enhanced by decontamination of household fomites.Background. Many patients suffer from recurrent Staphylococcus aureus infections, but there are few data examining recurrence predictors.Methods. We followed adults and children after treatment for S. aureus skin infections and their household contacts in Los Angeles and Chicago. We surveyed subjects for S. aureus body colonization, household fomite contamination, and behavioral and clinical factors at baseline and 3 and 6 months later. Using repeated measures modeling, we examined host, pathogen, behavioral, and clinical factors associated with recurrence.Results. Among 330 index subjects, 182 (55%) were infected with an isolate of the USA300 methicillin-resistant S. aureus (MRSA) genetic background. Recurrences occurred in 39% by month 3 and 51% by month 6. Among 588 household contacts, 10% reported a skin infection by month 3 and 13% by month 6. Among index subjects, recurrence was associated with (P < .05) Los Angeles site, diabetes, recent hospitalization, recent skin infection, recent cephalexin use, and household S. aureus or MRSA fomite contamination; recurrence was inversely associated with recent contact sports participation. In the multivariate model, independent predictors of recurrence in index patients were recent hospitalization, household MRSA fomite contamination, and lack of recent contact sports participation. Among household contacts, independent predictors of subsequent skin infection were Chicago site, antibiotic use in the prior year, and skin infection in the prior 3 months.Conclusions. In our longitudinal study, patients with a S. aureus skin infection were more likely to suffer a recurrence if household fomites were MRSA contaminated. Interventions to prevent recurrence may be enhanced by decontamination of household fomites. [ABSTRACT FROM PUBLISHER]

Background Staphylococcus aureus is a human pathogen responsible for substantial morbidity and mortality through its ability to cause a number of human infections including bacteremia, pneumonia and soft tissue infections. Of great concern is the emergence and dissemination of methicillin-resistant Staphylococcus aureus strains (MRSA) that are resistant to nearly all ß-lactams. The emergence of the USA300 MRSA genetic background among community associated S. aureus infections (CA-MRSA) in the USA was followed by the disappearance of USA400 CA-MRSA isolates. Results To gain a greater understanding of the potential fitness advantages and virulence capacity of S. aureus USA300 clones, we performed whole genome sequencing of 15 USA300 and 4 USA400 clinical isolates. A comparison of representative genomes of the USA300 and USA400 pulsotypes indicates a number of differences in mobile genome elements. We examined the in vitro gene expression profiles by microarray hybridization and the in vivo transcriptomes during lung infection in mice of a USA300 and a USA400 MRSA strain by performing complete genome qRT-PCR analysis. The unique presence and increased expression of 6 exotoxins in USA300 (12- to 600-fold) compared to USA400 may contribute to the increased virulence of USA300 clones. Importantly, we also observed the up-regulation of prophage genes in USA300 (compared with USA400) during mouse lung infection (including genes encoded by both prophages FSa2usa and FSa3usa), suggesting that these prophages may play an important role in vivo by contributing to the elevated virulence characteristic of the USA300 clone. Conclusions We observed differences in the genetic content of USA300 and USA400 strains, as well as significant differences of in vitro and in vivo gene expression of mobile elements in a lung pneumonia model. This is the first study to document the global transcription differences between USA300 and USA400 strains during both in vitro and in vivo growth. [ABSTRACT FROM AUTHOR]

Examining 4171 bacteremia episodes in 2008–2011, community-onset methicillin-resistant Staphylococcus aureus (MRSA) rates differed dramatically at 5 US academic medical centers. USA300 accounted for 52% of genotyped MRSA isolates, varying by center from 35% to 80%.Background. The incidence of community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) bacteremia rose from the late 1990s through the 2000s. However, hospital-onset (HO) MRSA rates have recently declined in the United States and Europe.Methods. Data were abstracted from infection prevention databases between 1 January 2008 and 31 December 2011 at 5 US academic medical centers to determine the number of single-patient blood cultures positive for MRSA and methicillin-susceptible S. aureus (MSSA) per calendar year, stratified into CO and HO infections.Results. Across the 5 centers, 4171 episodes of bacteremia were identified. Center A (Los Angeles, California) experienced a significant decline in CO-MRSA bacteremia rates (from a peak in 2009 of 0.42 to 0.18 per 1000 patient-days in 2011 [P = .005]), whereas CO-MSSA rates remained stable. Centers B (San Francisco, California), D (Chicago, Illinois), and E (Raleigh-Durham, North Carolina) experienced a stable incidence of CO-MRSA and CO-MSSA bacteremia. In contrast, at center C (New York, New York), the incidence of CO-MRSA increased >3-fold (from 0.11 to 0.34 cases per 1000 patient-days [P < .001]). At most of the sites, HO-MRSA decreased and HO-MSSA rates were stable. USA300 accounted for 52% (104/202) of genotyped MRSA isolates overall, but this varied by center, ranging from 35% to 80%.Conclusions. CO-MRSA rates and the contribution of USA300 MRSA varied dramatically across diverse geographical areas in the United States. Enhanced infection control efforts are unlikely to account for such variation in CO infection rates. Bioecological and clinical explanations for geographical differences in CO-MRSA bacteremia rates merit further study. [ABSTRACT FROM AUTHOR]

Background Methicillin-resistant Staphylococcus aureus (MRSA) has been a deadly pathogen in healthcare settings since the 1960s, but MRSA epidemiology changed since 1990 with new genetically distinct strain types circulating among previously healthy people outside healthcare settings. Community-associated (CA) MRSA strains primarily cause skin and soft tissue infections, but may also cause life-threatening invasive infections. First seen in Australia and the U.S., it is a growing problem around the world. The U.S. has had the most widespread CA-MRSA epidemic, with strain type USA300 causing the great majority of infections. Individuals with either asymptomatic colonization or infection may transmit CAMRSA to others, largely by skin-to-skin contact. Control measures have focused on hospital transmission. Limited public health education has focused on care for skin infections. Methods We developed a fine-grained agent-based model for Chicago to identify where to target interventions to reduce CA-MRSA transmission. An agent-based model allows us to represent heterogeneity in population behavior, locations and contact patterns that are highly relevant for CA-MRSA transmission and control. Drawing on nationally representative survey data, the model represents variation in sociodemographics, locations, behaviors, and physical contact patterns. Transmission probabilities are based on a comprehensive literature review. Results Over multiple 10-year runs with one-hour ticks, our model generates temporal and geographic trends in CA-MRSA incidence similar to Chicago from 2001 to 2010. On average, a majority of transmission events occurred in households, and colonized rather than infected agents were the source of the great majority (over 95%) of transmission events. The key findings are that infected people are not the primary source of spread. Rather, the far greater number of colonized individuals must be targeted to reduce transmission. Conclusions Our findings suggest that current paradigms in MRSA control in the United States cannot be very effective in reducing the incidence of CA-MRSA infections. Furthermore, the control measures that have focused on hospitals are unlikely to have much population-wide impact on CA-MRSA rates. New strategies need to be developed, as the incidence of CA-MRSA is likely to continue to grow around the world. [ABSTRACT FROM AUTHOR]

Among 350 households of patients with Staphylococcus aureus skin infections, extra-nasal S. aureus colonization was common. USA300 MRSA appeared more transmissible among household members than other S. aureus strain types. Multiple S. aureus genetic backgrounds were present in many households.Background. The USA300 methicillin resistant Staphylococcus aureus (MRSA) genetic background has rapidly emerged as the predominant cause of community-associated S. aureus infections in the U.S. However, epidemiologic characteristics of S. aureus household transmission are poorly understood.Methods. We performed a cross-sectional study of adults and children with S. aureus skin infections and their household contacts in Los Angeles and Chicago. Subjects were surveyed for S. aureus colonization of the nares, oropharynx, and inguinal region and risk factors for S. aureus disease. All isolates underwent genetic typing.Results. We enrolled 1162 persons (350 index patients and 812 household members). The most common infection isolate characteristic was ST8/SCCmec IV, PVL+ MRSA (USA300) (53%). S. aureus colonized 40% (137/350) of index patients and 50% (405/812) of household contacts. A nares-only survey would have missed 48% of S. aureus and 51% of MRSA colonized persons. Sixty-five percent of households had >1 S. aureus genetic background identified and 26% of MRSA isolates in household contacts were discordant with the index patients' infecting MRSA strain type. Factors independently associated (P < .05) with the index strain type colonizing household contacts were recent skin infection, recent cephalexin use, and USA300 genetic background.Conclusions. In our study population, USA300 MRSA appeared more transmissible among household members compared with other S. aureus genetic backgrounds. Strain distribution was complex; >1 S. aureus genetic background was present in many households. S. aureus decolonization strategies may need to address extra-nasal colonization and the consequences of eradicating S. aureus genetic backgrounds infrequently associated with infection. [ABSTRACT FROM AUTHOR]

CA-MRSA infection, driven by the emergence of the USA300 genetic background, has become epidemic in the United States. USA300 isolates are hypervirulent, compared with other CA- and HA-MRSA strains, in experimental models of necrotizing pneumonia and skin infection. Interestingly, USA300 isolates also have increased expression of core genomic global regulatory and virulence factor genes, including agr and saeRS. To test the hypothesis that agr and saeRS promote the observed hypervirulent phenotype of USA300, isogenic deletion mutants of each were constructed in USA300. The effects of gene deletion on expression and protein abundance of selected downstream virulence genes were assessed by semiquantitative real-time reverse-transcriptase PCR (qRT-PCR) and western blot, respectively. The effects of gene deletion were also assessed in mouse models of necrotizing pneumonia and skin infection. Deletion of saeRS, and, to a lesser extent, agr, resulted in attenuated expression of the genes encoding a-hemolysin (hla) and the Panton-Valentine leukocidin (lukSFPV). Despite the differences in hla transcription, the toxin was undetectable in culture supernatants of either of the deletion mutants. Deletion of agr, but not saeRS, markedly increased the expression of the gene encoding protein A (spa), which correlated with increased protein abundance. Each deletion mutant demonstrated significant attenuation of virulence, compared with wild-type USA300, in mouse models of necrotizing pneumonia and skin infection. We conclude that agr and saeRS each independently contribute to the remarkable virulence of USA300, likely by means of their effects on expression of secreted toxins. [ABSTRACT FROM AUTHOR]

USA300 is the dominant strain responsible for community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) infections in most of the United States. We examined isolates from outbreaks of MRSA skin infections in rural southwestern Alaska in 1996 and 2000 (retrospective collection) and from the hospital serving this region in 2004-2006 (prospective collection). Among 36 retrospective collection isolates, 92% carried Panton-Valentine leukocidin (PVL) genes; all carried staphylococcal chromosomal cassette mec (SCCmec) type IV. None belonged to clonal complex (CC) 8, the CC associated with USA300; 57% were sequence type (ST) 1, and 26% were ST30; 61% were clindamycin resistant. In the prospective collection, 42 isolates were PVL+ and carried SCCmec type IV; 83.3% were ST1, 9.5% were ST30, and 7.1% were ST8. Among 120 prospective isolates, 57.5% were clindamycin resistant. CA-MRSA epidemiology in southwestern Alaska differs from that in the lower 48 states; ST8 strains were rarely identified and clindamycin resistance was common. [ABSTRACT FROM AUTHOR]

Background. A community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection has been defined as an MRSA infection in a patient who lacks specific risk factors for healthcare exposure. We sought to determine whether the absence or presence of these risk factors still predicts the phenotypic or genotypic characteristics of MRSA strains. Methods. All clinical MRSA isolates were prospectively collected at the University of Chicago Hospitals from July 2004 through June 2005. Patients were interviewed and/or their medical records were reviewed. Isolates underwent genotyping and susceptibility testing. Data on patients and isolates were stratified in accordance with 8 frequently cited criteria for the identification of CA-MRSA and compared for concordance. Results. Among 616 unique patients from whom MRSA isolates were recovered, 404 (65.6%) had risk factors for healthcare exposure. Of the 404 isolates recovered from these patients, 166 (41.1%) were clindamycin susceptible, 190 (47.0%) carried staphylococcal cassette chromosome mec (SCCmec) type IV, 145 (35.9%) carried the Panton- Valentine leukocidin genes (PVL+), and 162 (40.1%) were identified as sequence type (ST) 8 by multilocus sequence typing (MLST), all of which are characteristics commonly attributed to CA-MRSA strains. Conclusions. Association with the healthcare environment now has little predictive value for distinguishing patients with infection due to multidrug resistant MRSA isolates from those infected by CA-MRSA isolates, that is, isolates that are clindamycin-susceptible, PVL+, ST8, and/or contain SCCmec type IV. Defining CA-MRSA by the absence of risk factors for healthcare exposure greatly underestimates the burden of epidemic CA-MRSA disease. [ABSTRACT FROM AUTHOR]

This article presents the case of a 37-year-old man who presented for localized swelling and tenderness of his left leg below the knee. He suspected a spider bite. Examination revealed an area of erythema with a fluctuant area in the middle. His pulse rate was 115 and his blood pressure was 116/78 mm Hg. The clinical problem is discussed with a focus on soft-tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Necrotic skin lesions are a common presentation of staph infection and are often incorrectly attributed to bites by brown recluse spiders or insect bites. Therapy options are presented from topical applications to surgery.

We noted a marked increase in healthcare-associated (HA) methicillin-resistant Staphylococcus aureus (MRSA) infections caused by isolates phenotypically consistent with community-associated (CA)-MRSA strains. To study this trend, we retrospectively examined all HA-MRSA isolates from patients in our institution during 1999-2004. An isolate was considered an SCCmecIV phenotype if it had antimicrobial drug susceptibilities consistent with typical CA-MRSA isolates. Our phenotypic definition was validated in a limited subset of isolates by SCCmec genotype, pulsed-field gel electrophoresis, and multilocus sequence typing. Among 352 patients with HA-MRSA isolates, SCCmecIV phenotype increased from 17% in 1999 to 56% in 2003 (p < 0.0001). Antimicrobial drug-susceptibility phenotype and genotype were consistent in 21 (91%) of 23 isolates. In a multivariate model, the SCCmec type IV phenotype was independently associated with wound culture source, later year of collection, and MRSA isolated earlier during hospitalization. In conclusion, MRSA isolates phenotypically similar to CA strains have become the predominant isolates associated with HA-MRSA in our hospital. [ABSTRACT FROM AUTHOR]

We performed a prospective study of all inpatient and outpatient methicillin-resistant Staphylococcus aureus (MRSA) isolates identified at the University of Chicago Hospitals from November 2003 through November 2004. Differences in resistance to non-beta-lactam antimicrobial drugs were determined after stratification of the 578 MRSA isolates into 4 groups by patient age (pediatric vs. adult) and onset location (community vs. hospital). Non-beta-lactam resistance was significantly greater among the 288 adult than the 177 pediatric community-associated isolates for erythromycin (93.2 vs. 87.0%, p = 0.03), clindamycin (51.8 vs. 7.3%, p<0.001), ciprofloxacin (62.1 vs. 10.7%, p<0.001), gentamicin (11.1 vs. 1.1%, p<0.001), and tetracycline (19.9 vs. 6.4%, p<0.001). In contrast, hospital-associated MRSA isolates from children and adults had similar rates of non-beta-lactam antimicrobial drug resistance. In our region, clindamycin is an appropriate empiric therapy of community-associated MRSA infection in children but should be used with caution in adults. [ABSTRACT FROM AUTHOR]

The authors discusses the developments in applying new technology towards the whole-genome sequencing and the acquisition of staphylococcus aureus in hospital's intensive care units (ICU) in the U.S. One of the author's highlights the use of a genetic trait with phenotype of resistance to ß-lactam antibiotics. The other author also points out the importance of spectrum in pathogenic strain types.

The author reports on the treatment of methicillin-resistant S. aureus (MRSA) infections. Reasons why the development of medications to treat MRSA have been slow are mentioned, such as the lack of microbial targets. Steps which have been taken by researchers in treating MRSA are discussed. According to the article, research is being done regarding the treatment of MRSA by inhibiting its creation of a virulence factor. Steps which need to be taken before MRSA can be treated in this manner are mentioned.

Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]