Necrotizing Fasciitis Caused by Community-Associated Methicillin-Resistant<i>Staphylococcus aureus</i>in Los Angeles

Miller, Loren G.; Perdreau-Remington, Françoise; Rieg, Günter; Mehdi, Sheherbano; Perlroth, Josh; Bayer, Arnold S.; Tang, Angela; Phung, Tieu O.; Spellberg, Brad

doi:10.1056/nejmoa042683

Cited by 967 publications

(649 citation statements)

References 56 publications

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“…Analysis of representative strains demonstrated that virulence was considerably increased in the lineage that comprises USA300 compared with the other CC8 MRSA lineages. This is consistent with the reported potential of USA300 to cause severe and widespread disease (37,38).…”

Section: Discussionsupporting

confidence: 92%

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

Diep

Villaruz

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

361

373

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Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged worldwide. The United States, in particular, is experiencing a serious epidemic of CA-MRSA that is almost entirely caused by an extraordinarily infectious strain named USA300. However, the molecular determinants underlying the pathogenic success of CA-MRSA are mostly unknown. To gain insight into the evolution of the exceptional potential of USA300 to cause disease, we compared the phylogeny and virulence of USA300 with that of closely related MRSA clones. We discovered that the sublineage from which USA300 evolved is characterized by a phenotype of high virulence that is clearly distinct from other MRSA strains. Namely, USA300 and its progenitor, USA500, had high virulence in animal infection models and the capacity to evade innate host defense mechanisms. Furthermore, our results indicate that increased virulence in the USA300/USA500 sublineage is attributable to differential expression of core genome-encoded virulence determinants, such as phenol-soluble modulins and ␣-toxin. Notably, the fact that the virulence phenotype of USA300 was already established in its progenitor indicates that acquisition of mobile genetic elements has played a limited role in the evolution of USA300 virulence and points to a possibly different role of those elements. Thus, our results highlight the importance of differential gene expression in the evolution of USA300 virulence. This finding calls for a profound revision of our notion about CA-MRSA pathogenesis at the molecular level and has important implications for design of therapeutics directed against CA-MRSA.

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Section: Discussionsupporting

confidence: 92%

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

Diep

Villaruz

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

361

373

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“…Type I ACME has been postulated to contribute to growth and survival of USA300 within the host, and promote colonization of the human skin [26]. ACME is integrated downstream of type IV SCCmec (Figure 2), utilizing the same cassette chromosome recombinases A and B (ccrAB) contained with SCCmec for mobilization and transfer [15][16][17][18][19][20][21][22][23][24]34]. Type I ACME is a distinctive genetic feature of the USA300 pandemic clone [26,34,35], although ACME-like elements have been detected in sporadic MRSA [32][33][34].…”

Section: Unique Genomic Contentsmentioning

confidence: 99%

“…Not seen before the year 2000, USA300 is now pandemic in communities across 38 U.S. states, Canada, and 9 European countries [11]. The pandemic clone USA300 has been implicated in unusually severe human diseases, including endocarditis, pneumonia, sepsis, and necrotizing fasciitis [16,17,29]. Remarkably, the introduction of USA300 into a new geographic area has often been associated with the displacement of locally endemic CA-MRSA strains belonging to ST1, ST30, ST59 and ST80 clonal lineages [22,23,32,33].…”

Section: Community-associated Clones Of Mrsamentioning

confidence: 99%

The role of virulence determinants in community-associated MRSA pathogenesis

Diep

Otto

2008

Trends in Microbiology

287

279

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The recent emergence of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) marked a quantum step change in the biology and epidemiology of a major human pathogen. Various virulence determinants unique to CA-MRSA have been recently uncovered, shedding light on how these strains spread easily and sustainably among humans and frequently cause severe disease. The role of the Panton Valentine leukocidin (PVL) in CA-MRSA pathogenesis is a matter of much debate. While epidemiological data have suggested a role of PVL in the CA-MRSA disease process, recent data from relevant animal models suggest that PVL does not impact virulence of prevalent CA-MRSA strains. Identifying specialized pathogenic traits of CA-MRSA remains a challenge that will yield new diagnostic tools and therapeutic targets for drug and vaccine development.

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“…HA-MRSA strains, which have circulated in healthcare settings for decades, are associated with pneumonia, bacteraemia and other invasive infections in patients with co-morbid illnesses in healthcare facilities (Mulligan et al, 1993). While CA-MRSA usually causes skin and soft tissue infections in otherwise healthy individuals (Watkins et al, 2012), more severe, invasive diseases may occur and can include necrotizing pneumonia (CDC, 2007;Kwong et al, 2012), pyomyositis and necrotizing fasciitis (Miller et al, 2005;Pannaraj et al, 2006), sepsis (Fortunov et al, 2006), osteomyelitis (Bocchini et al, 2006) or septic arthritis (Arnold et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Natural and ion-exchanged illite clays reduce bacterial burden and inflammation in cutaneous meticillin-resistant Staphylococcus aureus infections in mice

Otto

Kilbourne

Haydel

2016

Journal of Medical Microbiology

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Discoveries associated with antibacterial activity of hydrated clays necessitate assessments of in vivo efficacy, practical use and safety. Surface properties of clays can lead to variations in the composition and abundance of bound compounds or ions, thus affecting antibacterial activity. Since exchangeable metal ions released from the clay surface are responsible for in vitro antibacterial activity, we evaluated the in vivo antibacterial efficacy of four natural clays (one illite clay, two montmorillonite clays and one kaolinite clay) and three ion-exchanged, antibacterial clays against superficial, cutaneous meticillin-resistant Staphylococcus aureus (MRSA) infections in mice. Superficial, cutaneous wounds on the back of SKH1-Elite mice were generated and subsequently infected with MRSA. Following twice daily applications of a hydrated clay poultice to infected wounds for 7 days, we observed significant differences in the in vivo antibacterial efficacy between different types of clays. The natural and ion-exchanged illite clays performed best, as measured by bacterial load, inflammatory response and gross wound morphology with significant decreases in bacterial viability and dermatitis. Topical application of kaolinite clay was the least effective, resulting in the lowest decrease in bacterial load and exhibiting severe dermatitis. These data suggest that specific types of clays may offer a complementary and integrative strategy for topically treating MRSA and other cutaneous infections. However, since natural clays exhibit in vitro antibacterial variability and vary vastly in surface chemistries, adsorptive/absorptive characteristics and structural composition, the properties and characteristics of illite clays could aid in the development of standardized and customized aluminosilicates for topical infections.

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Necrotizing Fasciitis Caused by Community-Associated Methicillin-ResistantStaphylococcus aureusin Los Angeles

Abstract: Necrotizing fasciitis caused by community-associated MRSA is an emerging clinical entity. In areas in which community-associated MRSA infection is endemic, empirical treatment of suspected necrotizing fasciitis should include antibiotics predictably active against this pathogen.

Cited by 967 publications

References 56 publications

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

The role of virulence determinants in community-associated MRSA pathogenesis

Natural and ion-exchanged illite clays reduce bacterial burden and inflammation in cutaneous meticillin-resistant Staphylococcus aureus infections in mice

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