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Journal ArticleDOI

Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era

01 Sep 2009-Journal of Clinical Investigation (American Society for Clinical Investigation)-Vol. 119, Iss: 9, pp 2464-2474
TL;DR: Progress made toward understanding the success of community-associated MRSA as a human pathogen is focused on, with an emphasis on genome-wide approaches and virulence determinants.
Abstract: Staphylococcus aureus is the leading cause of bacterial infections in developed countries and produces a wide spectrum of diseases, ranging from minor skin infections to fatal necrotizing pneumonia. Although S. aureus infections were historically treatable with common antibiotics, emergence of drug-resistant organisms is now a major concern. Methicillin-resistant S. aureus (MRSA) was endemic in hospitals by the late 1960s, but it appeared rapidly and unexpectedly in communities in the 1990s and is now prevalent worldwide. This Review focuses on progress made toward understanding the success of community-associated MRSA as a human pathogen, with an emphasis on genome-wide approaches and virulence determinants.

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Citations
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Journal ArticleDOI
TL;DR: A review of antibiotic resistance development over the past half-century can be found in this article, with the oft-restated conclusion that it is time to act and to restore the therapeutic applications of antibiotics.
Abstract: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.

4,364 citations

Journal ArticleDOI
TL;DR: A review of the most up-to-date knowledge and a perspective for the future prophylaxis or new treatments for CA-MRSA infections is provided in this paper.

1,367 citations

Journal ArticleDOI
TL;DR: Progressive alternate approaches including probiotics, antibodies, and vaccines have shown promising results in trials that suggest the role of these alternatives as preventive or adjunct therapies in future.
Abstract: The advent of multidrug resistance among pathogenic bacteria is imperiling the worth of antibiotics, which have previously transformed medical sciences. The crisis of antimicrobial resistance has been ascribed to the misuse of these agents and due to unavailability of newer drugs attributable to exigent regulatory requirements and reduced financial inducements. Comprehensive efforts are needed to minimize the pace of resistance by studying emergent microorganisms, resistance mechanisms, and antimicrobial agents. Multidisciplinary approaches are required across health care settings as well as environment and agriculture sectors. Progressive alternate approaches including probiotics, antibodies, and vaccines have shown promising results in trials that suggest the role of these alternatives as preventive or adjunct therapies in future.

1,328 citations


Cites background from "Reemergence of antibiotic-resistant..."

  • ...Although most of the CA-MRSA properties are similar to MRSA, CA-MRSA has some additional characteristics as well such as different mec gene clusters and genes encoding the cytotoxic Panton–Valentine leukocidin.(48,49)...

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Journal ArticleDOI
TL;DR: Structural and functional analysis has identified four distinct classes of surface proteins, of which microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) are the largest class, and targeting them with vaccines could combat S. aureus infections.
Abstract: Staphylococcus aureus is an important opportunistic pathogen and persistently colonizes about 20% of the human population. Its surface is 'decorated' with proteins that are covalently anchored to the cell wall peptidoglycan. Structural and functional analysis has identified four distinct classes of surface proteins, of which microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) are the largest class. These surface proteins have numerous functions, including adhesion to and invasion of host cells and tissues, evasion of immune responses and biofilm formation. Thus, cell wall-anchored proteins are essential virulence factors for the survival of S. aureus in the commensal state and during invasive infections, and targeting them with vaccines could combat S. aureus infections.

1,116 citations

Journal ArticleDOI
TL;DR: The origin of MRSA is described, with emphasis on the diverse nature of staphylococcal cassette chromosome mec (SCCmec).
Abstract: SUMMARY Staphylococcus aureus, a major human pathogen, has a collection of virulence factors and the ability to acquire resistance to most antibiotics. This ability is further augmented by constant emergence of new clones, making S. aureus a “superbug.” Clinical use of methicillin has led to the appearance of methicillin-resistant S. aureus (MRSA). The past few decades have witnessed the existence of new MRSA clones. Unlike traditional MRSA residing in hospitals, the new clones can invade community settings and infect people without predisposing risk factors. This evolution continues with the buildup of the MRSA reservoir in companion and food animals. This review focuses on imparting a better understanding of MRSA evolution and its molecular characterization and epidemiology. We first describe the origin of MRSA, with emphasis on the diverse nature of staphylococcal cassette chromosome mec (SCCmec). mecA and its new homologues (mecB, mecC, and mecD), SCCmec types (13 SCCmec types have been discovered to date), and their classification criteria are discussed. The review then describes various typing methods applied to study the molecular epidemiology and evolutionary nature of MRSA. Starting with the historical methods and continuing to the advanced whole-genome approaches, typing of collections of MRSA has shed light on the origin, spread, and evolutionary pathways of MRSA clones.

776 citations


Cites background from "Reemergence of antibiotic-resistant..."

  • ...the mid-1990s, and LA-MRSA clones from the beginning of this century (15, 421, 422)....

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References
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Journal ArticleDOI
17 Oct 2007-JAMA
TL;DR: Invasive MRSA infection affects certain populations disproportionately and is a major public health problem primarily related to health care but no longer confined to intensive care units, acute care hospitals, or any health care institution.
Abstract: ContextAs the epidemiology of infections with methicillin-resistant Staphylococcus aureus (MRSA) changes, accurate information on the scope and magnitude of MRSA infections in the US population is needed.ObjectivesTo describe the incidence and distribution of invasive MRSA disease in 9 US communities and to estimate the burden of invasive MRSA infections in the United States in 2005.Design and SettingActive, population-based surveillance for invasive MRSA in 9 sites participating in the Active Bacterial Core surveillance (ABCs)/Emerging Infections Program Network from July 2004 through December 2005. Reports of MRSA were investigated and classified as either health care–associated (either hospital-onset or community-onset) or community-associated (patients without established health care risk factors for MRSA).Main Outcome MeasuresIncidence rates and estimated number of invasive MRSA infections and in-hospital deaths among patients with MRSA in the United States in 2005; interval estimates of incidence excluding 1 site that appeared to be an outlier with the highest incidence; molecular characterization of infecting strains.ResultsThere were 8987 observed cases of invasive MRSA reported during the surveillance period. Most MRSA infections were health care–associated: 5250 (58.4%) were community-onset infections, 2389 (26.6%) were hospital-onset infections; 1234 (13.7%) were community-associated infections, and 114 (1.3%) could not be classified. In 2005, the standardized incidence rate of invasive MRSA was 31.8 per 100 000 (interval estimate, 24.4-35.2). Incidence rates were highest among persons 65 years and older (127.7 per 100 000; interval estimate, 92.6-156.9), blacks (66.5 per 100 000; interval estimate, 43.5-63.1), and males (37.5 per 100 000; interval estimate, 26.8-39.5). There were 1598 in-hospital deaths among patients with MRSA infection during the surveillance period. In 2005, the standardized mortality rate was 6.3 per 100 000 (interval estimate, 3.3-7.5). Molecular testing identified strains historically associated with community-associated disease outbreaks recovered from cultures in both hospital-onset and community-onset health care–associated infections in all surveillance areas.ConclusionsInvasive MRSA infection affects certain populations disproportionately. It is a major public health problem primarily related to health care but no longer confined to intensive care units, acute care hospitals, or any health care institution.

3,803 citations

Journal ArticleDOI
TL;DR: A multilocus sequence typing (MLST) scheme has been developed for Staphylococcus aureus and provides an unambiguous method for assigning MRSA and MSSA isolates to known clones or assigning them as novel clones via the Internet.
Abstract: A multilocus sequence typing (MLST) scheme has been developed for Staphylococcus aureus. The sequences of internal fragments of seven housekeeping genes were obtained for 155 S. aureus isolates from patients with community-acquired and hospital-acquired invasive disease in the Oxford, United Kingdom, area. Fifty-three different allelic profiles were identified, and 17 of these were represented by at least two isolates. The MLST scheme was highly discriminatory and was validated by showing that pairs of isolates with the same allelic profile produced very similar SmaI restriction fragment patterns by pulsed-field gel electrophoresis. All 22 isolates with the most prevalent allelic profile were methicillin-resistant S. aureus (MRSA) isolates and had allelic profiles identical to that of a reference strain of the epidemic MRSA clone 16 (EMRSA-16). Four MRSA isolates that were identical in allelic profile to the other major epidemic MRSA clone prevalent in British hospitals (clone EMRSA-15) were also identified. The majority of isolates (81%) were methicillin-susceptible S. aureus (MSSA) isolates, and seven MSSA clones included five or more isolates. Three of the MSSA clones included at least five isolates from patients with community-acquired invasive disease and may represent virulent clones with an increased ability to cause disease in otherwise healthy individuals. The most prevalent MSSA clone (17 isolates) was very closely related to EMRSA-16, and the success of the latter clone at causing disease in hospitals may be due to its emergence from a virulent MSSA clone that was already a major cause of invasive disease in both the community and hospital settings. MLST provides an unambiguous method for assigning MRSA and MSSA isolates to known clones or assigning them as novel clones via the Internet.

2,809 citations

Journal ArticleDOI
TL;DR: Panton-Valentine leukocidin genes were detected in 93% of strains associated with furunculosis and in 85% of those associated with severe necrotic hemorrhagic pneumonia (all community-acquired), and it appears that PVL is mainly associated with nec rotic lesions involving the skin or mucosa.
Abstract: Panton-Valentine leukocidin (PVL) is a cytotoxin that causes leukocyte destruction and tissue necrosis. It is produced by fewer than 5% of Staphylococcus aureus strains. A collection of 172 S. aureus strains were screened for PVL genes by polymerase chain reaction amplification. PVL genes were detected in 93% of strains associated with furunculosis and in 85% of those associated with severe necrotic hemorrhagic pneumonia (all community-acquired). They were detected in 55% of cellulitis strains, 50% of cutaneous abscess strains, 23% of osteomyelitis strains, and 13% of finger-pulp-infection strains. PVL genes were not detected in strains responsible for other infections, such as infective endocarditis, mediastinitis, hospital-acquired pneumonia, urinary tract infection, and enterocolitis, or in those associated with toxic-shock syndrome. It thus appears that PVL is mainly associated with necrotic lesions involving the skin or mucosa.

2,463 citations

Journal ArticleDOI
TL;DR: MRSA is the most common identifiable cause of skin and soft-tissue infections among patients presenting to emergency departments in 11 U.S. cities and clinicians should consider obtaining cultures and modifying empirical therapy to provide MRSA coverage.
Abstract: BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly recognized in infections among persons in the community without established risk factors for MRSA. METHODS We enrolled adult patients with acute, purulent skin and soft-tissue infections presenting to 11 university-affiliated emergency departments during the month of August 2004. Cultures were obtained, and clinical information was collected. Available S. aureus isolates were characterized by antimicrobial-susceptibility testing, pulsed-field gel electrophoresis, and detection of toxin genes. On MRSA isolates, we performed typing of the staphylococcal cassette chromosome mec (SCCmec), the genetic element that carries the mecA gene encoding methicillin resistance. RESULTS S. aureus was isolated from 320 of 422 patients with skin and soft-tissue infections (76 percent). The prevalence of MRSA was 59 percent overall and ranged from 15 to 74 percent. Pulsed-field type USA300 isolates accounted for 97 percent of MRSA isolates; 74 percent of these were a single strain (USA300-0114). SCCmec type IV and the Panton-Valentine leukocidin toxin gene were detected in 98 percent of MRSA isolates. Other toxin genes were detected rarely. Among the MRSA isolates, 95 percent were susceptible to clindamycin, 6 percent to erythromycin, 60 percent to fluoroquinolones, 100 percent to rifampin and trimethoprim-sulfamethoxazole, and 92 percent to tetracycline. Antibiotic therapy was not concordant with the results of susceptibility testing in 100 of 175 patients with MRSA infection who received antibiotics (57 percent). Among methicillin-susceptible S. aureus isolates, 31 percent were USA300 and 42 percent contained pvl genes. CONCLUSIONS MRSA is the most common identifiable cause of skin and soft-tissue infections among patients presenting to emergency departments in 11 U.S. cities. When antimicrobial therapy is indicated for the treatment of skin and soft-tissue infections, clinicians should consider obtaining cultures and modifying empirical therapy to provide MRSA coverage.

2,096 citations