Since the 1960s, methicillin-resistant Staphylococcus aureus (MRSA) has emerged, disseminated globally and become a leading cause of bacterial infections in both health-care and community settings. However, there is marked geographical variation in MRSA burden owing to several factors, including differences in local infection control practices and pathogen-specific characteristics of the circulating clones. Different MRSA clones have resulted from the independent acquisition of staphylococcal cassette chromosome mec (SCCmec), which contains genes encoding proteins that render the bacterium resistant to most β-lactam antibiotics (such as methicillin), by several S. aureus clones. The success of MRSA is a consequence of the extensive arsenal of virulence factors produced by S. aureus combined with β-lactam resistance and, for most clones, resistance to other antibiotic classes. Clinical manifestations of MRSA range from asymptomatic colonization of the nasal mucosa to mild skin and soft tissue infections to fulminant invasive disease with high mortality. Although treatment options for MRSA are limited, several new antimicrobials are under development. An understanding of colonization dynamics, routes of transmission, risk factors for progression to infection and conditions that promote the emergence of resistance will enable optimization of strategies to effectively control MRSA. Vaccine candidates are also under development and could become an effective prevention measure.

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Methicillin-resistant Staphylococcus aureus.

Background: Current evidence does not provide a clear definition of the association between methicillinresistant Staphylococcus aureus (MRSA) isolation and previous antibiotic use. A systematic review was performed to determine whether antibiotic exposure is a risk factor for the isolation of MRSA. Methods: MEDLINE and EMBASE databases were searched to identify studies published between 1976 and 2007 on the role of antibiotics as a risk factor for MRSA isolation in adult patients. The outcome of interest was MRSA isolation. Summary statistics were risk ratios (RR) comparing MRSA-positive patients to those without S. aureus isolation or with methicillin-susceptible S. aureus isolation. Results: Seventy-six studies, including a total of 24 230 patients, met the inclusion criteria. Antibiotic exposure was determined in the 126 + + 184 (mean + SD) days preceding MRSA isolation. The risk of acquiring MRSA was increased by 1.8-fold [95% confidence interval (CI), 1.7‐1.9; P < 0.001] in patients who had taken antibiotics. The RR for single classes of antibiotics was 3 (95% CI, 2.5‐3.5) for quinolones, 2.9 (95% CI, 2.4‐3.5) for glycopeptides, 2.2 (95% CI, 1.7‐2.9) for cephalosporins and 1.9 (95% CI, 1.7‐2.2) for other b-lactams. Significant heterogeneity was detected among studies. A regression analysis revealed that the heterogeneity was linked to the length of time in which antibiotic exposure was detected before MRSA isolation (more or less than 180 days).

Does antibiotic exposure increase the risk of methicillin-resistant Staphylococcus aureus (MRSA) isolation? A systematic review and meta-analysis

Staphylococcus aureus has been an important human pathogen throughout history and is currently a leading cause of bacterial infections worldwide. S. aureus has the unique ability to cause a continuum of diseases, ranging from minor skin infections to fatal necrotizing pneumonia. Moreover, the emergence of highly virulent, drug-resistant strains such as methicillin-resistant S. aureus in both healthcare and community settings is a major therapeutic concern. Neutrophils are the most prominent cellular component of the innate immune system and provide an essential primary defense against bacterial pathogens such as S. aureus. Neutrophils are rapidly recruited to sites of infection where they bind and ingest invading S. aureus, and this process triggers potent oxidative and non-oxidative antimicrobial killing mechanisms that serve to limit pathogen survival and dissemination. S. aureus has evolved numerous mechanisms to evade host defense strategies employed by neutrophils, including the ability to modulate normal neutrophil turnover, a process critical to the resolution of acute inflammation. Here we provide an overview of the role of neutrophils in host defense against bacterial pathogens and discuss strategies employed by S. aureus to circumvent neutrophil function.

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Neutrophils in innate host defense against Staphylococcus aureus infections

Staphylococcus aureus is a major cause of bacteremia, and S. aureus bacteremia is associated with higher morbidity and mortality, compared with bacteremia caused by other pathogens. The burden of S. aureus bacteremia, particularly methicillin-resistant S. aureus bacteremia, in terms of cost and resource use is high. The risk of infective endocarditis and of seeding to other metastatic foci increases the risk of mortality and raises the stakes for early, appropriate treatment. The incidence of S. aureus bacteremia and its complications has increased sharply in recent years because of the increased frequency of invasive procedures, increased numbers of immunocompromised patients, and increased resistance of S. aureus strains to available antibiotics. This changing epidemiology of S. aureus bacteremia, in combination with the inherent virulence of the pathogen, is driving an urgent need for improved strategies and better antibiotics to prevent and treat S. aureus bacteremia and its complications.

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Staphylococcus aureus Bacteremia: Epidemiology, Pathophysiology, and Management Strategies

https://www.id.theclinics.com/article/S0891-5520(08)00085-8/pdf

Host Defense and Pathogenesis in Staphylococcus aureus Infections

The virulence, antimicrobial resistance, and prevalence of S. aureus underscores the need for up-to-date and extensive insights regarding antimicrobial susceptibility trends. One approach to meet this need is analysis of clinical laboratory – based surveillance data. Data from The Surveillance Network-USA (TSN), an electronic surveillance network that collects microbiology data from 300 clinical microbiology laboratories across the United States, were used as the source for analysis that included prevalence of S. aureus in clinical specimens, MRSA and multi-drug resistance phenotype rates and trends according to patient location, geographic distributions, and specimen source. S. aureus was the most prevalent species isolated from inpatient specimens (18.7% of all bacterial isolates) and the second most prevalent (14.7%) from outpatient specimens. In March 2005 MRSA rates were 59.2%, 55%, and 47.9% for strains from non-ICU inpatients, ICU, and outpatients, respectively. This trend was noted in all nine US Bureau of Census regions and multi-drug resistance phenotypes (resistance to ≥ 3 non-beta-lactams) was common among both inpatient MRSA (59.9%) and outpatient MRSA (40.8%). Greater than 90% of multi-drug resistant MRSA were susceptible to trimethoprim-sulfamethoxazole, linezolid, and vancomycin. Prevalence of MRSA among both inpatient and outpatient specimens continues to increase with multi-drug resistance as a common phenotype. Continued emergence of outpatient MRSA that exhibit multi-drug resistant phenotypes has important implications for developing and evolving outpatient treatment guidelines.

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David A. Styers

Papers

Laboratory-based surveillance of current antimicrobial resistance patterns and trends among Staphylococcus aureus: 2005 status in the United States