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Background Identifying and tackling the social determinants of infectious diseases has become a public health priority following the recognition that individuals with lower socioeconomic status are disproportionately affected by infectious diseases. In many parts of the world, epidemiologically and genotypically defined community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged to become frequent causes of hospital infection. The aim of this study was to use spatial models with adjustment for area-level hospital attendance to determine the transmission niche of genotypically defined CA- and health-care-associated (HA)-MRSA strains across a diverse region of South East London and to explore a potential link between MRSA carriage and markers of social and material deprivation. Methods and Findings This study involved spatial analysis of cross-sectional data linked with all MRSA isolates identified by three National Health Service (NHS) microbiology laboratories between 1 November 2011 and 29 February 2012. The cohort of hospital-based NHS microbiology diagnostic services serves 867,254 usual residents in the Lambeth, Southwark, and Lewisham boroughs in South East London, United Kingdom (UK). Isolates were classified as HA- or CA-MRSA based on whole genome sequencing. All MRSA cases identified over 4 mo within the three-borough catchment area (n = 471) were mapped to small geographies and linked to area-level aggregated socioeconomic and demographic data. Disease mapping and ecological regression models were used to infer the most likely transmission niches for each MRSA genetic classification and to describe the spatial epidemiology of MRSA in relation to social determinants. Specifically, we aimed to identify demographic and socioeconomic population traits that explain cross-area extra variation in HA- and CA-MRSA relative risks following adjustment for hospital attendance data. We explored the potential for associations with the English Indices of Deprivation 2010 (including the Index of Multiple Deprivation and several deprivation domains and subdomains) and the 2011 England and Wales census demographic and socioeconomic indicators (including numbers of households by deprivation dimension) and indicators of population health. Both CA-and HA-MRSA were associated with household deprivation (CA-MRSA relative risk [RR]: 1.72 [1.03-2.94]; HA-MRSA RR: 1.57 [1.06-2.33]), which was correlated with hospital attendance (Pearson correlation coefficient [PCC] = 0.76). HA-MRSA was also associated with poor health (RR: 1.10 [1.01-1.19]) and residence in communal care homes (RR: 1.24 [1.12-1.37]), whereas CA-MRSA was linked with household overcrowding (RR: 1.58 [1.04-2.41]) and wider barriers, which represent a combined score for household overcrowding, low income, and homelessness (RR: 1.76 [1.16-2.70]). CA-MRSA was also associated with recent immigration to the UK (RR: 1.77 [1.19-2.66]). For the area-level variation in RR for CA-MRSA, 28.67% was attributable to the spatial arrangement of target geographies, compared with only 0.09% for HA-MRSA. An advantage to our study is that it provided a representative sample of usual residents receiving care in the catchment areas. A limitation is that relationships apparent in aggregated data analyses cannot be assumed to operate at the individual level. Conclusions There was no evidence of community transmission of HA-MRSA strains, implying that HA-MRSA cases identified in the community originate from the hospital reservoir and are maintained by frequent attendance at health care facilities. In contrast, there was a high risk of CA-MRSA in deprived areas linked with overcrowding, homelessness, low income, and recent immigration to the UK, which was not explainable by health care exposure. Furthermore, areas adjacent to these deprived areas were themselves at greater risk of CA-MRSA, indicating community transmission of CA-MRSA. This ongoing community transmission could lead to CA-MRSA becoming the dominant strain types carried by patients admitted to hospital, particularly if successful hospital-based MRSA infection control programmes are maintained. These results suggest that community infection control programmes targeting transmission of CA-MRSA will be required to control MRSA in both the community and hospital. These epidemiological changes will also have implications for effectiveness of risk-factor-based hospital admission MRSA screening programmes., Introduction In recent years, systematic health inequalities and the uneven distribution of adverse health outcomes have been found to affect a wide array of infectious diseases, not just chronic diseases [...]

The article discusses research which investigated the administration of intravenous immunoglobulin (IVIG) in a rabbit model of necrotizing pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). Topics explored include the capability of human polyclonal antibodies in IVIG to neutralize MRSA-associated toxins, the survival outcomes recorded following treatment, and clinical information on the pathogenesis of MRSA pneumonia.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is epidemic in the United States, even rivaling HIV/AIDS in its public health impact. The pandemic clone USA300, like other CA-MRSA strains, expresses Panton-Valentine leukocidin (PVL), a pore-forming toxin that targets polymorphonuclear leukocytes (PMNs). PVL is thought to play a key role in the pathogenesis of necrotizing pneumonia, but data from rodent infection models are inconclusive. Rodent PMNs are less susceptible than human PMNs to PVL-induced cytolysis, whereas rabbit PMNs, like those of humans, are highly susceptible to PVL-induced cytolysis. This difference in target cell susceptibility could affect results of experimental models. Therefore, we developed a rabbit model of necrotizing pneumonia to compare the virulence of a USA300 wild-type strain with that of isogenic PVL-deletion mutant and -complemented strains. PVL enhanced the capacity of USA300 to cause severe lung necrosis, pulmonary edema, alveolar hemorrhage, hemoptysis, and death, hallmark clinical features of fatal human necrotizing pneumonia. Purified PVL instilled directly into the lung caused lung inflammation and injury by recruiting and lysing PMNs, which damage the lung by releasing cytotoxic granule contents. These findings provide insights, into the mechanism of PVL-induced lung injury and inflammation and demonstrate the utility of the rabbit for studying PVLmediated pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that hospital transmission of methicillin-resistant Staphylococcus aureus (MRSA) is uncommon in UK centers that have implemented sustained infection control programs. We investigated whether a healthcare-network analysis could shed light on transmission paths currently sustaining MRSA levels in UK hospitals., Methods: A cross-sectional observational study was performed in 2 National Health Service hospital groups and a general district hospital in Southeast London. All MRSA patients identified at inpatient, outpatient, and community settings between 1 November 2011 and 29 February 2012 were included. We identified genetically defined MRSA transmission clusters in individual hospitals and across the healthcare network, and examined genetic differentiation of sequence type (ST) 22 MRSA isolates within and between hospitals and inpatient or outpatient and community settings, as informed by average and median pairwise single-nucleotide polymorphisms (SNPs) and SNP-based proportions of nearly identical isolates., Results: Two hundred forty-eight of 610 (40.7%) MRSA patients were linked in 90 transmission clusters, of which 27 spanned multiple hospitals. Analysis of a large 32 patient ST22-MRSA cluster showed that 26 of 32 patients (81.3%) had multiple contacts with one another during ward stays at any hospital. No residential, outpatient, or significant community healthcare contacts were identified. Genetic differentiation between ST22 MRSA inpatient isolates from different hospitals was less than between inpatient isolates from the same hospitals (P ≤ .01)., Conclusions: There is evidence of frequent ward-based transmission of MRSA brought about by frequent patient admissions to multiple hospitals. Limiting in-ward transmission requires sharing of MRSA status data between hospitals., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) have emerged globally and have been associated with more severe disease than healthcare-associated MRSA (HA-MRSA). The purpose of this study was to determine whether laboratory measures of virulence can distinguish dominant CA-MRSA clones from HA-MRSA clones. We compared the production of phenol-soluble modulins (PSMs) and ability to kill Galleria mellonella caterpillars for a range of CA- and HA-MRSA strains. Twenty-two HA-MRSA strains [ST22-IV (EMRSA-15), ST36-II (EMRSA-16) and ST239-III] and 26 CA-MRSA strains [ST1-IV (PVL+ USA400), ST1-IV (PVL-), ST8-IV (USA300), ST22-IV (PVL+), ST30-IV, ST59-IV and ST80-IV] were analysed. PSM production was measured using and compared using t-tests and ANOVA. A G mellonella (caterpillar) pathogenicity model was performed, and differences were compared using survival analysis and the log-rank test. There was no significant difference in overall PSM production between HA and CA strains (P=0.090), but there was significant variation between clones (P=0.003). G. mellonella caterpillar killing varied significantly by clone (P<0.001), and overall killing was greater for HA compared with CA clones (P=0.007). The increased acute virulence phenotype of CA-MRSA clones in humans is not associated with increased PSM production in vitro or increased killing in an in vivo caterpillar pathogenicity model.