Methicillin-resistant Staphylococcus aureus bacteremia:epidemiology, outcome, and laboratory characteristics in a tertiary referral center in the UK

Objective: To analyze the recent epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in a UK tertiary referral center. Methods: We collected epidemiological and laboratory data on all cases of MRSA bacteremia from September 1, 2005 to December 31, 2007. Results: There were 195 clinically significant episodes. Most were hospital-acquired. Only one episode occurred in patients without a history of hospital admission in the previous 12 months. An intravascular device was the most common focus of infection (37%), with no identifiable source found in 35% of episodes. Twenty-eight percent of patients died within 30 days of bacteremia. Mortality was significantly higher in the absence of an identifiable focus. Failure to include an antibiotic active against MRSA in the empirical treatment was only significantly associated with death in patients showing signs of hemodynamic instability (p < 0.001). No isolates had a minimum inhibitory concentration to vancomycin above 1.5. mg/l and no heteroresistance to glycopeptide antibiotics (heteroresistant vancomycin-intermediate Staphylococcus aureus; hVISA) was detected. All isolates were sensitive to daptomycin, tigecycline, and linezolid. Conclusions: Despite improvement in infection control measures, medical devices remain the most common source of infection. Inappropriate empirical antibiotic usage is associated with a poor outcome in patients with signs of severe sepsis. Susceptibility to glycopeptides and newer antibiotics remains good. © 2010 International Society for Infectious Diseases.

Description and critical appraisal of principal components analysis (PCA) methodology applied to pulsed-field gel electrophoresis profiles of methicillin-resistant Staphylococcus aureus isolates

Principal components analysis (PCA) has been described for over 50 years; however, it is rarely applied to the analysis of epidemiological data. In this study PCA was critically appraised in its ability to reveal relationships between pulsed-field gel electrophoresis (PFGE) profiles of methicillin- resistant Staphylococcus aureus (MRSA) in comparison to the more commonly employed cluster analysis and representation by dendrograms. The PFGE type following SmaI chromosomal digest was determined for 44 multidrug-resistant hospital-acquired methicillin-resistant S. aureus (MR-HA-MRSA) isolates, two multidrug-resistant community-acquired MRSA (MR-CA-MRSA), 50 hospital-acquired MRSA (HA-MRSA) isolates (from the University Hospital Birmingham, NHS Trust, UK) and 34 community-acquired MRSA (CA-MRSA) isolates (from general practitioners in Birmingham, UK). Strain relatedness was determined using Dice band-matching with UPGMA clustering and PCA. The results indicated that PCA revealed relationships between MRSA strains, which were more strongly correlated with known epidemiology, most likely because, unlike cluster analysis, PCA does not have the constraint of generating a hierarchic classification. In addition, PCA provides the opportunity for further analysis to identify key polymorphic bands within complex genotypic profiles, which is not always possible with dendrograms. Here we provide a detailed description of a PCA method for the analysis of PFGE profiles to complement further the epidemiological study of infectious disease. © 2005 Elsevier B.V. All rights reserved.

Molecular analysis of methicillin-resistant Staphylococcus aureus reveals an absence of plasmid DNA in multidrug-resistant isolates

The number, diversity and restriction enzyme fragmentation patterns of plasmids harboured by 44 multidrug-resistant hospital-acquired methicillin-resistant Staphylococcus aureus (MR-HA-MRSA) isolates, two multidrug-resistant community-acquired MRSA (MR-CA-MRSA), 50 hospital-acquired MRSA (HA-MRSA) isolates (from the University Hospital Birmingham, NHS Trust, UK) and 34 community-acquired MRSA (CA-MRSA) isolates (from general practitioners in Birmingham, UK) were compared. In addition, pulsed-field gel electrophoresis (PFGE) type following SmaI chromosomal digest and SCCmec element type assignment were ascertained for each isolate. All MR-HA-MRSA and MR-CA-MRSA isolates possessed the type II SCCmec, harboured no plasmid DNA and belonged to one of five PFGE types. Forty-three out of 50 HA-MRSA isolates and all 34 CA-MRSA isolates possessed the type IV SCCmec and all but 10 of the type IV HA-MRSA isolates and nine CA-MRSA isolates carried one or two plasmids. The 19 non-multidrug-resistant isolates (NMR) that did not harbour plasmids were only resistant to methicillin whereas all the NMR isolates harbouring at least one plasmid were resistant to at least one additional antibiotic. We conclude that although plasmid carriage plays an important role in antibiotic resistance, especially in NMR-HA-MRSA and CA-MRSA, the multidrug resistance phenotype from HA-MRSA is not associated with increased plasmid carriage and indeed is characterised by an absence of plasmid DNA. © 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

Epidemiology of community-acquired meticillin-resistant Staphylococcus aureus obtained from the UK West Midlands region

Between January 2005 and December 2005, 199 meticillin-resistant Staphylococcus aureus (MRSA) isolates were obtained from nonhospitalised patients presenting skin and soft tissue infections to local general practitioners. The study area incorporated 57 surgeries from three Primary Care Trusts in the Lichfield, Tamworth, Burntwood, North and East Birmingham regions of Central England, UK. Following antibiotic susceptibility testing, pulsed-field gel electrophoresis, Panton-Valentine leukocidin gene detection and SCCmec element assignment, 95% of the isolates were shown to be related to hospital epidemic strains EMRSA-15 and EMRSA-16. In total 87% of the isolate population harboured SCCmec IV, 9% had SCCmec II and 4% were identified as carrying novel SCCmec IIIa-mecI. When mapped to patient home postcode, a diverse distribution of isolates harbouring SCCmec II and SCCmec IV was observed; however, the majority of isolates harbouring SCCmec IIIa-mecI were from patients residing in the north-west of the study region, highlighting a possible localised clonal group. Transmission of MRSA from the hospital setting into the surrounding community population, as demonstrated by this study, warrants the need for targeted patient screening and decolonisation in both the clinical and community environments.

Visual function and subjective quality of life compared in subjects with acquired macular disease

PURPOSE: To determine the objective measures of visual function that are most relevant to subjective quality of vision and perceived reading ability in patients with acquired macular disease. METHODS: Twenty-eight patients with macular disease underwent a comprehensive assessment of visual function. The patients also completed a vision-related quality-of-life questionnaire that included a section of general questions about perceived visual performance and a section with specific questions on reading. RESULTS: Results of all tests of vision correlated highly with reported vision-related quality-of-life impairment. Low-contrast tests explained most of the variance in self-reported problems with reading. Text-reading speed correlated highly with overall concern about vision. CONCLUSIONS: Reading performance is strongly associated with vision-related quality of life. High-contrast distance acuity is not the only relevant measure of visual function in relation to the perceived visual performance of a patient with macular disease. The results suggest the importance of print contrast, even over print size, in reading performance in patients with acquired macular disease.

Spatial aspects of MRSA epidemiology:A case study using stochastic simulation, kernel estimation and SaTScan

The identification of disease clusters in space or space-time is of vital importance for public health policy and action. In the case of methicillin-resistant Staphylococcus aureus (MRSA), it is particularly important to distinguish between community and health care-associated infections, and to identify reservoirs of infection. 832 cases of MRSA in the West Midlands (UK) were tested for clustering and evidence of community transmission, after being geo-located to the centroids of UK unit postcodes (postal areas roughly equivalent to Zip+4 zip code areas). An age-stratified analysis was also carried out at the coarser spatial resolution of UK Census Output Areas. Stochastic simulation and kernel density estimation were combined to identify significant local clusters of MRSA (p<0.025), which were supported by SaTScan spatial and spatio-temporal scan. In order to investigate local sampling effort, a spatial 'random labelling' approach was used, with MRSA as cases and MSSA (methicillin-sensitive S. aureus) as controls. Heavy sampling in general was a response to MRSA outbreaks, which in turn appeared to be associated with medical care environments. The significance of clusters identified by kernel estimation was independently supported by information on the locations and client groups of nursing homes, and by preliminary molecular typing of isolates. In the absence of occupational/ lifestyle data on patients, the assumption was made that an individual's location and consequent risk is adequately represented by their residential postcode. The problems of this assumption are discussed, with recommendations for future data collection.

Varieties of acquired phonological dyslexia

The existence of different varieties of the acquired reading disorder termed "phonological dyslexia" is demonstrated in this thesis. The data are interpreted in terms of an information-processing model of normal reading which postulates autonomous routes for pronouncing lexical and non-lexical items and identifies a number of separable sub-processes within both lexical and non-lexical routes. A case study approach is used and case reports on ten patients who have particular difficulty in processing non-lexical stimuli following cerebral insult are presented, Chapters 1 and 2 describe the theoretical background to the investigation. Cognitive models of reading are examined in Chapter 1 and the theoretical status of the current taxonomy of the acquired dyslexias discussed in relation to the models. In Chapter 2 the symptoms associated with phonological dyslexia are discussed both in terms of the theoretical models and in terms of the cosistency with which they are reported to occur in clinical studies. Published cases of phonological dyslexia are reviewed. Chapter 3 describes the tests administered and the analysis of error responses. The majority of tests require reading aloud of single lexical or non-lexical items and investigate the effect of different variables on reading performance. Chapter 4 contains the case reports. The final chapter summarises the different patterns of reading behaviour observed. The theoretical model predicts the selective impairment of subsystems within the phonological route. The data provide evidence of such selective impairment. It is concluded that there are different varieties of phonological dyslexia corresponding to the different loci of impairment within the phonological route. It is also concluded that the data support the hypothesis that there are two lexical routes. A further subdivision of phonological dyslexia is made on the basis of selective impairment of the direct or lexical-semantic routes.

Anti-bacterial skin disinfectants in the reduction of methicillin resistant staphylococcus aureus (MRSA) skin colonisation

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Novel anti-bacterials against MRSA:Synthesis of focussed combinatorial libraries of tri-substituted 2(5H)-furanones

Mucobromic and mucochloric acid were used as building blocks for the construction of a chemical combinatorial library of 3,4,5-trisubstituted 2(5H)-furanones. With these 2 butenolide building blocks, and eight alcohols a sublibrary of 16 dihalogenated 5-alkoxy-2(5H)-furanones was prepared. This sublibrary of 5-alkoxylated furanones was reacted with 16 amines generating a full size focussed combinatorial library of 256 individual compounds. This three dimensional combinatorial library of 3-halogen-4-amino-5-alkoxy-2(5H)-furanones was prepared around the benzimidazolyl furanone lead structure by applying a solution phase combinatorial chemistry concept. Typical representatives of the library were purified and fully characterized and one x-ray structures was recorded, additionally. The 3-bromo-4-benzimizazolyl-5-methoxy-2(5H)furanone, Br-A-l, showed an MIC of 8 μg/ml against the multiresistant Staphylococcus aureus ( MRSA). © 2006 Bentham Science Publishers Ltd.

A knowledge driven approach towards the validation of externally acquired traceability datasets in supply chain business processes

The sharing of near real-time traceability knowledge in supply chains plays a central role in coordinating business operations and is a key driver for their success. However before traceability datasets received from external partners can be integrated with datasets generated internally within an organisation, they need to be validated against information recorded for the physical goods received as well as against bespoke rules defined to ensure uniformity, consistency and completeness within the supply chain. In this paper, we present a knowledge driven framework for the runtime validation of critical constraints on incoming traceability datasets encapuslated as EPCIS event-based linked pedigrees. Our constraints are defined using SPARQL queries and SPIN rules. We present a novel validation architecture based on the integration of Apache Storm framework for real time, distributed computation with popular Semantic Web/Linked data libraries and exemplify our methodology on an abstraction of the pharmaceutical supply chain.

Addition of PLA2 to CRP enhances sepsis diagnosis

Letter to the Editor refers to: Fredrikke Christie Knudtzen, Stig Lønberg Nielsen, Kim Oren Gradel, Annmarie Touborg Lassen, Hans Jørn Kolmos, Thøger Gorm Jensen, Pernille Just Vinholt, Court Pedersen, Characteristics of patients with community-acquired bacteremia who have low levels of C-reactive protein (≤20 mg/L), Journal of Infection, Volume 68, Issue 2, February 2014, Pages 149-155