high-throughput-identification-bacteria-repellent-polymers-for

High-throughput Identification of Bacteria Repellent Polymers for Medical Devices

Medical devices are often associated with hospital-acquired infections, which place enormous strain on patients and the healthcare system as well as ...

Royal Infirmary of Edinburgh

Ventilator-associated pneumonia (VAP) is the most commonly fatal nosocomial infection. Clinical diagnosis of VAP remains notoriously inaccurate. The hypothesis was tested that significantly augmented inflammatory markers distinguish VAP from conditions closely mimicking VAP.

Diagnostic importance of pulmonary interleukin-1beta and interleukin-8 in ventilator-associated pneumonia.

Critically ill patients are at heightened risk for nosocomial infections. The anaphylatoxin C5a impairs phagocytosis by neutrophils. However, the mechanisms by which this occurs and the relevance for acquisition of nosocomial infection remain undetermined. We aimed to characterize mechanisms by which C5a inhibits phagocytosis in vitro and in critically ill patients, and to define the relationship between C5a-mediated dysfunction and acquisition of nosocomial infection. In healthy human neutrophils, C5a significantly inhibited RhoA activation, preventing actin polymerization and phagocytosis. RhoA inhibition was mediated by PI3Kδ. The effects on RhoA, actin, and phagocytosis were fully reversed by GM-CSF. Parallel observations were made in neutrophils from critically ill patients, that is, impaired phagocytosis was associated with inhibition of RhoA and actin polymerization, and reversed by GM-CSF. Among a cohort of 60 critically ill patients, C5a-mediated neutrophil dysfunction (as determined by reduced CD88 expression) was a strong predictor for subsequent acquisition of nosocomial infection (relative risk, 5.8; 95% confidence interval, 1.5-22; P = .0007), and remained independent of time effects as assessed by survival analysis (hazard ratio, 5.0; 95% confidence interval, 1.3-8.3; P = .01). In conclusion, this study provides new insight into the mechanisms underlying immunocompromise in critical illness and suggests novel avenues for therapy and prevention of nosocomial infection.

C5a-mediated neutrophil dysfunction is RhoA-dependent and predicts infection in critically ill patients.

Ventilator-associated pneumonia is the most common intensive care unit-acquired infection. Although there is widespread consensus that evidenced-based interventions reduce the risk of ventilator-associated pneumonia, controversy has surrounded the importance of implementing them as a "bundle" of care. This study aimed to determine the effects of implementing such a bundle while controlling for potential confounding variables seen in similar studies.

Reducing ventilator-associated pneumonia in intensive care: impact of implementing a care bundle.

Student selected components (SSCs), at that time termed special study modules, were arguably the most innovative element in Tomorrow's Doctors (1993), the document from the General Medical Council that initiated the modernization of medical curricula in the UK. SSCs were proposed to make up one-third of the medical curriculum and provide students with choice, whilst allowing individual schools autonomy in how SSCs were utilized. In response, at the University of Edinburgh the undergraduate medical curriculum provides an integrated and sequential development and assessment of research skill learning outcomes, for all students in the SSC programme. The curriculum contains SSCs which provide choice to students in all 5 years. There are four substantial timetabled SSCs where students develop research skills in a topic and speciality of their choice. These SSCs are fully integrated and mapped with core learning outcomes and assessment, particularly with the 'Evidence-Based Medicine and Research' programme theme. These research skills are developed incrementally and applied fully in a research project in the fourth year. One-third of students also perform an optional intercalated one-year honours programme between years 2 and 3, usually across a wide range of honours schools at the biomedical science interface. Student feedback is insightful and demonstrates perceived attainment of research competencies. The establishment of these competencies is discussed in the context of enabling junior graduate doctors to be effective and confident at utilizing their research skills to effectively practice evidence-based medicine. This includes examining their own practice through clinical audit, developing an insight into the complexity of the evidence base and uncertainty, and also gaining a view into a career as a clinical academic.

An integrated model for developing research skills in an undergraduate medical curriculum: appraisal of an approach using student selected components.

Nosocomial infections due to bacteria have serious implications on the health and recovery of patients in a variety of medical scenarios. Since bacterial contamination on medical devices contributes to the majority of nosocomical infections, there is a need for redesigning the surfaces of medical devices, such as catheters and tracheal tubes, to resist the binding of bacteria. In this work, polyurethanes and polyacrylates/acrylamides, which resist binding by the major bacterial pathogens underpinning implant-associated infections, were identified using high-throughput polymer microarrays. Subsequently, two 'hit' polymers, PA13 (poly(methylmethacrylate-co-dimethylacrylamide)) and PA515 (poly(methoxyethylmethacrylate-co-diethylaminoethylacrylate-co-methylmethacrylate)), were used to coat catheters and substantially shown to decrease binding of a variety of bacteria (including isolates from infected endotracheal tubes and heart valves from intensive care unit patients). Catheters coated with polymer PA13 showed up to 96% reduction in bacteria binding in comparison to uncoated catheters.

Bacteria repelling poly(methylmethacrylate-co-dimethylacrylamide) coatings for biomedical devices†Electronic supplementary information (ESI) available: Polymer microarray screening, including analysis of bacterial adhesion by fluorescence microscopy and SEM, and chemical composition of bacteria repelling polymers identified in the screen; polymer synthesis and characterisation; preparation of catheter pieces and solvent studies, and details for confocal imaging/analysis. See DOI: 10.1039/c4tb01129eClick here for additional data file.

Infections arising from contaminated medical devices are a serious global issue, contributing to antibiotic resistance and imposing significant strain on healthcare systems. Since the majority of medical device-associated infections are biofilm related, efforts are being made to generate either bacteria-repellent or antibacterial coatings aimed at preventing bacterial colonisation. Here, we utilise a nanocapsule mediated slow release of a natural antimicrobial to improve the performance of a bacteria repellent polymer coating. Poly(lauryl acrylate) nanocapsules containing eugenol (4-allyl-2-methoxyphenol) were prepared and entrapped within a interpenetrating network designed to repel bacteria. When coated on a catheter and an endotracheal tube, this hemocompatible system allowed slow-release of eugenol, resulting in notable reduction in surface-bound Klebsiella pneumoniae and methicillin resistant Staphylococcus aureus.

Article	Year
Diagnostic importance of pulmonary interleukin-1beta and interleukin-8 in ventilator-associated pneumonia. Thorax\| PubMed ID: 19825784	2010
C5a-mediated neutrophil dysfunction is RhoA-dependent and predicts infection in critically ill patients. Blood\| PubMed ID: 21292772	2011
Reducing ventilator-associated pneumonia in intensive care: impact of implementing a care bundle. Critical care medicine\| PubMed ID: 21666444	2011
An integrated model for developing research skills in an undergraduate medical curriculum: appraisal of an approach using student selected components. Perspectives on medical education\| PubMed ID: 24037741	2013
Bacteria repelling poly(methylmethacrylate-co-dimethylacrylamide) coatings for biomedical devices†Electronic supplementary information (ESI) available: Polymer microarray screening, includin... Journal of materials chemistry. B, Materials for biology and medicine\| PubMed ID: 25580245	2014
Fortified interpenetrating polymers - bacteria resistant coatings for medical devices. Journal of materials chemistry. B, Materials for biology and medicine\| PubMed ID: 27746915	2016

David G. Swann

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