Pseudomonas aeruginosa infection in augmented care: the molecular ecology and transmission dynamics in four large UK hospitals.

Background: Pseudomonas aeruginosa is a common opportunistic pathogen and molecular typing in outbreaks has linked patient acquisition to contaminated hospital water systems.

Aim: To elucidate the role of P. aeruginosa transmission rates in non-outbreak augmented care settings in the UK.

Loss of microbial diversity and pathogen domination of the gut microbiota in critically ill patients.

Among long-stay critically ill patients in the adult intensive care unit (ICU), there are often marked changes in the complexity of the gut microbiota. However, it remains unclear whether such patients might benefit from enhanced surveillance or from interventions targeting the gut microbiota or the pathogens therein. We therefore undertook a prospective observational study of 24 ICU patients, in which serial faecal samples were subjected to shotgun metagenomic sequencing, phylogenetic profiling and microbial genome analyses.

Violet-Blue Light Arrays at 405 Nanometers Exert Enhanced Antimicrobial Activity for Photodisinfection of Monomicrobial Nosocomial Biofilms.

Light-emitting diodes (LEDs) demonstrate therapeutic effects for a range of biomedical applications, including photodisinfection. Bands of specific wavelengths (centered at 405 nm) are reported to be the most antimicrobial; however, there remains no consensus on the most effective irradiation parameters for optimal photodisinfection. The aim of this study was to assess decontamination efficiency by direct photodisinfection of monomicrobial biofilms using a violet-blue light (VBL) single-wavelength array (SWA) and multiwavelength array (MWA).

Schistosome Interactions within the Schistosoma haematobium Group, Malawi.

Molecular analysis of atypical schistosome eggs retrieved from children in Malawi revealed genetic interactions occurring between human (Schistosoma haematobium) and livestock (S. mattheei and S. bovis) schistosome species.

The potential of visible blue light (405 nm) as a novel decontamination strategy for carbapenemase-producing enterobacteriaceae (CPE).

Background: Carbapenemase-producing (CPE) pose a considerable threat to modern medicine. New treatment options and methods to limit spread need to be investigated. Blue light (BL) is intrinsically antimicrobial, and we have previously demonstrated significant antimicrobial effects on biofilms of a panel of isolates, including two CPEs.

Whole genome sequencing of toxigenic Clostridium difficile in asymptomatic carriers: insights into possible role in transmission.

Background: Estimates of the prevalence of asymptomatically carried Clostridium difficile in elderly patients in long-term care range from 0% to 51%. Asymptomatic carriage is possibly a risk factor for the development of infection, and there is ongoing debate surrounding the role of asymptomatic carriage in transmission.

Aim: To investigate the prevalence of asymptomatic carriage amongst patients residing in intermediate care (bedded) facilities (ICBFs), and to investigate whether asymptomatically carried C.

Use of an engineered honey to eradicate preformed biofilms of important wound pathogens: an in vitro study.

Objective: We previously reported on the ability of SurgihoneyRO (SHRO), an engineered honey, to prevent biofilm formation in vitro, but data were lacking regarding the activity against preformed biofilms. This study aims to assess whether SHRO has any antibacterial activity against mature, preformed biofilms and whether there is any evidence to support the observed clinical effectiveness when SHRO has been used anecdotally on acute and chronic wounds where biofilm is most likely present.

Method: We tested the in vitro antibacterial activity of SHRO against the mature biofilms of 16 clinically relevant wound pathogens, in terms of impacts on biofilm seeding and biofilm biomass.

A systematic review of quantitative burn wound microbiology in the management of burns patients.

Background: The early diagnosis of infection or sepsis in burns are important for patient care. Globally, a large number of burn centres advocate quantitative cultures of wound biopsies for patient management, since there is assumed to be a direct link between the bioburden of a burn wound and the risk of microbial invasion. Given the conflicting study findings in this area, a systematic review was warranted.

The contribution of leucocytes to the antimicrobial activity of platelet-rich plasma preparations: A systematic review.

The infection of a wound is one of the major contributors to delays in healing and tissue regeneration. As multi-drug resistance to antibiotics is becoming a serious threat, research in this field has focused on finding new agents and strategies to fight infection and additionally to reduce healing times. The topical use of autologous Platelet Rich Plasma (PRP) as a biological accelerator of the healing process, has been safely used as a form of treatment for wounds since the 1990s.

Reactive oxygen: A novel antimicrobial mechanism for targeting biofilm-associated infection.

Reactive oxygen species (ROS) is a novel therapeutic strategy for topical or local application to wounds, mucosa or internal structures where there may be heavy bacterial bioburden with biofilm and chronic inflammation. Bacterial biofilms are a significant problem in clinical settings owing to their increased tolerance towards conventionally prescribed antibiotics and their propensity for selection of further antibacterial resistance. There is therefore a pressing need for the development of alternative therapeutic strategies that can improve antibiotic efficacy towards biofilms.

Antimicrobial peptide coatings for hydroxyapatite: electrostatic and covalent attachment of antimicrobial peptides to surfaces.

The interface between implanted devices and their host tissue is complex and is often optimized for maximal integration and cell adhesion. However, this also gives a surface suitable for bacterial colonization. We have developed a novel method of modifying the surface at the material-tissue interface with an antimicrobial peptide (AMP) coating to allow cell attachment while inhibiting bacterial colonization.

Antibacterial Activity of Blue Light against Nosocomial Wound Pathogens Growing Planktonically and as Mature Biofilms.

Unlabelled: The blue wavelengths within the visible light spectrum are intrinisically antimicrobial and can photodynamically inactivate the cells of a wide spectrum of bacteria (Gram positive and negative) and fungi. Furthermore, blue light is equally effective against both drug-sensitive and -resistant members of target species and is less detrimental to mammalian cells than is UV radiation. Blue light is currently used for treating acnes vulgaris and Helicobacter pylori infections; the utility for decontamination and treatment of wound infections is in its infancy.

Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01.

Background: Models of controlled human malaria infection (CHMI) initiated by mosquito bite have been widely used to assess efficacy of preerythrocytic vaccine candidates in small proof-of-concept phase 2a clinical trials. Efficacy testing of blood-stage malaria parasite vaccines, however, has generally relied on larger-scale phase 2b field trials in malaria-endemic populations. We report the use of a blood-stage P.

In vitro activity of an engineered honey, medical-grade honeys, and antimicrobial wound dressings against biofilm-producing clinical bacterial isolates.

Objective: Honey is recognised to be a good topical wound care agent owing to a broad-spectrum of antimicrobial activity combined with healing properties. Surgihoney RO (SH1) is a product based on honey that is engineered to produce enhanced reactive oxygen species (ROS) and has been reported to be highly antimicrobial. The objective was to investigate the ability of the engineered honey and its comparators to prevent biofilm formation in vitro.

Protocol for a systematic review of quantitative burn wound microbiology in the management of burns patients.

Background: Sepsis from burn injuries can result from colonisation of burn wounds, especially in large surface area burns. Reducing bacterial infection will reduce morbidity and mortality, and mortality for severe burns can be as high as 15 %. There are various quantitative and semi-quantitative techniques to monitor bacterial load on wounds.

The Antibacterial Activity of Acetic Acid against Biofilm-Producing Pathogens of Relevance to Burns Patients.

Introduction: Localised infections, and burn wound sepsis are key concerns in the treatment of burns patients, and prevention of colonisation largely relies on biocides. Acetic acid has been shown to have good antibacterial activity against various planktonic organisms, however data is limited on efficacy, and few studies have been performed on biofilms.

Objectives: We sought to investigate the antibacterial activity of acetic acid against important burn wound colonising organisms growing planktonically and as biofilms.

Antimicrobial dressings: Comparison of the ability of a panel of dressings to prevent biofilm formation by key burn wound pathogens.

Unlabelled: Antimicrobial medicated dressings (AMD) are often used to reduce bacterial infection of burns and other wounds. However, there is limited literature regarding comparative efficacies to inform effective clinical decision making.

Objectives: Following on from a previous study where we demonstrated good antibiofilm properties of acetic acid (AA), we assessed and compared the in vitro anti-biofilm activity of a range of AMDs and non-AMDs to AA.

Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure.

The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite--MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost.

Analysis of human B-cell responses following ChAd63-MVA MSP1 and AMA1 immunization and controlled malaria infection.

Acquisition of non-sterilizing natural immunity to Plasmodium falciparum malaria has been shown in low transmission areas following multiple exposures. However, conflicting data from endemic areas suggest that the parasite may interfere with the induction of effective B-cell responses. To date, the impact of blood-stage parasite exposure on antigen-specific B cells has not been reported following controlled human malaria infection (CHMI).

Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation.

Induction of antigen-specific CD8(+) T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8(+) T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/10(6) peripheral blood mononuclear cells) to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays time to patency through substantial reduction of liver-stage parasite burden in five more (5/14, 36%), P=0.

Universal extraction method for gastrointestinal pathogens.

A universal stool extraction method for recovery of nucleic acids (NAs) from gastrointestinal pathogens was developed to support rapid diagnostics for the London 2012 Olympics. The method involved mechanical disruption (bead beating) of the stools, followed by automated extraction and detection using real-time PCR. This method had been used extensively in the Second Infectious Intestinal Disease Study (IID2) for the isolation of NA from bacteria and parasites (and was effective for the robust recovery of Cryptosporidium spp.

Assessment of immune interference, antagonism, and diversion following human immunization with biallelic blood-stage malaria viral-vectored vaccines and controlled malaria infection.

Overcoming antigenic variation is one of the major challenges in the development of an effective vaccine against Plasmodium falciparum, a causative agent of human malaria. Inclusion of multiple Ag variants in subunit vaccine candidates is one strategy that has aimed to overcome this problem for the leading blood-stage malaria vaccine targets, that is, merozoite surface protein 1 (MSP1) and apical membrane Ag 1 (AMA1). However, previous studies, utilizing malaria Ags, have concluded that inclusion of multiple allelic variants, encoding altered peptide ligands, in such a vaccine may be detrimental to both the priming and in vivo restimulation of Ag-experienced T cells.

ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans.

The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults.

Changes in causes of acute gastroenteritis in the United Kingdom over 15 years: microbiologic findings from 2 prospective, population-based studies of infectious intestinal disease.

Background: Large-scale, prospective studies of infectious intestinal disease (IID) in developed countries are uncommon. Two studies of IID incidence and etiology have been conducted in the United Kingdom: the Infectious Intestinal Disease Study in England (IID1) in 1993-1996 and the Second Study of Infectious Intestinal Disease in the Community (IID2) in 2008-2009. We examined changes in etiology and diagnostic yield of IID cases over 15 years.