A randomized controlled trial of tea tree oil (5%) body wash versus standard body wash to prevent colonization with methicillin-resistant Staphylococcus aureus (MRSA) in critically ill adults: research protocol

Background
Over the past ten years MRSA has become endemic in hospitals and is associated with increased healthcare costs. Critically ill patients are most at risk, in part because of the number of invasive therapies that they require in the intensive care unit (ICU). Washing with 5% tea tree oil (TTO) has been shown to be effective in removing MRSA on the skin. However, to date, no trials have evaluated the potential of TTO body wash to prevent MRSA colonization or infection. In addition, detecting MRSA by usual culture methods is slow. A faster method using a PCR assay has been developed in the laboratory, but requires evaluation in a large number of patients.

Methods/Design
This study protocol describes the design of a multicentre, phase II/III prospective open-label randomized controlled clinical trial to evaluate whether a concentration of 5% TTO is effective in preventing MRSA colonization in comparison with a standard body wash (Johnsons Baby Softwash) in the ICU. In addition we will evaluate the cost-effectiveness of TTO body wash and assess the effectiveness of the PCR assay in detecting MRSA in critically ill patients. On admission to intensive care, swabs from the nose and groin will be taken to screen for MRSA as per current practice. Patients will be randomly assigned to be washed with the standard body wash or TTO body wash. On discharge from the unit, swabs will be taken again to identify whether there is a difference in MRSA colonization between the two groups.

Discussion
If TTO body wash is found to be effective, widespread implementation of such a simple colonization prevention tool has the potential to impact on patient outcomes, healthcare resource use and patient confidence both nationally and internationally.

Trial Registration
[ISRCTN65190967]

Plasmid DNA analysis of Staphylococcus epidermidis isolated from blood and colonization cultures in very low birth weight neonates

We prospectively studied the course of colonization and sepsis with Staphylococcus epidermidis among 29 very low birth weight neonates undergoing prolonged umbilical catheterization. S. epidermidis bacteremia occurred in 7 patients. In 6 bacteremia was preceded by positive colonization cultures. Isolates obtained from nares, base of umbilicus, umbilical catheter entry sites, catheter tips and blood were examined for plasmid DNA profiles. In 4 patients the plasmid profiles of the catheter entry site isolates were identical with those of the blood isolates. In the other 3 bacteremic patients plasmid profiles of the catheter entry site and blood isolates were different. No correlation was observed in the plasmid DNA patterns of isolates obtained from catheter tip cultures as compared to the corresponding blood cultures. The blood isolates from bacteremic patients had different plasmid profiles.

The Influence of Aspect on the Biological Colonization of Stone in Northern Ireland.

The rate and type of biological colonization of stone is influenced by a wide array of environmental factors in addition to substrate characteristics. A series of experiments was designed to compare the rate and type of biological colonization of stone at varying locations over a 21-month time period. Exposure
trials were set up at nine different sites across Northern Ireland that covered a wide variety of environmental conditions. To determine aspect-related differences in colonization, blocks of Peakmoor sandstone and Portland limestone were placed on the north- and south-facing sides of purpose-designed exposure racks. Colorimetry and visual analysis were carried out on collected samples at increasing time intervals. Results showed significantly different rates of darkening and greening over time between north-facing and south-facing blocks, for both sandstone and limestone. This difference is likely to be representative of the fact that in Northern Ireland’s wet climate and northern-latitude position, the north face of a building will receive less direct sunlight. Therefore north-facing blocks, once wet, will remain damp for much longer than blocks on other façades. This slow-drying phenomenon is much more hospitable for biological colonization and continued growth than the hostile environment of rapid wetting and drying cycles experienced on the south face.

Reproductive biomass in Holcus lanatus clones that differ in their phosphate uptake kinetics and mycorrhizal colonization

In normal populations of the common grass Holcus lanatus there is a polymorphism for arsenate resistance, manifested as suppressed phosphate uptake (SPU), and controlled by a major gene with dominant expression. A natural population of SPU plants had greater arbuscular-mycorrhizal colonization than wild type, nonSPU plants. It was hypothesized that, in order to survive alongside plants with a normal rate of phosphate (P) uptake, SPU plants would be more dependent on mycorrhizal associations. We performed an experiment using plants with SPU phenotypes from both arsenate mine spoils and uncontaminated soils, as well as plants with a nonSPU phenotype. They were grown with and without a mycorrhizal inoculum and added N, which altered plant P requirements. We showed that grasses with SPU phenotypes accumulated more shoot P than nonSPU plants, the opposite of the expected result. SPY plants also produced considerably more flower panicles, and had greater shoot and root biomass. The persistence of SPU phenotypes in normal populations is not necessarily related to mycorrhizal colonization as there were no differences in percentage AM colonization between the phenotypes. Being mycorrhizal reduced flower biomass production, as mycorrhizal SPU plants had lower shoot P concentrations and produced fewer flower panicles than non-mycorrhizal, nonSPU plants. We now hypothesize that the SPU phenotype is brought about by a genotype that results in increased accumulation of P in shoots, and that suppression of the rate of uptake is a consequence of this high shoot P concentration, operating by means of a homeostatic feedback mechanism. We also postulate that increased flower production is linked to a high shoot P concentration. SPU plants thus allocate more resources into seed production, leading to a higher frequency of SPU genes. Increased reproductive allocation reduces vegetative allocation and may affect competitive ability and hence survival, explaining the maintenance of the polymorphism. As mycorrhizal SPU plants behave more like nonSPU plants, AM colonization itself could play a major part in the maintenance of the SPU polymorphism.

The colonization of macroalgal rafts by the genus Idotea (sub-phylum Crustacea; Order Isopoda):An active or passive process?

The association of invertebrate communities with macroalgae rafts has received much attention over recent decades, yet significant gaps in our knowledge remain with respect to the colonization process. Using laboratory-based experiments and in situ field trials in Strangford Lough, Northern Ireland, this study investigated whether members of the known rafting genus Idotea (sub-phylum Crustacea; order Isopoda) could effectively colonize rafts after shore seaweed detachment, or if their presence merely reflected a passive marooning process. Test tank arenas were used to identify traits that may influence the rafting potential of the dominant shore species Idotea granulosa and the well known rafter Idotea baltica. When released mid-water, I. granulosa initially ascended and associated with floating seaweed whereas I. baltica tended to descend with no clear habitat association. These findings conflict with the differential distribution of these Idotea species among rafts and shore algae, thus highlighting the complex nature of the potential of organisms to raft. In the field we considered the relative ability of different Idotea species to colonize tethered rafts composed of Ascophyllum nodosum and Fucus vesiculosus, cleaned of all vagile organisms and deployed at locations adjacent to established intertidal Idotea species populations. At the end of the experiment (after 44 days) rafts were inhabited by known rafting and shoreline species, confirming that colonization can occur after algal detachment. Previously considered shoreline species on occasion outnumbered well known rafters suggesting that a wide range of Idotea species can readily avail of macroalgal rafts as a potential dispersal mechanism or alternative habitat. © 2012 Marine Biological Association of the United Kingdom.

Tea tree oil (5%) body wash versus standard care (Johnson's Baby Softwash) to prevent colonization with methicillin-resistant Staphylococcus aureus in critically ill adults::a randomized controlled trial

OBJECTIVES: To determine whether the daily use of 5% tea tree oil (TTO) body wash (Novabac 5% Skin Wash) compared with standard care [Johnson's Baby Softwash (JBS)] had a lower incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonization.

PATIENTS: The study setting was two intensive care units (ICUs; mixed medical, surgical and trauma) in Northern Ireland between October 2007 and July 2009. The study population comprised 391 patients who were randomized to JBS or TTO body wash.

METHODS: This was a Phase 2/3, prospective, open-label, randomized, controlled trial. Trial registration: ISRCTN65190967. The primary outcome was new MRSA colonization during ICU stay. Secondary outcomes included the incidence of MRSA bacteraemia and maximum increase in sequential organ failure assessment score.

RESULTS: A total of 445 patients were randomized to the study. After randomization, 54 patients were withdrawn; 30 because of a positive MRSA screen at study entry, 11 due to lack of consent, 11 were inappropriately randomized and 2 had adverse reactions. Thirty-nine (10%) patients developed new MRSA colonization (JBS n?=?22, 11.2%; TTO body wash n?=?17, 8.7%). The difference in percentage colonized (2.5%, 95% CI -?8.95 to 3.94; P?=?0.50) was not significant. The mean maximum increase in sequential organ failure assessment score was not significant (JBS 1.44, SD 1.92; TTO body wash 1.28, SD 1.79; P?=?0.85) and no study patients developed MRSA bacteraemia.

CONCLUSIONS: Compared with JBS, TTO body wash cannot be recommended as an effective means of reducing MRSA colonization.

Differences in Mucosal Gene Expression in the Colon of Two Inbred Mouse Strains after Colonization with Commensal Gut Bacteria

The host genotype has been proposed to contribute to individually composed bacterial communities in the gut. To provide deeper insight into interactions between gut bacteria and host, we associated germ-free C3H and C57BL/10 mice with intestinal bacteria from a C57BL/10 donor mouse. Analysis of microbiota similarity between the animals with denaturing gradient gel electrophoresis revealed the development of a mouse strain-specific microbiota. Microarray-based gene expression analysis in the colonic mucosa identified 202 genes whose expression differed significantly by a factor of more than 2. Application of bioinformatics tools demonstrated that functional terms including signaling/secretion, lipid degradation/catabolism, guanine nucleotide/guanylate binding and immune response were significantly enriched in differentially expressed genes. We had a closer look at the 56 genes with expression differences of more than 4 and observed a higher expression in C57BL/10 mice of the genes coding for Tlr1 and Ang4 which are involved in the recognition and response to gut bacteria. A higher expression of Pla2g2a was detected in C3H mice. In addition, a number of interferon-inducible genes were higher expressed in C3H than in C57BL/10 mice including Gbp1, Mal, Oasl2, Ifi202b, Rtp4, Ly6g6c, Ifi27l2a, Usp18, Ifit1, Ifi44, and Ly6g indicating that interferons may play an essential role in microbiota regulation. However, genes coding for interferons, their receptors, factors involved in interferon expression regulation or signaling pathways were not differentially expressed between the two mouse strains. Taken together, our study confirms that the host genotype is involved in the establishment of host-specific bacterial communities in the gut. Based on expression differences after colonization with the same bacterial inoculum, we propose that Pla2g2a and interferon-dependent genes may contribute to this phenomenon.

New insights on postglacial colonization in western Europe: the phylogeography of the Leisler’s bat (Nyctalus leisleri)

Despite recent advances in the understanding of the interplay between a dynamic physical environment and phylogeography in Europe, the origins of contemporary Irish biota remain uncertain. Current thinking is that Ireland was colonized post-glacially from southern European refugia, following the end of the last glacial maximum(LGM), some 20 000 years BP. The Leisler’s bat (Nyctalus leisleri), one of the few native Irish mammal species, is widely distributed throughout Europe but, with the exception of Ireland, is generally rare and considered vulnerable. We investigate the origins and phylogeographic relationships of Irish populations in relation to those across Europe, including the closely related species N. azoreum. We use a combination of approaches, including mitochondrial and nuclear DNA markers, in addition to approximate Bayesian computation and palaeo-climatic species distribution modelling. Molecular analyses revealed two distinct and diverse European mitochondrialDNAlineages,which probably diverged in separate glacial refugia. Awestern lineage, restricted to Ireland, Britain and the Azores, comprises Irish and British N. leisleri and N. azoreum specimens; an eastern lineage is distributed throughout mainland Europe. Palaeo-climatic projections indicate suitable habitats during the LGM, including known glacial refugia, in addition to potential novel cryptic refugia along the western fringe of Europe. These results may be applicable to populations of many species.

Effects of orally administered Bdellovibrio bacteriovorus on the well-being and Salmonella colonization of young chicks

Bdellovibrio bacteriovorus is a bacterium which preys upon and kills Gram-negative bacteria, including the zoonotic pathogens Escherichia coli and Salmonella. Bdellovibrio has potential as a biocontrol agent, but no reports of it being tested in living animals have been published, and no data on whether Bdellovibrio might spread between animals are available. In this study, we tried to fill this knowledge gap, using B. bacteriovorus HD100 doses in poultry with a normal gut microbiota or predosed with a colonizing Salmonella strain. In both cases, Bdellovibrio was dosed orally along with antacids. After dosing non-Salmonella-infected birds with Bdellovibrio, we measured the health and well-being of the birds and any changes in their gut pathology and culturable microbiota, finding that although a Bdellovibrio dose at 2 days of age altered the overall diversity of the natural gut microbiota in 28-day-old birds, there were no adverse effects on their growth and well-being. Drinking water and fecal matter from the pens in which the birds were housed as groups showed no contamination by Bdellovibrio after dosing. Predatory Bdellovibrio orally administered to birds that had been predosed with a gut-colonizing Salmonella enterica serovar Enteritidis phage type 4 strain (an important zoonotic pathogen) significantly reduced Salmonella numbers in bird gut cecal contents and reduced abnormal cecal morphology, indicating reduced cecal inflammation, compared to the ceca of the untreated controls or a nonpredatory ΔpilA strain, suggesting that these effects were due to predatory action. This work is a first step to applying Bdellovibrio therapeutically for other animal, and possibly human, infections.

Tumorigenesis and peritoneal colonization from fallopian tube epithelium

Ovarian cancer is the most lethal gynecological malignancy, primarily because its origin and initiation factors are unknown. A secretory murine oviductal epithelial (MOE) model was generated to address the hypothesis that the fallopian tube is an origin for high-grade serous cancer. MOE cells were stably altered to express mutation in p53, silence PTEN, activate AKT, and amplify KRAS alone and in combination, to define if this cell type gives rise to tumors and what genetic alterations are required to drive malignancy. Cell lines were characterized in vitro and allografted into mice. Silencing PTEN formed high-grade carcinoma with wide spread tumor explants including metastasis into the ovary. Addition of p53 mutation to PTEN silencing did not enhance this phenotype, whereas addition of KRAS mutation reduced survival. Interestingly, PTEN silencing and KRAS mutation originating from ovarian surface epithelium generated endometrioid carcinoma, suggesting that different cellular origins with identical genetic manipulations can give rise to distinct cancer histotypes. Defining the roles of specific signaling modifications in tumorigenesis from the fallopian tube/oviduct is essential for early detection and development of targeted therapeutics. Further, syngeneic MOE allografts provide an ideal model for pre-clinical testing in an in vivo environment with an intact immune system.