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Nieder-Ingelheim, Germany

Harris L.G.,University of Swansea | Murray S.,University of Swansea | Pascoe B.,University of Swansea | Bray J.,University of Oxford | And 19 more authors.
PLoS ONE | Year: 2016

Bacterial species comprise related genotypes that can display divergent phenotypes with important clinical implications. Staphylococcus epidermidis is a common cause of nosocomial infections and, critical to its pathogenesis, is its ability to adhere and form biofilms on surfaces, thereby moderating the effect of the host's immune response and antibiotics. Commensal S. epidermidis populations are thought to differ from those associated with disease in factors involved in adhesion and biofilm accumulation. We quantified the differences in biofilm formation in 98 S. epidermidis isolates from various sources, and investigated population structure based on ribosomal multilocus typing (rMLST) and the presence/absence of genes involved in adhesion and biofilm formation. All isolates were able to adhere and form biofilms in in vitro growth assays and confocal microscopy allowed classification into 5 biofilm morphotypes based on their thickness, biovolume and roughness. Phylogenetic reconstruction grouped isolates into three separate clades, with the isolates in the main disease associated clade displaying diversity in morphotype. Of the biofilm morphology characteristics, only biofilm thickness had a significant association with clade distribution. The distribution of some known adhesion-associated genes (aap and sesE) among isolates showed a significant association with the species clonal frame. These data challenge the assumption that biofilm-associated genes, such as those on the ica operon, are genetic markers for less invasive S. epidermidis isolates, and suggest that phenotypic characteristics, such as adhesion and biofilm formation, are not fixed by clonal descent but are influenced by the presence of various genes that are mobile among lineages. © 2016 Harris et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Heudorf U.,MRE Netz Rhein Main | Farber D.,MRE Netz Rhein Main | Mischler D.,MRE Netz Rhein Main | Schade M.,MRE Netz Rhein Main | And 4 more authors.
Rehabilitation (Germany) | Year: 2015

Background: While a limited number of studies have investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in medical rehabilitation institutions, almost no data on the colonization of rehabilitation patients with multiresistant gram-negative rods is available. Here we report on a large multicenter study on the prevalence of MRSA and multiresistant pathogens in rehabilitation institutions in the Rhine-Main area in 2014. Materials and Methods: Altogether, 21 rehabilitation hospitals participated. For all patients, age, gender, previous history of hospitalizations, surgery, previous colonization with multidrug-resistant organisms, use of a medical device, current antimicrobial therapy, and the current infection status were ascertained. On voluntary basis, nare and throat swabs were taken for analysis of MRSA and rectal swabs were tested for extended spectrum betalactamase-producing gram-negative bacteria (ESBL). Results: 50% of 2 440 patients had a history of hospitalization within the previous 6 months while 39% had undergone surgery during the past 30 days. Approximately a quarter of the patients had been transferred to a rehabilitation hospital directly from an acute care hospital, had been under antimicrobial therapy with the past three months, or had travelled to a foreign country within the previous year. Risk factors such as lesions of the intact skin or presence of medical devices were rarely reported (< 5%) within the exception of patients undergoing geriatric or neurologic acute care rehabilitation. 0.7% (15/2155) of the patients were colonized with MRSA, while 7.7% (110/1434) showed a positive result for ESBL. The highest prevalence rates for multiresistant organisms were encountered among patients with neurologic rehabilitation (MRSA, 1.3%, and ESBL, 10.2%) or with geriatric rehabilitation (MRSA, 9.4%, and ESBL, 22.7%). Conclusion: In the rehabilitation patient population, the prevalence rates of MRSA and ESBL were found to be in the range of rates encountered in the general population (reported rates for MRSA, 0.5%, and ESBL, 6.3%). The known risk factors for MRSA such as skin lesions, medical devices and previous history for MRSA were also confirmed among this patient population. Direct transfer from an acute care hospital, antimicrobial treatment during the past 3 months, and wounds proved significant risk factors for ESBL colonization. Patients of neurologic rehabilitation and geriatric patients showed the highest rates of risk factors and the highest prevalence rates of multidrug-resistant organisms. It appears to be of importance for rehabilitation hospitals to be geared to the needs of patients with multidrug-resistant organisms, and prevent the transmission of these pathogens by appropriate hygiene measures. © Georg Thieme Verlag KG Stuttgart, New York.

Meric G.,University of Swansea | Miragaia M.,New University of Lisbon | De Been M.,University Utrecht | Yahara K.,University of Swansea | And 20 more authors.
Genome Biology and Evolution | Year: 2015

The opportunistic pathogens Staphylococcus aureus and Staphylococcus epidermidis represent major causes of severe nosocomial infection, and are associated with high levels of mortality and morbidity worldwide. These species are both common commensals on the human skin and in the nasal pharynx, but are genetically distinct, differing at 24% average nucleotide divergence in 1,478 core genes. To better understand the genome dynamics of these ecologically similar staphylococcal species, we carried out a comparative analysis of 324 S. aureus and S. epidermidis genomes, including 83 novel S. epidermidis sequences. A reference pan-genome approach and whole genome multilocus-sequence typing revealed that around half of the genome was shared between the species. Based on a BratNextGen analysis, homologous recombination was found to have impacted on 40% of the core genes in S. epidermidis, but on only 24% of the core genes in S. aureus. Homologous recombination between the species is rare, with a maximum of nine gene alleles shared between any two S. epidermidis and S. aureus isolates. In contrast, there was considerable interspecies admixture of mobile elements, in particular genes associated with the SaPIn1 pathogenicity island, metal detoxification, and the methicillin-resistance island SCCmec. Our data and analysis provide a context for considering the nature of recombinational boundaries between S. aureus and S. epidermidis and, the selective forces that influence realized recombination between these species. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Allen S.J.,University of Swansea | Wareham K.,Clinical Research Unit | Wang D.,London School of Hygiene and Tropical Medicine | Bradley C.,County Durham and Darlington Foundation Trust | And 10 more authors.
Health Technology Assessment | Year: 2013

Background: Antibiotic-associated diarrhoea (AAD) occurs most commonly in older people admitted to hospital and within 12 weeks of exposure to broad-spectrum antibiotics. Although usually a mild and self-limiting illness, the 15-39% of cases caused by Clostridium difficile infection [C. difficile diarrhoea (CDD)] may result in severe diarrhoea and death. Previous research has shown that probiotics, live microbial organisms that, when administered in adequate numbers, are beneficial to health, may be effective in preventing AAD and CDD. Objectives: To determine the clinical effectiveness and cost-effectiveness of a high-dose, multistrain probiotic in the prevention of AAD and CDD in older people admitted to hospital. Design: A multicentre, randomised, double-blind, placebo-controlled, parallel-arm trial. Setting: Medical, surgical and elderly care inpatient wards in five NHS hospitals in the UK. Participants: Eligible patients were aged ≥ 65 years, were exposed to one or more oral or parenteral antibiotics and were without pre-existing diarrhoeal disorders, recent CDD or at risk of probiotic adverse effects. Out of 17,420 patients screened, 2981 (17.1%) were recruited. Participants were allocated sequentially according to a computer-generated random allocation sequence; 1493 (50.1%) were allocated to the probiotic and 1488 (49.9%) to the placebo arm. Interventions: Vegetarian capsules containing two strains of lactobacilli and two strains of bifidobacteria (a total of 6 × 1010 organisms per day) were taken daily for 21 days. The placebo was inert maltodextrin powder in identical capsules. Main outcome measures: The occurrence of AAD within 8 weeks and CDD within 12 weeks of recruitment was determined by participant follow-up and checking hospital laboratory records by research nurses who were blind to arm allocation. Results: Analysis based on the treatment allocated included 2941 (98.7%) participants. Potential risk factors for AAD at baseline were similar in the two study arms. Frequency of AAD (including CDD) was similar in the probiotic (159/1470, 10.8%) and placebo arms [153/1471, 10.4%; relative risk (RR) 1.04; 95% confidence interval (CI) 0.84 to 1.28; p = 0.71]. CDD was an uncommon cause of AAD and occurred in 12/1470 (0.8%) participants in the probiotic and 17/1471 (1.2%) in the placebo arm (RR 0.71; 95% CI 0.34 to 1.47; p = 0.35). Duration and severity of diarrhoea, common gastrointestinal symptoms, serious adverse events and quality of life measures were also similar in the two arms. Total health-care costs per patient did not differ significantly between the probiotic (£8020; 95% CI £7620 to £8420) and placebo (£8010; 95% CI £7600 to £8420) arms. Conclusion: We found no evidence that probiotic administration was effective in preventing AAD. Although there was a trend towards reduced CDD in the probiotic arm, on balance, the administration of this probiotic seems unlikely to benefit older patients exposed to antibiotics. A better understanding of the pathogenesis of AAD and CDD and the strain-specific effects of probiotics is needed before further clinical trials of specific microbial preparations are undertaken. Evaluation of the effectiveness of other probiotics will be difficult where other measures, such as antibiotic stewardship, have reduced CDD rates. © Queen's Printer and Controller of HMSO 2013.

Harris L.G.,University of Swansea | Nigam Y.,University of Swansea | Sawyer J.,University of Swansea | Mack D.,University of Swansea | And 2 more authors.
Applied and Environmental Microbiology | Year: 2013

Staphylococcus aureus and Staphylococcus epidermidis biofilms cause chronic infections due to their ability to form biofilms. The excretions/secretions of Lucilia sericata larvae (maggots) have effective activity for debridement and disruption of bacterial biofilms. In this paper, we demonstrate how chymotrypsin derived from maggot excretions/secretions disrupts protein-dependent bacterial biofilm formation mechanisms. © 2013, American Society for Microbiology.

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