Treatment with high-dose antidepressants severely exacerbates the pathological outcome of experimental <i>Escherichia coli</i> infections in poultry

There is an urgent need for novel antibiotics as the current antibiotics are losing their value due to increased resistance among clinically important bacteria. Sertraline, an on-marked anti-depressive drug, has been shown to modify bacterial activity in vitro, including increasing the susceptibility of Escherichia coli to antibiotics. The aim of the present study was to investigate if the antimicrobial activity of sertraline could be documented under clinical settings, hereunder if sertraline could potentiate the effect of tetracycline in treatment of an experimentally induced ascending infection in poultry. A total of 40 chickens were divided in four groups of 10 chickens each. All chickens were challenged with 4x103 colony forming units (CFU) of a tetracycline resistant E. coli strain using a surgical infection model, and subsequently treated with either high-dose sertraline, tetracycline, a combination hereof or received no treatment. Seven days post challenge all birds were submitted to necropsy and scored pathologically for lesions. The average lesion scores were significantly higher (P<0.05) in the groups that were treated with high-dose sertraline or high-dose sertraline combined with tetracycline. In conclusion high-dose treatments (four times the maximum therapeutic dose for treating human depression) with sertraline as an adjuvant for treatment of antibiotic resistant E. coli infections exacerbate the pathological outcome of infection in chickens

Physicochemical factors influence the abundance and culturability of human enteric pathogens and fecal indicator organisms in estuarine water and sediment

To assess fecal pollution in coastal waters, current monitoring is reliant on culture-based enumeration of bacterial indicators, which does not account for the presence of viable but non-culturable or sediment-associated micro-organisms, preventing effective quantitative microbial risk assessment (QMRA). Seasonal variability in viable but non-culturable or sediment-associated bacteria challenge the use of fecal indicator organisms (FIOs) for water monitoring. We evaluated seasonal changes in FIOs and human enteric pathogen abundance in water and sediments from the Ribble and Conwy estuaries in the UK. Sediments possessed greater bacterial abundance than the overlying water column, however, key pathogenic species (Shigella spp., Campylobacter jejuni, Salmonella spp., hepatitis A virus, hepatitis E virus and norovirus GI and GII) were not detected in sediments. Salmonella was detected in low levels in the Conwy water in spring/summer and norovirus GII was detected in the Ribble water in winter. The abundance of E. coli and Enterococcus spp. quantified by culture-based methods, rarely matched the abundance of these species when measured by qPCR. The discrepancy between these methods was greatest in winter at both estuaries, due to low CFU's, coupled with higher gene copies (GC). Temperature accounted for 60% the variability in bacterial abundance in water in autumn, whilst in winter salinity explained 15% of the variance. Relationships between bacterial indicators/pathogens and physicochemical variables were inconsistent in sediments, no single indicator adequately described occurrence of all bacterial indicators/pathogens. However, important variables included grain size, porosity, clay content and concentrations of Zn, K, and Al. Sediments with greater organic matter content and lower porosity harbored a greater proportion of non-culturable bacteria (including dead cells and extracellular DNA) in winter. Here, we show the link between physicochemical variables and season which govern culturability of human enteric pathogens and FIOs. Therefore, knowledge of these factors is critical for accurate microbial risk assessment. Future water quality management strategies could be improved through monitoring sediment-associated bacteria and non-culturable bacteria. This could facilitate source apportionment of human enteric pathogens and FIOs and direct remedial action to improve water quality

Development of a Chemical Source Apportionment Decision Support Framework for Catchment Management

EU legislation, including the Water Framework Directive, has led to the application of increasingly stringent quality standards for a wide range of chemical contaminants in surface waters. This has raised the question of how to determine and to quantify the sources of such substances so that measures can be taken to address breaches of these quality standards using the polluter pays principle. Contaminants enter surface waters via a number of diffuse and point sources. Decision support tools are required to assess the relative magnitudes of these sources and to estimate the impacts of any programmes of measures. This work describes the development and testing of a modeling framework, the Source Apportionment Geographical Information System (SAGIS). The model uses readily available national data sets to estimate contributions of a number of nutrients (nitrogen and phosphorus), metals (copper, zinc, cadmium, lead, mercury, and nickel) and organic chemicals (a phthalate and a number of polynuclear aromatic hydrocarbons) from multiple sector sources. Such a tool has not previously been available on a national scale for such a wide range of chemicals. It is intended to provide a common platform to assist stakeholders in future catchment management

Minimal inhibitory concentration (MIC) of sertraline and tetracycline alone or combined.

<p>For each combination exposure on sertraline and tetracycline, the fractional inhibitory concentration index (FICI) is stated.</p

Treatment with high-dose antidepressants severely exacerbates the pathological outcome of experimental <i>Escherichia coli</i> infections in poultry

<div><p>There is an urgent need for novel antibiotics as the current antibiotics are losing their value due to increased resistance among clinically important bacteria. Sertraline, an on-marked anti-depressive drug, has been shown to modify bacterial activity <i>in vitro</i>, including increasing the susceptibility of <i>Escherichia coli</i> to antibiotics. The aim of the present study was to investigate if the antimicrobial activity of sertraline could be documented under clinical settings, hereunder if sertraline could potentiate the effect of tetracycline in treatment of an experimentally induced ascending infection in poultry. A total of 40 chickens were divided in four groups of 10 chickens each. All chickens were challenged with 4x10³ colony forming units (CFU) of a tetracycline resistant <i>E</i>. <i>coli</i> strain using a surgical infection model, and subsequently treated with either high-dose sertraline, tetracycline, a combination hereof or received no treatment. Seven days post challenge all birds were submitted to necropsy and scored pathologically for lesions. The average lesion scores were significantly higher (P<0.05) in the groups that were treated with high-dose sertraline or high-dose sertraline combined with tetracycline. In conclusion high-dose treatments (four times the maximum therapeutic dose for treating human depression) with sertraline as an adjuvant for treatment of antibiotic resistant <i>E</i>. <i>coli</i> infections exacerbate the pathological outcome of infection in chickens.</p></div

Overview of experimental groups.

<p>Each group consisted of 10 commercially brown layers, 45 weeks of age.</p

Colony-forming units (CFU).

<p>CFU per gram salpinx in the different treatment groups. Vertical bars indicate the standard deviation.</p

Weight changes during infection.

<p>Percent weight change seven days after infection compared to before infection per chicken in the different treatment groups.</p