Empiric antibiotic therapy in urinary tract infection in patients with risk factors for antibiotic resistance in a German emergency department

Background: The aim of this study was to identify clinical risk factors for antimicrobial resistances and multidrug resistance (MDR) in urinary tract infections (UTI) in an emergency department in order to improve empirical therapy. Methods: UTI cases from an emergency department (ED) during January 2013 and June 2015 were analyzed. Differences between patients with and without resistances towards Ciprofloxacin, Piperacillin with Tazobactam (Pip/taz), Gentamicin, Cefuroxime, Cefpodoxime and Ceftazidime were analyzed with Fisher’s exact tests. Results were used to identify risk factors with logistic regression modelling. Susceptibility rates were analyzed in relation to risk factors. Results: One hundred thirty-seven of four hundred sixty-nine patients who met the criteria of UTI had a positive urine culture. An MDR pathogen was found in 36.5% of these. Overall susceptibility was less than 85% for standard antimicrobial agents. Logistic regression identified residence in nursing homes, male gender, hospitalization within the last 30 days, renal transplantation, antibiotic treatment within the last 30 days, indwelling urinary catheter and recurrent UTI as risk factors for MDR or any of these resistances. For patients with no risk factors Ciprofloxacin had 90%, Pip/taz 88%, Gentamicin 95%, Cefuroxime 98%, Cefpodoxime 98% and Ceftazidime 100% susceptibility. For patients with 1 risk factor Ciprofloxacin had 80%, Pip/taz 80%, Gentamicin 88%, Cefuroxime 78%, Cefpodoxime 78% and Ceftazidime 83% susceptibility. For 2 or more risk factors Ciprofloxacin drops its susceptibility to 52%, Cefuroxime to 54% and Cefpodoxime to 61%. Pip/taz, Gentamicin and Ceftazidime remain at 75% and 77%, respectively. Conclusions: We identified several risk factors for resistances and MDR in UTI. Susceptibility towards antimicrobials depends on these risk factors. With no risk factor cephalosporins seem to be the best choice for empiric therapy, but in patients with risk factors the beta-lactam penicillin Piperacillin with Tazobactam is an equal or better choice compared to fluoroquinolones, cephalosporins or gentamicin. This study highlights the importance of monitoring local resistance rates and its risk factors in order to improve empiric therapy in a local environment

Extension of the Chiral Perturbation Theory Meson Lagrangian to Order P6P^6

We have derived the most general chirally invariant Lagrangian ${\cal L}_6$ for the meson sector at order $p^6$. The result provides an extension of the standard Gasser-Leutwyler Lagrangian ${\cal L}_4$ to one higher order, including as well all the odd intrinsic parity terms in the Lagrangian. The most difficult part of the derivation was developing a systematic strategy so as to get all of the independent terms and eliminate the redundant ones in an efficient way. The 'equation of motion' terms, which are redundant in the sense that they can be transformed away via field transformations, are separated out explicitly. The resulting Lagrangian has been separated into groupings of terms contributing to increasingly more complicated processes, so that one does not have to deal with the full result when calculating $p^6$ contributions to simple processes.Comment: 59 pages in LaTex, using RevTex macro, TRIUMF preprint TRI-PP-94-6

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

Trouble with zombies: Bare life, Muselmanner and displaced people

This article considers the increase in media representations of zombies during the first decade of the 2000s. It argues that a connection can be read between the new preoccupation with zombies and anxieties over the apparent threat posed by those without rights attempting to enter Western countries. The article sets up a theoretical argument using the work of Giorgio Agamben. Taking on board Agamben's discussion of ‘bare life’, the article follows Agamben in making a link between this idea and the Muselmann, the Jew reduced to the walking dead in the concentration and death camps. For Agamben, bare life is central to the functioning of the modern state. The article suggests that bare life is a way of connecting the Muselmann with the zombie as that monster has been elaborated in films since George Romero's Night of the Living Dead (1968). Indeed, where Agamben argues that the werewolf was the characterising monster of the premodern era, this article argues that the zombie is the characterising monster of the modern era. The article goes on to make the connection between bare life, Muselmänner, zombies and displaced people, most commonly understood as asylum seekers

Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane

Vesicle fusion is executed via formation of an Ω-shaped structure (Ω-profile), followed by closure (kiss-and-run) or merging of the Ω-profile into the plasma membrane (full fusion). Although Ω-profile closure limits release but recycles vesicles economically, Ω-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Ω-profile merging is mediated is poorly understood in endocrine cells and neurons containing small ∼30–300 nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates Ω-profile merging by providing sufficient plasma membrane tension to shrink the Ω-profile in neuroendocrine chromaffin cells containing ∼300 nm vesicles. Actin-directed compounds also induce Ω-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Ω-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Ω-profile merging

Founder effects drive the genetic structure of passively dispersed aquatic invertebrates

Populations of passively dispersed organisms in continental aquatic habitats typically show high levels of neutral genetic differentiation despite their high dispersal capabilities. Several evolutionary factors, including founder events, local adaptation, and life cycle features such as high population growth rates and the presence of propagule banks, have been proposed to be responsible for this paradox. Here, we have modeled the colonization process to assess the impact of migration rate, population growth rate, population size, local adaptation and life-cycle features on the population genetic structure in these organisms. Our simulations show that the strongest effect on population structure are persistent founder effects, resulting from the interaction of a few population founders, high population growth rates, large population sizes and the presence of diapausing egg banks. In contrast, the role of local adaptation, genetic hitchhiking and migration is limited to small populations in these organisms. Our results indicate that local adaptation could have different impact on genetic structure in different groups of zooplankters