Temporal trends of extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates in in- and outpatients in Switzerland, 2004 to 2011

Increasing trends for invasive infections with extended-spectrum cephalosporin-resistant (ESC-R) Enterobacteriaceae have been described in many countries worldwide. However, data on the rates of ESC-R isolates in non-invasive infections and in the outpatient setting are scarce. We used a laboratory-based nationwide surveillance system to compare temporal trends of ESC-R rates in Escherichia coli and Klebsiella pneumoniae for in- and outpatients in Switzerland. Our data showed a significant increase in ESC-R rates from 1% to 5.8% in E. coli (p<0.001) and from 1.1% to 4.4% in K. pneumoniae (p=0.002) during an eight-year period (2004–2011). For E. coli, the increase was significantly higher in inpatients (from 1.2% to 6.6%), in patients residing in eastern Switzerland (from 1.0% to 6.2%), in patients older than 45 years (from 1.2% to 6.7%), and in male patients (from 1.2% to 8.1%). While the increase in inpatients was linear (p<0.001) for E. coli, the increase of ESC R K. pneumoniae isolates was the result of multiple outbreaks in several institutions. Notably, an increasing proportion of ESC-R E. coli was co-resistant to both trimethoprim-sulfamethoxazole and quinolones (42% in 2004 to 49.1% in 2011, p=0.009), further limiting the available oral therapeutic options.

Drug-related emergency department visits by elderly patients presenting with non-specific complaints

BACKGROUND Since drug-related emergency department (ED) visits are common among older adults, the objectives of our study were to identify the frequency of drug-related problems (DRPs) among patients presenting to the ED with non-specific complaints (NSC), such as generalized weakness and to evaluate responsible drug classes. METHODS Delayed type cross-sectional diagnostic study with a prospective 30 day follow-up in the ED of the University Hospital Basel, Switzerland. From May 2007 until April 2009, all non-trauma patients presenting to the ED with an Emergency Severity Index (ESI) of 2 or 3 were screened and included, if they presented with non-specific complaints. After having obtained complete 30-day follow-up, two outcome assessors reviewed all available information, judged whether the initial presentation was a DRP and compared their judgment with the initial ED diagnosis. Acute morbidity ("serious condition") was allocated to individual cases according to predefined criteria. RESULTS The study population consisted of 633 patients with NSC. Median age was 81 years (IQR 72/87), and the mean Charlson comorbidity index was 2.5 (IQR 1/4). DRPs were identified in 77 of the 633 cases (12.2%). At the initial assessment, only 40% of the DRPs were correctly identified. 64 of the 77 identified DRPs (83%) fulfilled the criteria "serious condition". Polypharmacy and certain drug classes (thiazides, antidepressants, benzodiazepines, anticonvulsants) were associated with DRPs. CONCLUSION Elderly patients with non-specific complaints need to be screened systematically for drug-related problems. TRIAL REGISTRATION ClinicalTrials.gov: NCT00920491.

Vesicular stomatitis virus replicon expressing the VP2 outer capsid protein of bluetongue virus serotype 8 induces complete protection of sheep against challenge infection.

Bluetongue virus (BTV) is an arthropod-borne pathogen that causes an often fatal, hemorrhagic disease in ruminants. Different BTV serotypes occur throughout many temperate and tropical regions of the world. In 2006, BTV serotype 8 (BTV-8) emerged in Central and Northern Europe for the first time. Although this outbreak was eventually controlled using inactivated virus vaccines, the epidemic caused significant economic losses not only from the disease in livestock but also from trade restrictions. To date, BTV vaccines that allow simple serological discrimination of infected and vaccinated animals (DIVA) have not been approved for use in livestock. In this study, we generated recombinant RNA replicon particles based on single-cycle vesicular stomatitis virus (VSV) vectors. Immunization of sheep with infectious VSV replicon particles expressing the outer capsid VP2 protein of BTV-8 resulted in induction of BTV-8 serotype-specific neutralizing antibodies. After challenge with a virulent BTV-8 strain, the vaccinated animals neither developed signs of disease nor showed viremia. In contrast, immunization of sheep with recombinant VP5 - the second outer capsid protein of BTV - did not confer protection. Discrimination of infected from vaccinated animals was readily achieved using an ELISA for detection of antibodies against the VP7 antigen. These data indicate that VSV replicon particles potentially represent a safe and efficacious vaccine platform with which to control future outbreaks by BTV-8 or other serotypes, especially in previously non-endemic regions where discrimination between vaccinated and infected animals is crucial.

The Complexity of Non-Iterated Probabilistic Justification Logic

The logic PJ is a probabilistic logic defined by adding (noniterated) probability operators to the basic justification logic J. In this paper we establish upper and lower bounds for the complexity of the derivability problem in the logic PJ. The main result of the paper is that the complexity of the derivability problem in PJ remains the same as the complexity of the derivability problem in the underlying logic J, which is π[p/2] -complete. This implies that the probability operators do not increase the complexity of the logic, although they arguably enrich the expressiveness of the language.

Complete protection against P. berghei malaria upon heterologous prime/boost immunization against circumsporozoite protein employing Salmonella type III secretion system and Bordetella adenylate cyclase toxoid

Sterile immunity against malaria can be achieved by the induction of IFNgamma-producing CD8(+) T cells that target infected hepatocytes presenting epitopes of the circumsporozoite protein (CSP). In the present study we evaluate the protective efficacy of a heterologous prime/boost immunization protocol based on the delivery of the CD8(+) epitope of Plasmodium berghei CSP into the MHC class I presentation pathway, by either a type III secretion system of live recombinant Salmonella and/or by direct translocation of a recombinant Bordetella adenylate cyclase toxoid fusion (ACT-CSP) into the cytosol of professional antigen-presenting cells (APCs). A single intraperitoneal application of the recombinant ACT-CSP toxoid, as well as a single oral immunization with the Salmonella vaccine, induced a specific CD8(+) T cell response, which however conferred only a partial protection on mice against a subsequent sporozoite challenge. In contrast, a heterologous prime/boost vaccination with the live Salmonella followed by ACT-CSP led to a significant enhancement of the CSP-specific T cell response and induced complete protection in all vaccinated mice.