Emergence of extensively drug-resistant Haemophilus parainfluenzae in Switzerland

Two homosexual men were colonized in the urethra with Haemophilus parainfluenzae nonsusceptible to ampicillin (MIC, 8 μg/ml), amoxicillin-clavulanate (MIC, 4 μg/ml), cefotaxime (MIC, 1.5 μg/ml), cefepime (MIC, 3 μg/ml), meropenem (MIC, 0.5 μg/ml), cefuroxime, azithromycin, ciprofloxacin, tetracycline, and chloramphenicol (all MICs, ≥ 32 μg/ml). Repetitive extragenic palindromic PCR (rep-PCR) showed that the strains were indistinguishable. The isolates had amino acid substitutions in PBP3, L4, GyrA, and ParC and possessed Mef(A), Tet(M), and CatS resistance mechanisms. This is the first report of extensively drug-resistant (XDR) H. parainfluenzae.

Non-phenotypic tests to detect and characterize antibiotic resistance mechanisms in Enterobacteriaceae

In the past 2 decades, we have observed a rapid increase of infections due to multidrug-resistant Enterobacteriaceae. Regrettably, these isolates possess genes encoding for extended-spectrum β-lactamases (e.g., blaCTX-M, blaTEM, blaSHV) or plasmid-mediated AmpCs (e.g., blaCMY) that confer resistance to last-generation cephalosporins. Furthermore, other resistance traits against quinolones (e.g., mutations in gyrA and parC, qnr elements) and aminoglycosides (e.g., aminoglycosides modifying enzymes and 16S rRNA methylases) are also frequently co-associated. Even more concerning is the rapid increase of Enterobacteriaceae carrying genes conferring resistance to carbapenems (e.g., blaKPC, blaNDM). Therefore, the spread of these pathogens puts in peril our antibiotic options. Unfortunately, standard microbiological procedures require several days to isolate the responsible pathogen and to provide correct antimicrobial susceptibility test results. This delay impacts the rapid implementation of adequate antimicrobial treatment and infection control countermeasures. Thus, there is emerging interest in the early and more sensitive detection of resistance mechanisms. Modern non-phenotypic tests are promising in this respect, and hence, can influence both clinical outcome and healthcare costs. In this review, we present a summary of the most advanced methods (e.g., next-generation DNA sequencing, multiplex PCRs, real-time PCRs, microarrays, MALDI-TOF MS, and PCR/ESI MS) presently available for the rapid detection of antibiotic resistance genes in Enterobacteriaceae. Taking into account speed, manageability, accuracy, versatility, and costs, the possible settings of application (research, clinic, and epidemiology) of these methods and their superiority against standard phenotypic methods are discussed.

Characterization of Neisseria gonorrhoeae isolates detected in Switzerland (1998–2012): emergence of multidrug-resistant clones less susceptible to cephalosporins

Background: The spread of Neisseria gonorrhoeae (Ng) isolates resistant to the clinically implemented antibiotics is challenging the efficacy of treatments. Unfortunately, phenotypic and molecular data regarding Ng detected in Switzerland are scarce. Methods: We compared the characteristics of Ng detected during 1998–2001 (n = 26) to those detected during 2009–2012 (n = 34). MICs were obtained with the Etest and interpreted as non-susceptible (non-S) according to EUCAST criteria. Sequence type (ST) was achieved implementing the NG-MAST. BlaTEM, ponA, penA, mtrR, penB, tet (M), gyrA, parC, mefA, ermA/B/C/F, rplD, rplV, and 23S rRNA genes were analyzed. Results: The following susceptibility results were obtained (period: % of non-S, MIC90 in mg/L): penicillin (1998–2001: 42.3%, 3; 2009–2012: 85.3%, 16), cefixime (1998–2001: 0%, ≤0.016; 2009–2012: 8.8%, 0.125), ceftriaxone (1998–2001: 0%, 0.004; 2009–2012: 0%, 0.047), ciprofloxacin (1998–2001: 7.7%, 0.006; 2009–2012: 73.5%, ≥32), azithromycin (1998–2001: 11.5%, 0.25; 2009–2012: 23.6%, 0.38), tetracycline (1998–2001: 65.4%, 12; 2009–2012: 88.2%, 24), spectinomycin (1998–2001: 0%, 12; 2009–2012: 0%, 8). The prevalence of multidrug-resistant (MDR) isolates increased from 7.7% in 1998–2001 to 70.6% in 2009–2012. International STs and genogroups (G) emerged during 2009–2012 (G1407, 29.4%; G2992, 11.7%; G225, 8.8%). These isolates possessed distinctive mechanisms of resistance (e.g., G1407: PBP1 with L421, PBP2 pattern XXXIV, GyrA with S91F and D95G, ParC with S87R, PorB with G120K and A121N, mtrR promoter with A deletion). Conclusions: The prevalence of penicillin- ciprofloxacin- and tetracycline-resistant Ng has reached dramatic levels, whereas cefixime and ceftriaxone show MICs that tend to increase during time. International MDR clones less susceptible to cephalosporins are rapidly emerging indicating that the era of untreatable gonococcal infections is close.

Le vicus de Bliesbruck et la villa de Reinheim. Une association inégale

Le Parc archéologique européen de Bliesbruck-Reinheim fait partie des sites archéologiques les plus visités des provinces du nord-ouest de l’Empire romain. On se trouve là non seulement dans un lieu de promenade agréable occupé très tôt par les hommes, mais on flâne aussi à travers un vicus, une petite ville romaine, on entre dans ses maisons pour y regarder leur aménagement, on s’attarde dans des thermes publics bien conservés et on se sent plongé dans l’histoire des premiers siècles de notre ère.

OXA-48 carbapenemase-producing Salmonella enterica serovar Kentucky isolate of sequence type 198 in a patient transferred from Libya to Switzerland

Here, we report a case of OXA-48-producing Salmonella enterica serovar Kentucky of sequence type 198 (ST198) from perianal screening cultures of a patient transferred from Libya to Switzerland. The blaOXA-48 gene was carried by Tn1999.2 and located on an ∼60-kb IncL/M plasmid. This Salmonella strain also possessed the blaVEB-8, aac(6)-Ib, tet(A), sul1, and mphA resistance genes and substitutions in GyrA (Ser83Phe and Asp87Asn) and ParC (Ser80Ile). This finding emphasizes that prompt screening strategies are essential to prevent the dissemination of carbapenemase producers imported from countries where they are endemic.

Emergence of Klebsiella pneumoniae co-producing NDM-1, OXA-48, CTX-M-15, CMY-16, QnrA and ArmA in Switzerland

Extensively drug-resistant (XDR) Klebsiella pneumoniae isolates usually carry a single carbapenemase (e.g. KPC, NDM, OXA-48-like). Here we describe an XDR K. pneumoniae of sequence type 101 that was detected in the screening rectal swab of a patient transferred from the intensive care unit of a hospital located in Belgrade (Serbia) to Bern University Hospital (Switzerland). The isolate was resistant to all antibiotics with the exception of colistin [minimum inhibitory concentration] (MIC≤0.125μg/mL), tigecycline (MIC=0.5μg/mL) and fosfomycin (MIC=2μg/mL). The isolate co-possessed class B (NDM-1) and class D (OXA-48) carbapenemases, class A extended-spectrum β-lactamase (CTX-M-15), class C cephalosporinase (CMY-16), ArmA 16S rRNA methyltransferase, substitutions in GyrA and ParC, loss of OmpK35 porin, as well as other genes conferring resistance to quinolones (qnrA), tetracyclines [tet(A)], sulfonamides (sul1, sul2), trimethoprim (dfrA12, dfrA14), rifampicin (arr-1), chloramphenicol (cmlA1, floR) and streptomycin (aadA1). The patient was placed under contact isolation precautions preventing the spread of this nearly untreatable pathogen.

Inactivation of the p53-KLF4-CEBPA Axis in Acute Myeloid Leukemia.

PURPOSE In acute myeloid leukemia (AML), the transcription factors CEBPA and KLF4 as well as the universal tumor suppressor p53 are frequently deregulated. Here, we investigated the extent of dysregulation, the molecular interactions, and the mechanisms involved. EXPERIMENTAL DESIGN One hundred ten AML patient samples were analyzed for protein levels of CEBPA, KLF4, p53, and p53 modulators. Regulation of CEBPA gene expression by KLF4 and p53 or by chemical p53 activators was characterized in AML cell lines. RESULTS We found that CEBPA gene transcription can be directly activated by p53 and KLF4, suggesting a p53-KLF4-CEBPA axis. In AML patient cells, we observed a prominent loss of p53 function and concomitant reduction of KLF4 and CEBPA protein levels. Assessment of cellular p53 modulator proteins indicated that p53 inactivation in leukemic cells correlated with elevated levels of the nuclear export protein XPO1/CRM1 and increase of the p53 inhibitors MDM2 and CUL9/PARC in the cytoplasm. Finally, restoring p53 function following treatment with cytotoxic chemotherapy compounds and p53 restoring non-genotoxic agents induced CEBPA gene expression, myeloid differentiation, and cell-cycle arrest in AML cells. CONCLUSIONS The p53-KLF4-CEBPA axis is deregulated in AML but can be functionally restored by conventional chemotherapy and novel p53 activating treatments. Clin Cancer Res; 22(3); 746-56. ©2015 AACR.

Antibiotic Susceptibility and Sequence Type Distribution of Ureaplasma Species Isolated from Genital Samples in Switzerland.

Antibiotic resistance in Ureaplasma urealyticum/Ureaplasma parvum and Mycoplasma hominis is an issue of increasing importance. However, data regarding the susceptibility and, more importantly, the clonality of these organisms are limited. We analyzed 140 genital samples obtained in Bern, Switzerland, in 2014. Identification and antimicrobial susceptibility tests were performed by using the Mycoplasma IST 2 kit and sequencing of 16S rRNA genes. MICs for ciprofloxacin and azithromycin were obtained in broth microdilution assays. Clonality was analyzed with PCR-based subtyping and multilocus sequence typing (MLST), whereas quinolone resistance and macrolide resistance were studied by sequencing gyrA, gyrB, parC, and parE genes, as well as 23S rRNA genes and genes encoding L4/L22 ribosomal proteins. A total of 103 samples were confirmed as positive for U. urealyticum/U. parvum, whereas 21 were positive for both U. urealyticum/U. parvum and M. hominis. According to the IST 2 kit, the rates of nonsusceptibility were highest for ciprofloxacin (19.4%) and ofloxacin (9.7%), whereas low rates were observed for clarithromycin (4.9%), erythromycin (1.9%), and azithromycin (1%). However, inconsistent results between microdilution and IST 2 kit assays were recorded. Various sequence types (STs) observed previously in China (ST1, ST2, ST4, ST9, ST22, and ST47), as well as eight novel lineages, were detected. Only some quinolone-resistant isolates had amino acid substitutions in ParC (Ser83Leu in U. parvum of serovar 6) and ParE (Val417Thr in U. parvum of serovar 1 and the novel Thr417Val substitution in U. urealyticum). Isolates with mutations in 23S rRNA or substitutions in L4/L22 were not detected. This is the first study analyzing the susceptibility of U. urealyticum/U. parvum isolates in Switzerland and the clonality outside China. Resistance rates were low compared to those in other countries. We hypothesize that some hyperepidemic STs spread worldwide via sexual intercourse. Large combined microbiological and clinical studies should address this important issue.

Water chemistry, and biological traits and mercury content of Salvelinus alpinus and S. namaycush in Laflamme and Pingualuit lake

Pingualuk Lake fills a deep crater in the Parc National des Pingualuit on the Ungava Peninsula (Nunavik, Canada) and is isolated from nearby surface waters. The main objectives of this study were to determine and compare the concentrations of two atmospherically derived contaminants, mercury and perfluorinated chemicals (PFCs), in the lake water column and fish of Pingualuk Lake and to assess the physical and biological factors influencing contaminant concentrations. Mercury concentrations in arctic char muscle tissue were comparable to those of char in other Arctic lakes, while the total amount of PFCs was below reported levels for remote lakes in the Arctic and elsewhere. Stable isotope and stomach content analyses were made to investigate the feeding ecology of the Pingualuk Lake arctic char population and indicated the possibility of multiple feeding groups. Genetics characteristics (MH and mtDNA) of fish from Pingualuk Lake revealed that this population is likely distinct from that of nearby Laflamme Lake. However, both arctic char populations exhibit differential variation of their allele families. Physical characteristics determined for Lake Pingualuk revealed that the water column was inversely stratified beneath the ice and extremely transparent to visible and ultraviolet radiation. The highest mercury concentrations (3- 6 pg/mL THg) occurred just beneath the ice surface in each lake. Pingualuk Lake, given its near pristine state and exceptional limnological features, may serve as a most valuable reference ecosystem for monitoring environmental stressors, such as contaminants, in the Arctic.

Región de Mendoza : Zona Este II : San Martín, Junín y Rivadavia

Regiones y Departamentos. Relatos de nuestra identidad es una serie que aborda las características turísticas, culturales e históricas de la provincia de Mendoza. En los 14 programas se han destacado y revalorizado las particularidades de cada uno de los departamentos de esta provincia argentina que se dividen en distintas regiones: Valle de Uco, Gran Mendoza, Zona Sur, Zona Este y Zona Nordeste ZONA ESTE II, es un documental que recorre los departamentos de San Martín, Junín y Rivadavia mostrando sus principales características sociales, turísticas y culturales. En el bloque 1 conoceremos la historia de Rivadavia, sus bodegas, personalidades y la famosa leyenda del anima parada. En el bloque 2 se destaca al departamento de San Martín, su actividad económica, social y deportiva. Finalmente en el bloque 3 se detalla la oferta turística y cultural de Rivadavia y Junin, culminando con un corto sobre la conocida "Rivadavia le canta al país".

Upper bound on neutrino mass based on T2K neutrino timing measurements

The Tokai to Kamioka (T2K) long-baseline neutrino experiment consists of a muon neutrino beam, produced at the J-PARC accelerator, a near detector complex and a large 295 km distant far detector. The present work utilizes the T2K event timing measurements at the near and far detectors to study neutrino time of flight as function of derived neutrino energy. Under the assumption of a relativistic relation between energy and time of flight, constraints on the neutrino rest mass can be derived. The sub-GeV neutrino beam in conjunction with timing precision of order tens of ns provide sensitivity to neutrino mass in the few MeV/c^2 range. We study the distribution of relative arrival times of muon and electron neutrino candidate events at the T2K far detector as a function of neutrino energy. The 90% C.L. upper limit on the mixture of neutrino mass eigenstates represented in the data sample is found to be m^2 < 5.6 MeV^2/c^4.

Measurement of the muon beam direction and muon flux for the T2K neutrino experiment

The Tokai-to-Kamioka (T2K) neutrino experiment measures neutrino oscillations by using an almost pure muon neutrino beam produced at the J-PARC accelerator facility. The T2K muon monitor was installed to measure the direction and stability of the muon beam which is produced together with the muon neutrino beam. The systematic error in the muon beam direction measurement was estimated, using data and MC simulation, to be 0.28 mrad. During beam operation, the proton beam has been controlled using measurements from the muon monitor and the direction of the neutrino beam has been tuned to within 0.3 mrad with respect to the designed beam-axis. In order to understand the muon beam properties, measurement of the absolute muon yield at the muon monitor was conducted with an emulsion detector. The number of muon tracks was measured to be (4.06 ± 0.05) × 10⁴ cm⁻² normalized with 4 × 10¹¹protons on target with 250 kA horn operation. The result is in agreement with the prediction which is corrected based on hadron production data.