955 resultados para OXA-48


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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.

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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.

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La diseminación de enterobacterias resistentes a los antibióticos carbapenémicos constituye una importante amenaza para los sistemas de salud. Las especies pertenecientes a la familia Enterobacteriaceae son la principal causa de infecciones relacionadas con la asistencia sanitaria, siendo los antibióticos carbapenémicos el último escalón terapéutico para una proporción cada vez mayor de pacientes con infecciones graves producidas por enterobacterias. La carbapenemasa OXA-48 es un enzima oxacilinasa con actividad hidrolítica para los antibióticos carbapenémicos que se describió por primera vez en un paciente hospitalizado en Turquía en el año 2001. Desde entonces las enterobacterias productoras de carbapenemasa OXA-48 han sido detectadas en numerosos países en el norte de África, Oriente Medio y Europa. Las enterobacterias productoras de carbapenemasa OXA-48 han estado implicadas en brotes nosocomiales y son un problema de gran trascendencia clínica. El gen que codifica para la carbapenemasa OXA-48 (blaOXA-48) forma parte del transposón Tn1999 que está flanqueado por dos copias de la secuencia de inserción IS1999...

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Background: In this study we describe the clinical and molecular characteristics of an outbreak due to carbapenem-resistant Klebsiella pneumoniae (CR-KP) producing CTX-M-15 and OXA-48 carbapenemase. Isogenic strains, carbapenem-susceptible K. pneumoniae (CS-KP) producing CTX-M-15, were also involved in the outbreak. Results: From October 2010 to December 2012 a total of 62 CR-KP and 23 CS-KP were isolated from clinical samples of 42 patients (22 had resistant isolates, 14 had susceptible isolates, and 6 had both CR and CS isolates). All patients had underlying diseases and 17 of them (14 patients with CR-KP and 3 with CS-KP) had received carbapenems previously. The range of carbapenem MICs for total isolates were: imipenem: 2 to >32 mu g/ml vs. <2 mu g/ml; meropenem: 4 to >32 mu g/ml vs. <2 mu g/ml; and ertapenem: 8 to >32 mu g/ml vs. <2 mu g/ml. All the isolates were also resistant to gentamicin, ciprofloxacin, and cotrimoxazole. Both types of isolates shared a common PFGE pattern associated with the multilocus sequence type 101 (ST101). The bla(CTX-M-15) gene was detected in all the isolates, whereas the bla(OXA-48) gene was only detected in CR-KP isolates on a 70 kb plasmid. Conclusions: The clonal spread of K. pneumoniae ST101 expressing the OXA-48 and CTX-M-15 beta-lactamases was the cause of an outbreak of CR-KP infections. CTX-M-15-producing isolates lacking the blaOXA-48 gene coexisted during the outbreak.

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Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis patients. This study compares the antimicrobial susceptibility of 153 P. aeruginosa isolates from the United Kingdom (UK) (n=58), Belgium (n=44), and Germany (n=51) collected from 120 patients during routine visits over the 2006-2012 period. MICs were measured by broth microdilution. Genes encoding extended spectrum β-lactamases (ESBL), metallo-β-lactamases and carbapenemases were detected by PCR. Pulsed Field Gel Electrophoresis and Multi-Locus Sequence Typing were performed on isolates resistant to ≥ 3 antibiotic classes among penicillins/cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, polymyxins. Based on EUCAST/CLSI breakpoints, susceptibility was ≤ 30%/≤ 40% (penicillins, ceftazidime, amikacin, ciprofloxacin), 44-48%/48-63% (carbapenems), 72%/72% (tobramycin), and 92%/78% (colistin) independently of patient's age. Sixty percent of strains were multidrug resistant (MDR; European Centre for Disease prevention and Control criteria). Genes encoding ESBL (most prevalent BEL, PER, GES, VEB, CTX-M, TEM, SHV, and OXA), metallo β-lactamases (VIM, IMP, NDM), or carbapenemases (OXA-48, KPC) were not detected. The Liverpool Epidemic Strain (LES) was prevalent in UK isolates only (75% of MDR isolates). Four MDR ST958 isolates were found spread over the three countries. The other MDR clones were evidenced in ≤ 3 isolates and localized in a single country. A new sequence type (ST2254) was discovered in one MDR isolate in Germany. Clonal and non-clonal isolates with different susceptibility profiles were found in 21 patients. Thus, resistance and MDR are highly prevalent in routine isolates from 3 countries, with carbapenem (meropenem), tobramycin and colistin remaining the most active drugs.

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The discovery of antibiotics was a major breakthrough in medicine. However, short after their introduction in clinical practice resistant bacteria were detected. Nowadays, antibiotic resistance constitutes a serious public health problem. In hospital settings, with high resistance levels, reducing drastically the therapeutic options. Carbapenems are last-resort antibiotics used in Portugal, only in hospitals, to treat serious infections. Bacterial resistance towards this class of antibiotics has increased during last years. In Gram-negative bacteria the production of carbapenemases is a common resistance mechanism. OXA-48 is a carbapenemase of Ambler class D and represents a major concern for human health. It is frequently detected in clinical isolates of Enterobacteriaceae. There are few studies suggesting that genes encoding for OXA-48 variants originated from genes present in the chromosome of members of genus Shewanella, and have disseminated to Enterobacteriaceae members, associated with mobile genetic elements. The aim of this study was to characterize strains from different sources of Shewanella to confirm its role as OXA-48 progenitor. For this, the phylogenetic affiliation of 33 strains of Shewanella was performed by 16SrDNA and gyrB sequencing. The most common species were S. hafniensis and S. xiamenensis, but also S. aestuarii, S. baltica, S. indica, S. haliotis, S. putrefaciens, S. algidipiscicola, S. irciniae, S. algae and S. fodinae were identified. blaOXA-48-like genes were detected in 21 isolates: S. hafniensis (8/8), S. xiamenensis (5/5), S. baltica (4/4), S. algae (1/1), S. fodinae (1/1), S. putrefaciens (1/2) and S. algidipiscicola (1/2). Sequence analysis revealed that genes encoded enzymes identical to OXA-48, OXA-181 and OXA-204 but also new variants differing from OXA-48 from 2 to 81 aminoacids. Genetic context analysis revealed the C15 gene upstream and lysR gene downstream, identical to what has been identified so far flanking blaOXA-48-like genes in Shewanella spp. The assessment of antibiotic susceptibility was performed for all isolates using the disk diffusion method. In general, it was observed a great sensitivity for all antibiotics except to amoxicillin and aztreonam. Multidrug resistance was detected in only 1 isolate. Other resistance genes and the presence of integrons were not identified. Plasmids were detected in 30.3% isolates (10/ 33). These results reinforce the role of Shewanella spp. as origin of blaOXA-48-like genes.

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Seven Klebsiella pneumoniae isolates from dogs and cats in Spain were found to be highly resistant to aminoglycosides, and ArmA methyltransferase was responsible for this phenotype. All isolates were typed by multilocus sequence typing (MLST) as ST11, a human epidemic clone reported worldwide and associated with, among others, OXA-48 and NDM carbapenemases. In the seven strains, armA was borne by an IncR plasmid, pB1025, of 50 kb. The isolates were found to coproduce DHA-1 and SHV-11 β-lactamases, as well as the QnrB4 resistance determinant. This first report of the ArmA methyltransferase in pets illustrates their importance as a reservoir for human multidrug-resistant K. pneumoniae.

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The 48 hour game making challenge has been running since its inception at the NEXT LEVEL Festival in 2004. It is curated by Truna aka j. Turner and Lubi Thomas and sees teams of both future game makers and industry professionals going head to head under pressure to produce playable games within the time period. The 48 hour is supported by the International Game Developers Association (Brisbane Chapter)and the Creative Industries Precincts as part of their public programs. It is a curated event which engages industry with Brisbane educational institutes and which fosters the Australian Games Industry

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Performance / Event Documentation and Curatorial Research Statement

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Statement: Jams, Jelly Beans and the Fruits of Passion Let us search, instead, for an epistemology of practice implicit in the artistic, intuitive processes which some practitioners do bring to situations of uncertainty, instability, uniqueness, and value conflict. (Schön 1983, p40) Game On was born out of the idea of creative community; finding, networking, supporting and inspiring the people behind the face of an industry, those in the mist of the machine and those intending to join. We understood this moment to be a pivotal opportunity to nurture a new emerging form of game making, in an era of change, where the old industry models were proving to be unsustainable. As soon as we started putting people into a room under pressure, to make something in 48hrs, a whole pile of evolutionary creative responses emerged. People refashioned their craft in a moment of intense creativity that demanded different ways of working, an adaptive approach to the craft of making games – small – fast – indie. An event like the 48hrs forces participants’ attention on the process as much as the outcome. As one game industry professional taking part in a challenge for the first time observed: there are three paths in the genesis from idea to finished work: the path that focuses on mechanics; the path that focuses on team structure and roles and the path that focuses on the idea, the spirit – and the more successful teams need to put the spirit of the work first and foremost. The spirit drives the adaptation, it becomes improvisation. As Schön says: “Improvisation consists on varying, combining and recombining a set of figures within the schema which bounds and gives coherence to the performance.” (1983, p55). This improvisational approach is all about those making the games: the people and the principles of their creative process. This documentation evidences the intensity of their passion, determination and the shit that they are prepared to put themselves through to achieve their goal – to win a cup full of jellybeans and make a working game in 48hrs. 48hr is a project where, on all levels, analogue meets digital. This concept was further explored through the documentation process. This set of four videos were created by Cameron Owen on the fly during the challenge using both the iphone video camera and editing software in order to be available with immediacy and allow the event audience to share the experience - and perhaps to give some insights into the creative process exposed by the 48 hour challenge. ____________________________ Schön, D. A. 1983, The Reflective Practitioner: How Professionals Think in Action, Basic Books, New York

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Germline mutations within the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and one of its targets, the cyclin dependent kinase 4 (CDK4) gene, have been identified in a proportion of melanoma kindreds. In the case of CDK4, only one specific mutation, resulting in the substitution of a cysteine for an arginine at codon 24 (R24C), has been found to be associated with melanoma. We have previously reported the identification of germline CDKN2A mutations in 7/18 Australian melanoma kindreds and the absence of the R24C CDK4 mutation in 21 families lacking evidence of a CDKN2A mutation. The current study represents an expansion of these efforts and includes a total of 48 melanoma families from Australia. All of these families have now been screened for mutations within CDKN2A and CDK4, as well as for mutations within the CDKN2A homolog and 9p21 neighbor, the CDKN2B gene, and the alternative exon 1 (E1beta) of CDKN2A. Families lacking CDKN2A mutations, but positive for a polymorphism(s) within this gene, were further evaluated to determine if their disease was associated with transcriptional silencing of one CDKN2A allele. Overall, CDKN2A mutations were detected in 3/30 (10%) of the new kindreds. Two of these mutations have been observed previously: a 24 bp duplication at the 5' end of the gene and a G to C transversion in exon 2 resulting in an M531 substitution. A novel G to A transition in exon 2, resulting in a D108N substitution was also detected. Combined with our previous findings, we have now detected germline CDKN2A mutations in 10/48 (21%) of our melanoma kindreds. In none of the 'CDKN2A-negative' families was melanoma found to segregate with either an untranscribed CDKN2A allele, an R24C CDK4 mutation, a CDKN2B mutation, or an E1beta mutation. The last three observations suggest that these other cell cycle control genes (or alternative gene products) are either not involved at all, or to any great extent, in melanoma predisposition.

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The 48-hour game making challenge started out in 2007 as a creative community event. We have run this event each year since and seen over 120 games made. 2011 was the most remarkable in that each of the 20 teams made a playable game – the shape of the challenge has changed …. We have invested in the process of reflective practice & action research, with the event being part of a sweep of programs that inform this research, with each year giving us fresh insights into both the creative practice and essential concerns, process and trends of the independent games industry creative community, which we then respond to within our curatorial development of the subsequent programming. The 2011 48-hour challenge research project focused on the people and the site. We were specifically interested in the manner in which the community occupied the creative space.

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We have always felt that “something very special” was happening in the 48hr and other similar game jams. This “something” is more than the intensity and challenge of the experience, although this certainly has appeal for the participants. We had an intuition that these intense 48 hour game jams exposed something pertinent to the changing shape of the Australian games industry where we see the demise of the late 20th century large studio - the “Night Elf” model and the growth of the small independent model. There are a large number of wider economic and cultural factors around this evolution but our interest is specifically in the change from “industry” to “creative industry” and the growth of games as a cultural media and art practice. If we are correct in our intuition, then illuminating this something also has important ramifications for those courses which teach game and interaction design and development. Rather than undertake a formal ethno-methodological approach, we decided to track as many of the actors in the event as possible. We documented the experience (Keith Novak’s beautiful B&W photography), the individual and their technology (IOGraph mouse tracking), the teams as a group (Time lapse photography) and movement tracking throughout the whole space (Blue tooth phone tracking). The raw data collected has given us opportunity to start a commentary on the “something special” happening in the 48hr.

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Persistent digital hyperthermia, presumably due to vasodilation, occurs during the developmental and acute stages of insulin-induced laminitis. The objectives of this study were to determine if persistent digital hyperthermia is the principal pathogenic mechanism responsible for the development of laminitis. The potent vasodilator, ATP-MgCl 2 was infused continuously into the distal phalanx of the left forefoot of six Standardbred racehorses for 48h via intra-osseous infusion to promote persistent digital hyperthermia. The right forefoot was infused with saline solution and acted as an internal control. Clinical signs of lameness at the walk were not detected at 0h, 24h or 48h post-infusion. Mean±SE hoof wall temperatures of the left forefoot (29.4±0.25°C) were higher (P<0.05) than those on the right (27.5±0.38°C). Serum insulin (15.0±2.89μIU/mL) and blood glucose (5.4±0.22mM) concentrations remained unchanged during the experiment. Histopathological evidence of laminitis was not detected in any horse. The results demonstrated that digital vasodilation up to 30 °C for a period of 48. h does not trigger laminitis in the absence of hyperinsulinaemia. Thus, although digital hyperthermia may play a role in the pathogenesis of laminitis, it is not the sole mechanism involved.