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https://www.readbyqxmd.com/read/28102514/carbapenemase-producing-klebsiella-pneumoniae-bloodstream-infection-in-critically-ill-patients-risk-factors-and-predictors-of-mortality
#1
M Papadimitriou-Olivgeris, F Fligou, C Bartzavali, A Zotou, A Spyropoulou, K Koutsileou, S Vamvakopoulou, N Sioulas, V Karamouzos, E D Anastassiou, I Spiliopoulou, M Christofidou, M Marangos
A significant increase in carbapenemase-producing Klebsiella pneumoniae (CP-Kp) bacteraemias has been observed worldwide. The objective of the present work was to study the risk factors and predictors of mortality of CP-Kp bacteraemias among critically ill patients. During a 4-year period (2012-3015), a matched 1:2 case-control study was conducted. Klebsiella pneumoniae was identified by Vitek 2 technology. Antibiotic susceptibility was performed by the agar disc diffusion method and Etest. The presence of the bla KPC, bla VIM and bla NDM genes was confirmed by polymerase chain reaction (PCR)...
January 19, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28096418/multi-institute-analysis-of-carbapenem-resistance-reveals-remarkable-diversity-unexplained-mechanisms-and-limited-clonal-outbreaks
#2
Gustavo C Cerqueira, Ashlee M Earl, Christoph M Ernst, Yonatan H Grad, John P Dekker, Michael Feldgarden, Sinéad B Chapman, João L Reis-Cunha, Terrance P Shea, Sarah Young, Qiandong Zeng, Mary L Delaney, Diane Kim, Ellena M Peterson, Thomas F O'Brien, Mary Jane Ferraro, David C Hooper, Susan S Huang, James E Kirby, Andrew B Onderdonk, Bruce W Birren, Deborah T Hung, Lisa A Cosimi, Jennifer R Wortman, Cheryl I Murphy, William P Hanage
Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095794/development-of-an-algorithm-for-phenotypic-screening-of-carbapenemase-producing-enterobacteriaceae-in-the-routine-laboratory
#3
Jérôme Robert, Alix Pantel, Audrey Merens, Elodie Meiller, Jean-Philippe Lavigne, Marie-Hélène Nicolas-Chanoine
BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) are difficult to identify among carbapenem non-susceptible Enterobacteriaceae (NSE). We designed phenotypic strategies giving priority to high sensitivity for screening putative CPE before further testing. METHODS: Presence of carbapenemase-encoding genes in ertapenem NSE (MIC > 0.5 mg/l) consecutively isolated in 80 French laboratories between November 2011 and April 2012 was determined by the Check-MDR-CT103 array method...
January 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28092668/upregulation-of-ret-induces-perineurial-invasion-of-pancreatic-adenocarcinoma
#4
M Amit, S Na'ara, L Leider-Trejo, Y Binenbaum, N Kulish, E Fridman, A Shabtai-Orbach, R J Wong, Z Gil
Tumor spread along nerves, a phenomenon known as perineurial invasion, is common in various cancers including pancreatic ductal adenocarcinoma (PDAC). Neural invasion is associated with poor outcome, yet its mechanism remains unclear. Using the transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we investigated the mechanism of neural invasion in PDAC. To detect tissue-specific factors that influence neural invasion by cancer cells, we characterized the perineurial microenvironment using a series of bone marrow transplantation (BMT) experiments in transgenic mice expressing single mutations in the Cx3cr1, GDNF and CCR2 genes...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28089736/antibacterial-activity-of-limonium-brasiliense-baicuru-against-multidrug-resistant-bacteria-using-a-statistical-mixture-design
#5
Andressa Blainski, Barbara Gionco, Admilton G Oliveira, Galdino Andrade, Ieda S Scarminio, Denise B Silva, Norberto P Lopes, João C P Mello
ETHNOPHARMACOLOGICAL RELEVANCE: Limonium brasiliense (Boiss.) Kuntze (Plumbaginaceae) is commonly known as "baicuru" or "guaicuru" and preparations of its dried rhizomes have been populary used in the treatment of premenstrual syndrome and menstrual disorder, and as an antiseptic in genito-urinary infections. This study evaluated the potential antibacterial activity of rhizome extracts against multidrug-resistant bacterial strains using statistical mixture design. MATERIALS AND METHODS: The statistical design of four components (water, methanol, acetone and ethanol) produced 15 different extracts and also a confirmatory experiment, which was performed using water:acetone (3:7, v/v)...
January 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28081233/differences-in-inflammatory-response-induced-by-two-representatives-of-clades-of-the-pandemic-st258-klebsiella-pneumoniae-clonal-lineage-producing-kpc-type-carbapenemases
#6
Giuseppe Castronovo, Ann Maria Clemente, Alberto Antonelli, Marco Maria D'Andrea, Michele Tanturli, Eloisa Perissi, Sara Paccosi, Astrid Parenti, Federico Cozzolino, Gian Maria Rossolini, Maria Gabriella Torcia
ST258-K. pneumoniae (ST258-KP) strains, the most widespread multidrug-resistant hospital-acquired pathogens, belong to at least two clades differing in a 215 Kb genomic region that includes the cluster of capsule genes. To investigate the effects of the different capsular phenotype on host-pathogen interactions, we studied representatives of ST258-KP clades, KKBO-1 and KK207-1, for their ability to activate monocytes and myeloid dendritic cells from human immune competent hosts. The two ST258-KP strains strongly induced the production of inflammatory cytokines...
2017: PloS One
https://www.readbyqxmd.com/read/28077701/a-comparison-of-eleven-phenotypic-assays-for-the-accurate-detection-of-carbapenemase-producing-enterobacteriaceae
#7
Pranita D Tamma, Belita N A Opene, Andrew Gluck, Krizia K Chambers, Karen C Carroll, Patricia J Simner
BACKGROUND: Early identification of carbapenemase-producing Enterobacteriaceae (CPE) is essential to prevent their dissemination within healthcare settings. Our objective was to evaluate the accuracy of 11 phenotypic assays for the detection of CPE. METHODS: Two collections of carbapenem-resistant Enterobacteriaceae (CRE) isolates were evaluated including 191 retrospective isolates (122 CP-CRE and 69 non-CP isolates) as well as 45 prospective clinical isolates (15 CP-CRE and 30 non-CP-CRE) obtained over a 3-month period...
January 11, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#8
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28072891/molecular-epidemiology-and-resistome-analysis-of-multidrug-resistant-st11-klebsiella-pneumoniae-strain-containing-multiple-copies-of-extended-spectrum-%C3%AE-lactamase-genes-using-whole-genome-sequencing
#9
Roshan DSouza, Naina Adren Pinto, Insik Hwang, Hwang Younjee, YoungLag Cho, Hyunsoo Kim, Dongeun Yong, Jongrak Choi, Kyungwon Lee, Yunsop Chong
The aim of this work was to investigate the mechanism responsible for multidrug resistance in ST11 Klebsiella pneumoniae YMC 2013/7/B3993 containing multiple copies of ESBL genes using multiple parallel sequencing technology. In-depth analysis of the strain revealed multiple copies of ESBL genes, 2 copies of blaSHV-12 and 1 copy of blaCTX-M-15. Furthermore, 1 copy of blaOXA-9 and 3 copies of blaTEM-1 were found. The insertion of Tn1331 was detected, which consisted of blaOXA-9, blaTEM-1, aac(6')-lb-cr, and aadA1 genes...
January 10, 2017: New Microbiologica
https://www.readbyqxmd.com/read/28069651/inhibition-by-avibactam-and-clavulanate-of-the-%C3%AE-lactamases-kpc-2-and-ctx-m-15-harboring-the-substitution-n132g-in-the-conserved-motif-sdn
#10
Clément Ourghanlian, Daria Soroka, Michel Arthur
The substitution N(132)G in the motif SDN of class A β-lactamases from rapidly-growing mycobacteria was previously shown to impair their inhibition by avibactam but to improve the stability of acyl-enzymes formed with clavulanate. The same substitution was introduced in KPC-2 and CTX-M-15 to assess its impact on β-lactamases from Enterobacteriaceae and evaluate whether it could lead to resistance to the ceftazidime-avibactam combination. Kinetic parameters for the inhibition of the β-lactamases by avibactam and clavulanate were determined by spectrophotometry using nitrocefin as the substrate...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28069649/antimicrobial-activity-of-ceftazidime-avibactam-when-tested-against-gram-negative-bacteria-isolated-from-patients-hospitalized-with-pneumonia-in-united-states-medical-centers-2011-2015
#11
Helio S Sader, Mariana Castanheira, Robert K Flamm
Bacterial isolates were collected from patients hospitalized with pneumonia (PHP), including ventilator-associated (VAP), from 76 USA medical centers in 2011-2015. The Gram-negative organisms (n=11,185; including 1,097 from VAP) were tested for susceptibility against ceftazidime-avibactam and comparators by broth microdilution method. β-lactamase-encoding genes were screened using a microarray based assay on selected isolates. Pseudomonas aeruginosa and Klebsiella spp. were the most common Gram-negatives isolated from PHP and VAP...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28065546/discharge-of-kpc-2-genes-from-the-wwtps-contributed-to-their-enriched-abundance-in-the-receiving-river
#12
Fengxia Yang, Liang Huang, Linyun Li, Yang Yang, Daqing Mao, Yi Luo
At present, very little is known about the persistence and spread pathway of KPC-2 genes in the environment. Our previous study reported the prevalence and persistence of KPC-2 genes in wastewater treatment plants (WWTPs). In the present work, we investigated the occurrence and fate of KPC-2 genes in a WWTP discharge-receiving river and studied the effect of WWTP discharges on the prevalence of KPC-2 genes and host bacteria in the receiving river. It is observed that a considerable level of KPC-2 genes occurred in the receiving river, and a significant increase of blaKPC-2 abundance in the downstream following WWTP discharge was observed compared to the upstream...
January 5, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28049378/isolation-of-escherichia-coli-st131-producing-kpc-2-in-bulgaria
#13
Rumyana Markovska, Temenuga Stoeva, Lyudmila Boyanova, Petya Stankova, Daniela Pencheva, Radka Kaneva, Vanyo Mitev, Ivan Mitov
No abstract text is available yet for this article.
January 3, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28046730/su-f-j-07-evaluating-the-adequacy-of-biopsy-specimens-for-genetic-signature-assessment-by-measuring-the-metabolic-activity-in-specimens-obtained-under-18f-fdg-pet-ct-guidance
#14
L Fanchon, J Russell, S Dogan, S Carlin, K Pinker-Domenig, E Yorke, C Ross Schmidtlein, S Fujisawa, K Manova-Todorova, P Zanzonico, J O Deasy, J L Humm, S Solomon, A S Kirov
PURPOSE: Genetic profiling of biopsied tissue is the basis for personalized cancer therapy. However biopsied materials may not contain sufficient amounts of DNA needed for analysis. We propose a method to determine the adequacy of specimens for performing genetic profiling by quantifying metabolic activity. METHODS: We measured the response of two radiation detectors to the activity contained in the minimum amount of tumor cells needed for genetic profiling in biopsy specimens obtained under 2-deoxy-2-((18) F)fluoro-D-glucose ((18) F-FDG) PET/CT guidance...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28040408/polymyxin-b-in-combination-with-meropenem-against-carbapenemase-producing-klebsiella-pneumoniae-pharmacodynamics-and-morphological-changes
#15
Rajnikant Sharma, Saloni Patel, Cely Abboud, John Diep, Neang S Ly, Jason M Pogue, Keith S Kaye, Jian Li, Gauri G Rao
Combination therapy provides a useful therapeutic approach to overcome resistance until new antibiotics become available. In this study, the pharmacodynamics, including the morphological effects, of polymyxin B (PMB) and meropenem alone and in combination against KPC-producing Klebsiella pneumoniae clinical isolates was examined. Ten clinical isolates were obtained from patients undergoing treatment for mediastinitis. KPCs were identified and MICs were measured using microbroth dilution. Time-kill studies were conducted over 24 h with PMB (0...
December 23, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28039276/the-pharmacodynamics-of-avibactam-in-combination-with-ceftaroline-or-ceftazidime-against-%C3%AE-lactamase-producing-enterobacteriaceae-studied-in-an-in-vitro-model-of-infection
#16
Alasdair MacGowan, Sharon Tomaselli, Alan Noel, Karen Bowker
OBJECTIVES: Pharmacodynamics of β-lactamase inhibitors are an area of intense interest as new β-lactam/β-lactamase inhibitor combinations enter clinical development and clinical practice. Avibactam, a non-β-lactam β-lactamase inhibitor, has been combined with ceftaroline or ceftazidime but these two combinations have not been directly compared. METHODS: Using an in vitro pharmacokinetic model we simulated human drug concentration-time courses associated with ceftaroline 600 mg every 8 h and ceftazidime 2000 mg every 8 h...
December 30, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28035373/cancer-associated-peritoneal-mesothelial-cells-lead-the-formation-of-pancreatic-cancer-peritoneal-dissemination
#17
Toshiya Abe, Kenoki Ohuchida, Kazuhiro Koikawa, Sho Endo, Takashi Okumura, Masafumi Sada, Kohei Horioka, Biao Zheng, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Tatsuya Manabe, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Makoto Hashizume, Masafumi Nakamura
The interaction between the cancer cells and the peritoneal mesothelial cells (PMCs) plays an important role in the peritoneal dissemination in several types of cancer. However, the role of PMCs in the peritoneal dissemination of pancreatic cancer remains unclear. In the present study, we investigated the interaction between the pancreatic cancer cells (PCCs) and the PMCs in the formation of peritoneal dissemination in vitro and in vivo. The tumor-stromal interaction of PCCs and PMCs significantly enhanced their mobility and invasiveness and enhanced the proliferation and anoikis resistance of PCCs...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28031433/comparison-of-phenotypic-tests-and-an-immunochromatographic-assay-and-development-of-a-new-algorithm-for-oxa-48-like-detection
#18
Florian Koroska, Stephan Göttig, Martin Kaase, Jörg Steinmann, Sören Gatermann, Julian Sommer, Thorsten Wille, Georg Plum, Axel Hamprecht
OXA-48 is the most prevalent carbapenemase in Enterobacteriaceae in Europe and the Middle East, but is frequently missed because many isolates display low minimal inhibitory concentrations (MIC) for carbapenems. Furthermore, in contrast to metallo-β-lactamases or Klebsiella pneumoniae carbapenemases (KPC), no specific inhibitor is available for the phenotypic detection of OXA-48. Molecular detection of blaOXA-48 is the gold standard, but is not available in many laboratories. Few phenotypic assays have been described, but have not been independently evaluated...
December 28, 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28031201/emergence-of-ceftazidime-avibactam-resistance-due-to-plasmid-borne-blakpc-3-mutations-during-treatment-of-carbapenem-resistant-klebsiella-pneumoniae-infections
#19
Ryan K Shields, Liang Chen, Shaoji Cheng, Kalyan D Chavda, Ellen G Press, Avin Snyder, Ruchi Pandey, Yohei Doi, Barry N Kreiswirth, M Hong Nguyen, Cornelius J Clancy
Ceftazidime-avibactam is a novel β-lactam/β-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae (CRE) that produce Klebsiella pneumoniae carbapenemase (KPC). We report the first cases of ceftazidime-avibactam resistance to develop during treatment of CRE infections, and identify resistance mechanisms. Ceftazidime-avibactam resistant K. pneumoniae emerged in three patients after ceftazidime-avibactam treatment for 10-19 days. Whole genome sequencing (WGS) of longitudinal ceftazidime-avibactam susceptible and resistant K...
December 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28031200/low-frequency-of-ceftazidime-avibactam-resistance-among-enterobacteriaceae-isolates-carrying-blakpc-collected-in-hospitals-from-the-united-states-from-2012-to-2015
#20
Mariana Castanheira, Rodrigo E Mendes, Helio S Sader
KPC-producing Enterobacteriaceae isolates have been increasingly reported worldwide and therapeutic options to treat infections caused by these organisms are limited. We evaluated the activity of ceftazidime-avibactam and comparators against 456 Enterobacteriaceae isolates carrying blaKPC collected from 79 United States hospitals during 2012-2015. Overall, ceftazidime-avibactam (MIC50/90, 0.5/2 μg/mL; 99.3% susceptible) and tigecycline (MIC50/90, 0.5/1 μg/mL; 98.9% at ≤2 μg/mL) were the most active agents...
December 28, 2016: Antimicrobial Agents and Chemotherapy
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