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https://www.readbyqxmd.com/read/29730830/the-epidemiology-evolution-and-treatment-of-kpc-producing-organisms
#1
REVIEW
Ann Marie Porreca, Kaede V Sullivan, Jason C Gallagher
PURPOSE OF REVIEW: The purpose of this review is to investigate the evolution and epidemiology of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and the current and future treatment options for infections caused by KPC-producing isolates. RECENT FINDINGS: The emergence of resistance in Enterobacteriaceae producing carbapenemases globally has increased the challenges in treating infections caused by these organisms. One of the prominent mechanisms of resistance is the production of KPC enzymes...
May 5, 2018: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/29692574/phenotypic-and-genotypic-characterization-of-carbapenem-resistance-mechanisms-in-klebsiella-pneumoniae-from-blood-culture-specimens-a-study-from-north-india
#2
Varsha Gupta, Ritu Garg, Karthikeyan Kumaraswamy, Priya Datta, Gursimran Kaur Mohi, Jagdish Chander
BACKGROUND: Emergence of carbapenem resistance among Enterobacteriaceae in different geographical regions is of great concern as these bacteria are easily transmissible among patients. Carbapenem-resistance in Enterobacteriaceae is due to production of carbapenemases of various classes and hyper production of the ESBLs (Extended spectrum beta lactamases) and Amp C beta lactamases with reduced cell wall permeability mechanisms. Phenotypic detection and differentiation is important for proper infection control and appropriate patient management...
April 2018: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/29683461/utilizing-high-resolution-ultrasound-to-monitor-tumor-onset-and-growth-in-genetically-engineered-pancreatic-cancer-models
#3
Robert-Guenther Goetze, Soeren M Buchholz, Shilpa Patil, Golo Petzold, Volker Ellenrieder, Elisabeth Hessmann, Albrecht Neesse
The LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre (KPC) mouse model represents an established and frequently used transgenic model to evaluate novel therapies in pancreatic cancer. Tumor onset is variable in the KPC model between 8 weeks and several months. Therefore, non-invasive imaging tools are required to screen for tumor onset and monitor for response to treatment. To address this issue, different approaches have emerged over the last years. High resolution ultrasound has major advantages such as non-invasiveness, fast session times and a high image resolution without radiation exposure...
April 7, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29675006/the-rapid-emergence-of-tigecycline-resistance-in-bla-kpc-2-harboring-klebsiella-pneumoniae-as-mediated-in-vivo-by-mutation-in-teta-during-tigecycline-treatment
#4
Xiaoxing Du, Fang He, Qiucheng Shi, Feng Zhao, Juan Xu, Ying Fu, Yunsong Yu
Tigecycline is one of the last resort treatments for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. Tigecycline resistance often occurs during the clinical treatment of CRKP, yet its mechanism has still not been clearly elucidated. This study presents an analysis of a tigecycline resistance mechanism that developed in clinical isolates from a 56-year-old female patient infected with CRKP during tigecycline treatment. Consecutive clonal consistent K. pneumoniae isolates were obtained during tigecycline treatment...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29669760/rho-kinase-inhibition-by-at13148-blocks-pancreatic-ductal-adenocarinoma-invasion-and-tumor-growth
#5
Nicola Rath, June Munro, Marie Fa Cutiongco, Alicja Jagiełło, Nikolaj Gadegaard, Lynn McGarry, Mathieu Unbekandt, Evdokia Michalopoulou, Jurre J Kamphorst, David Sumpton, Gillian Mackay, Claire Vennin, Marina Pajic, Paul Timpson, Michael F Olson
The high mortality of pancreatic cancer demands that new therapeutic avenues be developed. The orally available small molecule inhibitor AT13148 potently inhibits ROCK1 and ROCK2 kinases that regulate the actomyosin cytoskeleton. We previously reported that ROCK kinase expression increases with human and mouse pancreatic cancer progression and that conditional ROCK activation accelerates mortality in a genetically modified LSL-KrasG12D; LSL-p53R172H; Pdx1-Cre; (KPC) mouse pancreatic cancer model. In this study, we show that treatment of KPC mouse and human TKCC5 patient-derived pancreatic tumor cells with AT13148, as well as the ROCK selective inhibitors Y27632 and H1152, act comparably in blocking ROCK substrate phosphorylation...
April 18, 2018: Cancer Research
https://www.readbyqxmd.com/read/29657865/stress-adaptive-responses-associated-with-high-level-carbapenem-resistance-in-kpc-producing-klebsiella-pneumoniae
#6
Sheila Adams-Sapper, Adam Gayoso, Lee W Riley
Carbapenem-resistant Enterobacteriaceae (CRE) organisms have emerged to become a major global public health threat among antimicrobial resistant bacterial human pathogens. Little is known about how CREs emerge. One characteristic phenotype of CREs is heteroresistance, which is clinically associated with treatment failure in patients given a carbapenem. Through in vitro whole-transcriptome analysis we tracked gene expression over time in two different strains (BR7, BR21) of heteroresistant KPC-producing Klebsiella pneumoniae, first exposed to a bactericidal concentration of imipenem followed by growth in drug-free medium...
2018: Journal of Pathogens
https://www.readbyqxmd.com/read/29627985/strategic-approaches-to-overcome-resistance-against-gram-negative-pathogens-using-%C3%AE-lactamase-inhibitors-and-%C3%AE-lactam-enhancers-activity-of-three-novel-diazabicyclooctanes-wck-5153-zidebactam-wck-5107-and-wck-4234
#7
Krisztina M Papp-Wallace, Nhu Q Nguyen, Michael R Jacobs, Christopher R Bethel, Melissa D Barnes, Vijay Kumar, Saralee Bajaksouzian, Susan D Rudin, Philip N Rather, Satish Bhavsar, Tadiparthi Ravikumar, Prasad K Deshpande, Vijay Patil, Ravindra Yeole, Sachin S Bhagwat, Mahesh V Patel, Focco van den Akker, Robert A Bonomo
Limited treatment options exist to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria possessing broad-spectrum β-lactamases. The design of novel β-lactamase inhibitors is of paramount importance. Here, three novel diazabicyclooctanes (DBOs), WCK 5153, zidebactam (WCK 5107), and WCK 4234 (compounds 1-3, respectively), were synthesized and biochemically characterized against clinically important bacteria. Compound 3 inhibited class A, C, and D β-lactamases with unprecedented k2 / K values against OXA carbapenemases...
April 20, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29610205/relebactam-is-a-potent-inhibitor-of-the-kpc-2-%C3%AE-lactamase-and-restores-the-susceptibility-of-imipenem-against-kpc-producing-enterobacteriaceae
#8
Krisztina M Papp-Wallace, Melissa D Barnes, Jim Alsop, Magdalena A Taracila, Christopher R Bethel, Scott A Becka, David van Duin, Barry N Kreiswirth, Keith S Kaye, Robert A Bonomo
The imipenem-relebactam combination is in development as a potential treatment regimen for infections caused by Enterobacteriaceae possessing complex β-lactamase backgrounds. Relebactam is a β-lactamase inhibitor that possesses the diazabicyclooctane core similar to avibactam, however relebactam's R1 side chain also includes a piperidine ring compared to the carboxyamide of avibactam. Here, we investigated the inactivation of Klebsiella pneumoniae carbapenemase (KPC-2), the most widespread class A carbapenemase, by relebactam and performed susceptibility testing with imipenem-relebactam using KPC-producing clinical isolates of Enterobacteriaceae...
April 2, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29566151/in-vivo-evolution-of-resistant-subpopulations-of-kpc-producing-klebsiella-pneumoniae-during-ceftazidime-avibactam-treatment
#9
Paolo Gaibani, Caterina Campoli, Russell E Lewis, Silvia Lidia Volpe, Erika Scaltriti, Maddalena Giannella, Stefano Pongolini, Andrea Berlingeri, Francesco Cristini, Michele Bartoletti, Sara Tedeschi, Simone Ambretti
Objectives: KPC-producing Klebsiella pneumoniae (KPC-Kp) represent a serious problem worldwide. Herein, we describe the evolution of ceftazidime/avibactam resistance by sequencing longitudinal clinical isolates from a patient with KPC-Kp bloodstream infection undergoing ceftazidime/avibactam treatment. Methods: WGS was performed on one ceftazidime/avibactam-susceptible KPC-Kp (BOT-CA-S) and two phenotypically different ceftazidime/avibactam-resistant KPC-Kp with low (BOT-CA-R) and high (BOT-EMO) carbapenem MICs...
March 16, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29558475/molecular-epidemiology-and-drug-resistant-mechanism-in-carbapenem-resistant-klebsiella-pneumoniae-isolated-from-pediatric-patients-in-shanghai-china
#10
Xingyu Zhang, Di Chen, Guifeng Xu, Weichun Huang, Xing Wang
Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center...
2018: PloS One
https://www.readbyqxmd.com/read/29540262/colistin-resistant-kpc-2-producing-klebsiella-pneumoniae-st423-harboring-an-is5-like-element-in-the-mgrb-gene-isolated-from-cerebrospinal-fluid
#11
Hemilly Rayanne Ferreira da Silva, Marinalda Anselmo Vilela, Anna Carolina Soares Almeida, Márcia Maria Camargo de Morais
We describe colistin-resistant KPC-2-producing Klebsiella pneumoniae isolates from cerebrospinal fluid, belonging to ST423, selected during treatment for neuroinfection. Colistin resistance was related to mgrB gene interruption by an IS5-like.
February 2, 2018: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29530861/discovery-of-a-novel-metallo-%C3%AE-lactamase-inhibitor-that-potentiates-meropenem-activity-against-carbapenem-resistant-enterobacteriaceae
#12
Martin Everett, Nicolas Sprynski, Alicia Coelho, Jérôme Castandet, Maëlle Bayet, Juliette Bougnon, Clarisse Lozano, David T Davies, Simon Leiris, Magdalena Zalacain, Ian Morrissey, Sophie Magnet, Kirsty Holden, Peter Warn, Filomena De Luca, Jean-Denis Docquier, Marc Lemonnier
Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent and have become a major worldwide threat to human health. Carbapenem resistance is driven primarily by the acquisition of β-lactamase enzymes, which are able to degrade carbapenem antibiotics (hence termed carbapenemases) and result in high levels of resistance and treatment failure. Clinically relevant carbapenemases include both serine β-lactamases (SBLs; e.g., KPC-2 and OXA-48) and metallo-β-lactamases (MBLs), such as NDM-1...
May 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29507064/pneumonia-and-renal-replacement-therapy-are-risk-factors-for-ceftazidime-avibactam-treatment-failures-and-resistance-among-patients-with-carbapenem-resistant-enterobacteriaceae-infections
#13
Ryan K Shields, M Hong Nguyen, Liang Chen, Ellen G Press, Barry N Kreiswirth, Cornelius J Clancy
Ceftazidime-avibactam was used to treat 77 patients with carbapenem-resistant Enterobacteriaceae (CRE) infections at our center. Thirty- and 90-day survival rates were 81% and 69%, respectively; these rates were higher than those predicted by SAPS II and SOFA scores at the onset of infection. Clinical success was achieved for 55% of patients but differed by the site of infection. Success rates were lowest for pneumonia (36%) and higher for bacteremia (75%) and urinary tract infections (88%). By multivariate analysis, pneumonia ( P = 0...
May 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29506629/the-prevalence-of-cmy-2-oxa-48-and-kpc-2-genes-in-clinical-isolates-of-klebsiella-spp
#14
Talayeh Tavakoly, Samar Jamali, Ali Mojtahedi, Mohammadali Khan Mirzaei, Mohammad Shenagari
Klebsiella pneumoniae is a Gram-negative bacterium which causes several human infections. Treatment of infections related to K. pneumoniae has become problematic, because of increasing trend of extended spectrum β-lactamases producing (ESBLs) strains. The present study was aimed to detect the prevalence of ESBL-producing Klebsiella spp. and KPC-2, CMY-2 and OXA-48 β-lactamase encoding genes in clinical isolates of Klebsiella spp. isolated from hospitalized patients. In this cross-sectional study carried out from February to August 2014, 144 isolates of Klebsiella spp...
February 28, 2018: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29506074/morpholino-oligomers-tested-in-vitro-in-biofilm-and-in-vivo-against-multidrug-resistant-klebsiella-pneumoniae
#15
Bruce L Geller, Lixin Li, Fabian Martinez, Erin Sully, Carolyn R Sturge, Seth M Daly, Christine Pybus, David E Greenberg
Background: Klebsiella pneumoniae is an opportunistic pathogen and many strains are multidrug resistant. KPC is one of the most problematic resistance mechanisms, as it confers resistance to most β-lactams, including carbapenems. A promising platform technology for treating infections caused by MDR pathogens is the nucleic acid-like synthetic oligomers that silence bacterial gene expression by an antisense mechanism. Objectives: To test a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) in a mouse model of K...
March 1, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29499316/ceftazidime-avibactam-susceptibility-by-three-different-susceptibility-testing-methods-in-carbapenemase-producing-gram-negative-bacteria-from-australia
#16
Norelle L Sherry, Sarah L Baines, Benjamin P Howden
Avibactam is a novel β-lactamase inhibitor active against classes A, C and some class D β-lactamases. In combination with ceftazidime, it may be useful for the treatment of infections due to carbapenemase-producing Gram negative (CPGN) bacteria from these classes; however, susceptibility data for some of the less-common carbapenemases are limited. To assess the in vitro activity of ceftazidime-avibactam (CZA), we tested a panel of fifty diverse CPGN collected from clinical isolates in Victoria, Australia, containing KPC, GES, SME, OXA-23 and OXA-48-like carbapenemases for CZA susceptibility using broth microdilution (BMD), E-tests and disc diffusion...
February 27, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29488590/-kpc-klebsiella-pneumoniae-carbapenemase-main-carbapenemase-in-enterobacteriaceae
#17
Alejandra Vera-Leiva, Carla Barría-Loaiza, Sergio Carrasco-Anabalón, Celia Lima, Alejandro Aguayo-Reyes, Mariana Domínguez, Helia Bello-Toledo, Gerardo González-Rocha
The dissemination of carbapenemase-producing Enterobacteriaceae is currently considered a serious clinical problem due to the failure in the treatment of infections produced by them. Among the carbapenemases, the enzyme KPC has spread worldwide and has been identified in the main enterobacterial species related with healthcareassociated infections, although Klebsiella pneumoniae is the predominant specie. The blaKPC gene is transported, mainly by the transposon Tn4401, detected in various enterobacterial species of different sequence types (ST) and geographical origin...
October 2017: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
https://www.readbyqxmd.com/read/29486233/polymyxin-b-and-fosfomycin-thwart-kpc-producing-klebsiella-pneumoniae-in-the-hollow-fibre-infection-model
#18
Zackery P Bulman, Miao Zhao, Michael J Satlin, Liang Chen, Barry N Kreiswirth, Thomas J Walsh, Roger L Nation, Jian Li, Brian T Tsuji
Polymyxin B and fosfomycin are two 'old' antibiotics that consistently maintain activity against Klebsiella pneumoniae carbapenemase (KPC)-producing organisms based on in vitro susceptibility testing. However, each antibiotic's use in monotherapy has been associated with high rates of treatment failure. Therefore, our objective was to investigate the combinatorial pharmacodynamics of polymyxin B and fosfomycin against KPC-producing K. pneumoniae. Polymyxin B front-loading (3.33 mg/kg for 1 dose followed by 1...
February 24, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29483120/characteristics-of-carbapenemase-producing-enterobacteriaceae-in-wastewater-revealed-by-genomic-analysis
#19
Ryota Gomi, Tomonari Matsuda, Masaki Yamamoto, Pei-Hsin Chou, Michio Tanaka, Satoshi Ichiyama, Minoru Yoneda, Yasufumi Matsumura
Wastewater is considered a major source of antibiotic-resistant bacteria released into the environment. Here, we characterized carbapenemase-producing Enterobacteriaceae (CPE) in wastewater by whole-genome analysis. Wastewater samples ( n = 40) were collected from municipal wastewater treatment plants and hospital wastewater in Japan and Taiwan. Samples were screened for CPE using selective media, and the obtained isolates were sequenced using an Illumina MiSeq. The isolates ( n = 45) included the following microorganisms: Klebsiella quasipneumoniae ( n = 12), Escherichia coli ( n = 10), Enterobacter cloacae complex ( n = 10), Klebsiella pneumoniae ( n = 8), Klebsiella variicola ( n = 2), Raoultella ornithinolytica ( n = 1), Citrobacter freundii ( n = 1), and Citrobacter amalonaticus ( n = 1)...
May 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29444952/treatment-of-infections-caused-by-extended-spectrum-beta-lactamase-ampc-and-carbapenemase-producing-enterobacteriaceae
#20
REVIEW
Jesús Rodríguez-Baño, Belén Gutiérrez-Gutiérrez, Isabel Machuca, Alvaro Pascual
Therapy of invasive infections due to multidrug-resistant Enterobacteriaceae (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole...
April 2018: Clinical Microbiology Reviews
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