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https://www.readbyqxmd.com/read/28637339/emergence-of-ceftazidime-avibactam-non-susceptibility-in-an-mdr-klebsiella-pneumoniae-isolate
#1
Anna Both, Henning Büttner, Jiabin Huang, Markus Perbandt, Cristina Belmar Campos, Martin Christner, Florian P Maurer, Stefan Kluge, Christina König, Martin Aepfelbacher, Dominic Wichmann, Holger Rohde
Background: Avibactam is a novel broad-range β-lactamase inhibitor active against Ambler class A (including ESBL and KPC) and some Ambler class C and D (e.g. OXA-48) enzymes. We here report on the emergence of ceftazidime/avibactam resistance in clinical, multiresistant, OXA-48 and CTX-M-14-producing Klebsiella pneumoniae isolate DT12 during ceftazidime/avibactam treatment. Methods and results: Comparative whole-genome sequence analysis identified two SNPs in the CTX-M-14-encoding gene leading to two amino acid changes (P170S and T264I)...
June 16, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28614760/abundance-of-carbapenemase-genes-blakpc-blandm-and-blaoxa-48-in-wastewater-effluents-from-tunisian-hospitals
#2
Emna Nasri, Jessica Subirats, Alexandre Sànchez-Melsió, Hedi Ben Mansour, Carles M Borrego, José Luis Balcázar
Carbapenems are β-lactam antibiotics with a broad spectrum of activity and are usually considered the last resort for the treatment of severe infections caused by multidrug-resistant pathogens. The clinically most significant carbapenemases are KPC, NDM, and OXA-48-like enzymes, whose genes have been increasingly reported worldwide in members of the family Enterobacteriaceae. In this study, we quantified the abundance of these genes in wastewater effluents from different Tunisian hospitals. The blaNDM and blaOXA-48-like genes were detected at similar concentrations in all hospital wastewater effluents...
June 11, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28611107/il-6-receptor-blockade-enhances-chemotherapy-efficacy-in-pancreatic-ductal-adenocarcinoma
#3
Kristen B Long, Graham Tooker, Evan Tooker, Santiago Lombo Luque, Jae W Lee, Xiaoqing Pan, Gregory L Beatty
Inflammation mediated by activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling is a major cause of chemotherapy resistance in cancer. We studied the impact of selectively blocking the IL-6 receptor (IL6R) as a strategy to inhibit IL-6-induced STAT activation and to overcome chemoresistance in pancreatic ductal adenocarcinoma (PDAC). To do this, STAT activation was investigated in tumors arising spontaneously in LSL-Kras(G12D/+);LSL-Trp53(R172H/+);Pdx-1Cre (KPC) mice...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28589468/optimal-treatment-of-jugular-foramen-schwannomas-long-term-outcome-of-a-multidisciplinary-approach-for-a-series-of-29-cases-in-a-single-institute
#4
Sung Mo Ryu, Jung-Il Lee, Kwan Park, Jung Won Choi, Doo-Sik Kong, Do-Hyun Nam, Han-Shin Jeong, Yang-Sun Cho, Ho Jun Seol
BACKGROUND: The goal of treatment for jugular foramen schwannomas (JFSs) is to achieve complete tumor removal with cranial nerve preservation. However, achieving this goal remains a challenge despite the advances in microsurgical techniques. The aim of this study was to determine optimal treatment strategies for JFSs based on a review of a series of 29 surgical cases in our institute. MATERIALS AND METHODS: Between 1997 and 2013, 29 patients with JFSs underwent surgical treatment by multidisciplinary otoneurosurgical approaches...
June 6, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28572684/%C3%AF-bo1e-a-newly-discovered-lytic-bacteriophage-targeting-carbapenemase-producing-klebsiella-pneumoniae-of-the-pandemic-clonal-group-258-clade-ii-lineage
#5
Marco Maria D'Andrea, Pasquale Marmo, Lucia Henrici De Angelis, Mattia Palmieri, Nagaia Ciacci, Gustavo Di Lallo, Elisa Demattè, Elisa Vannuccini, Pietro Lupetti, Gian Maria Rossolini, Maria Cristina Thaller
The pandemic dissemination of KPC carbapenemase-producing Klebsiella pneumoniae (KPC-KP) represents a major public health problem, given their extensive multidrug resistance profiles and primary role in causing healthcare-associated infections. This phenomenon has largely been contributed by strains of Clonal Group (CG) 258, mostly of clade II, which in some areas represent the majority of KPC-KP isolates. Here we have characterized a newly discovered lytic Podoviridae, named φBO1E, targeting KPC-KP strains of clade II lineage of CG258...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28559250/ceftazidime-avibactam-is-superior-to-other-treatment-regimens-against-carbapenem-resistant-klebsiella-pneumoniae-bacteremia
#6
Ryan K Shields, M Hong Nguyen, Liang Chen, Ellen G Press, Brian A Potoski, Rachel V Marini, Yohei Doi, Barry N Kreiswirth, Cornelius J Clancy
There are no data comparing outcomes of patients treated with ceftazidime-avibactam vs. comparators for carbapenem-resistant Enterobacteriaceae infections. At our center, ceftazidime-avibactam treatment of carbapenem-resistant Klebsiella pneumoniae bacteremia was associated with higher rates of clinical success (P=0.006) and survival (P=0.01) than other regimens. Across treatment groups, there were no differences in underlying diseases, severity of illness, source of bacteremia, or strain characteristics (97% were KPC-producing)...
May 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28559247/mortality-associated-with-bacteremia-due-to-colistin-resistant-klebsiella-pneumoniae-with-high-level-meropenem-resistance-importance-of-combination-therapy-without-colistin-and-carbapenems
#7
Isabel Machuca, Belén Gutiérrez-Gutiérrez, Irene Gracia-Ahufinger, Francisco Rivera Espinar, Ángela Cano, Julia Guzmán-Puche, Elena Pérez-Nadales, Clara Natera, Marina Rodríguez, Rafael León, Juan J Castón, Fernando Rodríguez-López, Jesús Rodríguez-Baño, Julián Torre-Cisneros
Background. Combination therapy including colistin and a carbapenem has been found to be associated with lower mortality in the treatment of bloodstream infections (BSI) due to KPC-producing Klebsiella pneumoniae (KPCKP) when the isolates show a meropenem or imipenem MIC < 16 mg/L. However, the optimal treatment of BSI caused by colistin and high level carbapenem-resistant KPCKP is unknown. Methods.A prospective cohort study including episodes of bacteremia caused by colistin-resistant and high-level meropenem-resistant (MIC ≥ 64 mg/L) KPCKP diagnosed from July 2012 to February 2016 was performed...
May 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28510280/modeling-the-iatrogenic-pancreatic-cancer-risk-after-islet-autotransplantation-in-mouse
#8
E Dugnani, V Pasquale, D Liberati, A Citro, E Cantarelli, S Pellegrini, P Marra, T Canu, G Balzano, M Scavini, A Esposito, C Doglioni, L Piemonti
Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk of islet autotransplantation performed after pancreatectomy. To model this risk, islets and/or pancreatic exocrine clusters obtained from a genetically engineered mouse model for pancreatic ductal adenocarcinoma (the LSL-Kras(G12D/+) ;LSL-Trp53(R172H/+) ;Pdx-1-Cre, termed KPC mouse) were transplanted via the portal vein in syngeneic wild type (WT) severely diabetic recipients in the following treatment groups: group A (n = 11) received KPC exocrine clusters in volume equal to 250 islet equivalents (IEQs); group B (n = 12) received 250 WT IEQs mixed with KPC exocrine clusters (1:1 volume ratio); group C (n = 5) received 250 KPC IEQs, and group D (n = 7) received 250 WT IEQs...
May 16, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28507112/mcr-1-and-oxa-48-in-vivo-acquisition-in-kpc-producing-escherichia-coli-after-colistin-treatment
#9
Racha Beyrouthy, Frederic Robin, Aude Lessene, Igor Lacombat, Laurent Dortet, Thierry Naas, Valérie Ponties, Richard Bonnet
The spread of mcr-1-encoding plasmids into carbapenem-resistant Enterobacteriaceae raises concerns about the emergence of untreatable bacteria. We report the acquisition of mcr-1 in a carbapenem- resistant E. coli after a 3-week course of colistin in a patient repatriated to France from Portugal. Whole-genome sequencing revealed that the KPC-producing E. coli strain acquired two plasmids, an IncL OXA-48-encoding plasmid and an IncX4 mcr-1-encoding plasmid. This is the first report of mcr-1 in carbapenemase-encoding bacteria in France...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28498440/gastrin-induces-multidrug-resistance-via-the-degradation-of-p27kip1-in-the-gastric-carcinoma-cell-line-sgc7901
#10
Kun Zhuang, Lingxia Zhang, Xin Zhang, Hailing Tang, Jun Zhang, Yuan Yan, Kun Han, Hanqing Guo
Multidrug resistance (MDR) is one of the major reasons for the failure of chemotherapy-based gastric carcinoma (GC) treatments, hence, biologically based therapies are urgently needed. Gastrin (GAS), a key gastrointestinal (GI) hormone, was found to be involved in tumor formation, progression, and metastasis. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining analysis revealed a high level of expression of GAS in drug-insensitive GC tissues (P<0.01) and similar results were revealed in GC cell lines SGC7901 and its multidrug-resistant variants SGC7901/VCR and SGC7901/ADR...
May 4, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28461318/impaired-inhibition-by-avibactam-and-resistance-to-the-ceftazidime-avibactam-combination-due-to-the-d-179-y-substitution-in-the-%C3%AE-lactamase-kpc-2
#11
Fabrice Compain, Michel Arthur
The ceftazidime-avibactam combination was recently shown to be at risk of emergence of resistance under treatment. To gain insight into the underlying mechanism, we have analyzed the catalytic properties of a KPC-2 β-lactamase harboring the D(179)Y substitution. We show that impaired inhibition by avibactam combined with significant residual activity for ceftazidime hydrolysis accounts for resistance. In contrast, the D(179)Y substitution abolished hydrolysis of aztreonam and imipenem indicating these drugs might provide therapeutic alternatives...
May 1, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28457352/carbapenem-resistant-enterobacteriaceae
#12
REVIEW
Alina Iovleva, Yohei Doi
Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a major threat. Commonly used antibiotics are generally inactive against CRE. Therefore, timely detection of CRE is of paramount importance. Among CRE, those producing carbapenem-hydrolyzing β-lactamase enzymes (carbapenemase-producing Enterobacteriaceae) are particularly of concern because they tend to spread, and treatment is difficult. The carbapenemase groups most commonly encountered include KPC, NDM, and OXA-48. Treatment options are limited and include combinations of polymyxins, tigecycline, aminoglycosides, or carbapenems; newer agents with activity against CRE and better safety profiles are becoming available and will likely emerge as the preferred therapy...
June 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/28453537/an-efficient-and-robust-mri-guided-radiotherapy-planning-approach-for-targeting-abdominal-organs-and-tumours-in-the-mouse
#13
Veerle Kersemans, John S Beech, Stuart Gilchrist, Paul Kinchesh, Philip D Allen, James Thompson, Ana L Gomes, Zenobia D'Costa, Luke Bird, Iain D C Tullis, Robert G Newman, Aurelien Corroyer-Dulmont, Nadia Falzone, Abul Azad, Katherine A Vallis, Owen J Sansom, Ruth J Muschel, Borivoj Vojnovic, Mark A Hill, Emmanouil Fokas, Sean C Smart
INTRODUCTION: Preclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse. METHODS: A multimodality cradle was developed for providing subject immobilisation and its performance was evaluated. Whilst CT was still used for dose calculations, target identification was based on MRI...
2017: PloS One
https://www.readbyqxmd.com/read/28449953/detection-of-colonization-by-carbapenem-resistant-organisms-by-real-time-polymerase-chain-reaction-from-rectal-swabs-in-patients-with-chronic-renal-disease
#14
T F T Rezende, A M Doi, M G Quiles, A C C Pignatari, S Manfrendi, C Grothe, M Taminato, D A Barbosa
BACKGROUND: Carbapenem-resistant organism (CRO) colonization is a serious problem that increases the risk of infection and contributes to dissemination of antimicrobial resistance in healthcare-associated environments. The risk of acquisition and dissemination of CRO is high in chronic renal failure patients and the surveillance culture is recommended as a component of infection control programmes. AIM: To assess colonization by CRO, comparing phenotypic and molecular-based methods of diagnostics, in rectal swabs in a large population of chronic renal failure patients...
March 24, 2017: Journal of Hospital Infection
https://www.readbyqxmd.com/read/28444620/environmental-pollution-with-antimicrobial-agents-from-bulk-drug-manufacturing-industries-in-hyderabad-south-india-is-associated-with-dissemination-of-extended-spectrum-beta-lactamase-and-carbapenemase-producing-pathogens
#15
Christoph Lübbert, Christian Baars, Anil Dayakar, Norman Lippmann, Arne C Rodloff, Martina Kinzig, Fritz Sörgel
PURPOSE: High antibiotic and antifungal concentrations in wastewater from anti-infective drug production may exert selection pressure for multidrug-resistant (MDR) pathogens. We investigated the environmental presence of active pharmaceutical ingredients and their association with MDR Gram-negative bacteria in Hyderabad, South India, a major production area for the global bulk drug market. METHODS: From Nov 19 to 28, 2016, water samples were collected from the direct environment of bulk drug manufacturing facilities, the vicinity of two sewage treatment plants, the Musi River, and habitats in Hyderabad and nearby villages...
April 26, 2017: Infection
https://www.readbyqxmd.com/read/28444224/pharmacodynamics-of-colistin-and-fosfomycin-a-treasure-trove-combination-combats-kpc-producing-klebsiella-pneumoniae
#16
Miao Zhao, Zackery P Bulman, Justin R Lenhard, Michael J Satlin, Barry N Kreiswirth, Thomas J Walsh, Amanda Marrocco, Phillip J Bergen, Roger L Nation, Jian Li, Jing Zhang, Brian T Tsuji
Objectives: KPC-producing Klebsiella pneumoniae are an emerging public health problem around the globe. We defined the combinatorial pharmacodynamics and ability to suppress resistance of two 'old' antibiotics, fosfomycin and colistin, in time-kill experiments and hollow-fibre infection models (HFIM). Methods: Two KPC-2-producing K. pneumoniae isolates were used: one susceptible to both colistin and fosfomycin (KPC 9A: MIC colistin 0.25 mg/L and MIC fosfomycin ≤8 mg/L) and the other resistant to colistin and susceptible to fosfomycin (KPC 5A: MIC colistin 64 mg/L and MIC fosfomycin 32 mg/L)...
April 21, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28438930/in-vitro-assessment-of-combined-polymyxin-b-and-minocycline-therapy-against-klebsiella-pneumoniae-carbapenemase-kpc-producing-k-pneumoniae
#17
Dennis Huang, Brenda Yu, John K Diep, Rajnikant Sharma, Michael Dudley, Keith S Kaye, Jason M Pogue, Cely Abboud Saad, Gauri Rao
The multi-drug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes have been reported with intravenous minocycline-based combination treatments for infections caused by carbapenemase-producing bacteria. The objective of this study was to evaluate the in vitro activity of polymyxin B and minocycline combination therapy against six KPC-2-producing K...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28389354/treating-complicated-carbapenem-resistant-enterobacteriaceae-infections-with-ceftazidime-avibactam-a-retrospective-study-with-molecular-strain-characterisation
#18
Fiorella Krapp, Jennifer L Grant, Sarah H Sutton, Egon A Ozer, Viktorija O Barr
Ceftazidime/avibactam (CAZ/AVI) is the first antimicrobial agent with activity against carbapenem-resistant Enterobacteriaceae (CRE) approved by the US Food and Drug Administration (FDA). Notably, human clinical outcome data for this indication are limited. Therefore, a retrospective study was performed to evaluate the clinical outcomes and bacterial genomic characteristics of patients hospitalised at a tertiary medical centre with CRE infections treated for the first time with CAZ/AVI. From a total of 44 patients with CRE infections, 6 patients were treated with CAZ/AVI...
June 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28333332/wck-5222-cefepime-zidebactam-antimicrobial-activity-tested-against-gram-negative-organisms-producing-clinically-relevant-%C3%AE-lactamases
#19
Helio S Sader, Paul R Rhomberg, Robert K Flamm, Ronald N Jones, Mariana Castanheira
Background: Zidebactam is a β-lactam enhancer antibiotic with a dual mechanism of action involving binding to Gram-negative PBP2 and β-lactamase inhibition. Cefepime combined with zidebactam (WCK 5222) is under clinical development for treatment of Gram-negative infections. Objectives: To evaluate the in vitro activities of cefepime and zidebactam separately and combined at 1:1 and 2:1 ratios when tested against Gram-negative organisms producing the most clinically relevant β-lactamase types...
June 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28242667/in-vitro-selection-of-meropenem-resistance-among-ceftazidime-avibactam-resistant-meropenem-susceptible-klebsiella-pneumoniae-isolates-with-variant-kpc-3-carbapenemases
#20
Ryan K Shields, M Hong Nguyen, Ellen G Press, Liang Chen, Barry N Kreiswirth, Cornelius J Clancy
Ceftazidime-avibactam resistance is mediated by blaKPC-3 mutations, which restore carbapenem susceptibility. We subjected Klebsiella pneumoniae isolates with different blaKPC-3 mutations (n = 5) or wild-type blaKPC-3 (n = 2) to serial passages with meropenem. The meropenem MIC against each isolate increased. Mutations in the ompK36 porin gene evolved in 5 isolates. Among isolates with D179Y substitutions in KPC-3, blaKPC-3 mutations reverted to wild type, were replaced by new mutations, or were retained. Carbapenem treatment of ceftazidime-avibactam-resistant K...
May 2017: Antimicrobial Agents and Chemotherapy
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