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https://www.readbyqxmd.com/read/28780361/untreated-urban-waste-contaminates-indian-river-sediments-with-resistance-genes-to-last-resort-antibiotics
#1
Nachiket P Marathe, Chandan Pal, Swapnil S Gaikwad, Viktor Jonsson, Erik Kristiansson, D G Joakim Larsson
Efficient sewage treatment is critical for limiting environmental transmission of antibiotic-resistant bacteria. In many low and middle income countries, however, large proportions of sewage are still released untreated into receiving water bodies. In-depth knowledge of how such discharges of untreated urban waste influences the environmental resistome is largely lacking. Here, we highlight the impact of uncontrolled discharge of partially treated and/or untreated wastewater on the structure of bacterial communities and resistome of sediments collected from Mutha river flowing through Pune city in India...
July 25, 2017: Water Research
https://www.readbyqxmd.com/read/28774899/89zr-anti-%C3%AE-h2ax-tat-but-not-18f-fdg-allows-early-monitoring-of-response-to-chemotherapy-in-a-mouse-model-of-pancreatic-ductal-adenocarcinoma
#2
James C Knight, Michael J Mosley, Luisa Contreras Bravo, Veerle Kersemans, Philip D Allen, Somnath Mukherjee, Eric O'Neill, Bart Cornelissen
Purpose: Late-stage, unresectable pancreatic ductal adenocarcinoma (PDAC) is largely resistant to chemotherapy and consequently has a very poor 5-year survival rate of < 5%. The ability to assess the efficacy of a treatment soon after its initiation would enable rapid switching to potentially more effective therapies if the current treatment is found to be futile. We have evaluated the ability of the PET imaging agent, (89)Zr-anti-γH2AX-TAT, to monitor DNA damage in response to fluouracil (5-FU), gemcitabine, or capecitabine treatment in a mouse model of pancreatic cancer...
August 3, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28767588/successful-ceftazidime-avibactam-treatment-of-mdr-kpc-positive-klebsiella-pneumoniae-infection-in-a-patient-with-traumatic-brain-injury-a-case-report
#3
Agnese Gugliandolo, Carla Caio, Maria Lina Mezzatesta, Carmela Rifici, Placido Bramanti, Stefania Stefani, Emanuela Mazzon
RATIONALE: Carbapenem-resistant Enterobacteriaceae infections are a serious health care problem, because of the high mortality. Carbapenem resistance is mainly caused by carbapenemases production, including Klebsiella pneumoniae carbapenemase (KPC). Ceftazidime-avibactam is a new cephalosporin/β-lactamase inhibitor combination for the treatment of complicated urinary, intra-abdominal infections, and nosocomial pneumonia caused by gram negative, or other serious gram-negative infections...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28765154/gemcitabine-induced-timp1-attenuates-therapy-response-and-promotes-tumor-growth-and-liver-metastasis-in-pancreatic-cancer
#4
Zenobia D'Costa, Keaton Jones, Abul Azad, Ruud van Stiphout, Su Y Lim, Ana L Gomes, Paul Kinchesh, Sean C Smart, W Gillies McKenna, Francesca M Buffa, Owen J Sansom, Ruth J Muschel, Eric O'Neill, Emmanouil Fokas
Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to this agent. Molecular markers downstream of gemcitabine treatment in pre-clinical models may provide an insight into resistance mechanisms. Using cytokine arrays, we identified potential secretory biomarkers of gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC. We verified the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using both in vitro techniques and animal models...
August 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28764929/inhibition-of-aurora-kinase-a-induces-necroptosis-in-pancreatic-carcinoma
#5
Yangchun Xie, Shan Zhu, Meizuo Zhong, Minghua Yang, Xiaofan Sun, Jinbao Liu, Guido Kroemer, Michael Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Induction of non-apoptotic cell death could be an approach to eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). METHODS: We screened 273 commercially available kinase inhibitors for cytotoxicity against a human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2...
July 29, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28760900/population-pharmacokinetics-of-high-dose-continuous-infusion-meropenem-and-considerations-for-the-use-in-the-treatment-of-infections-due-to-kpc-producing-klebsiella-pneumoniae
#6
Piergiorgio Cojutti, Assunta Sartor, Elda Righi, Claudio Scarparo, Matteo Bassetti, Federico Pea
We assessed the population pharmacokinetics of high-dose continuous infusion (HDCI) meropenem in a cohort of patients with KPC-producing Klebsiella pneumoniae (KPC-Kp) infections. Monte Carlo simulations were used to define the permissible HDCI meropenem regimens that could be safely considered for the treatment of KPC-Kp infections due to meropenem-resistant strains. Permissible doses were arbitrarily defined as those associated with ≤10-15% likelihood of meropenem steady-state concentrations (Css) >100 mg/L...
July 31, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28756598/risk-factors-and-predictors-of-mortality-of-candidaemia-among-critically-ill-patients-role-of-antifungal-prophylaxis-in-its-development-and-in-selection-of-non-albicans-species
#7
Matthaios Papadimitriou-Olivgeris, Anastasia Spiliopoulou, Fotini Fligou, Iris Spiliopoulou, Lora Tanaseskou, Georgios Karpetas, Markos Marangos, Evangelos D Anastassiou, Myrto Christofidou
PURPOSE: The aim of the present study is to identify risk factors for development and predictors of mortality of candidaemia among critically ill patients. METHODS: A 1:7 case-control study was conducted during a 4-year period (2012-2015) in a Greek Intensive Care Unit (ICU). Candidaemia was confirmed by positive blood cultures. All yeasts were identified using API 20C AUX System or Vitek 2 Advanced Expert System. Epidemiologic data were collected from the ICU computerized database and patients' chart reviews...
July 29, 2017: Infection
https://www.readbyqxmd.com/read/28738823/metformin-suppresses-cancer-initiation-and-progression-in-genetic-mouse-models-of-pancreatic-cancer
#8
Ke Chen, Weikun Qian, Zhengdong Jiang, Liang Cheng, Jie Li, Liankang Sun, Cancan Zhou, Luping Gao, Meng Lei, Bin Yan, Junyu Cao, Wanxing Duan, Qingyong Ma
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-associated mortality worldwide with an overall five-year survival rate less than 7%. Accumulating evidence has revealed the cancer preventive and therapeutic effects of metformin, one of the most widely prescribed medications for type 2 diabetes mellitus. However, its role in pancreatic cancer is not fully elucidated. Herein, we aimed to further study the preventive and therapeutic effects of metformin in genetically engineered mouse models of pancreatic cancer...
July 24, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28715967/hyperthermia-enhanced-targeted-drug-delivery-using-magnetic-resonance-guided-focussed-ultrasound-a-pre-clinical-study-in-a-genetic-model-of-pancreatic-cancer
#9
Navid Farr, Yak-Nam Wang, Samantha D'Andrea, Frank Starr, Ari Partanen, Kayla M Gravelle, Jeannine S McCune, Linda J Risler, Stella G Whang, Amy Chang, Sunil R Hingorani, Donghoon Lee, Joo Ha Hwang
PURPOSE: The lack of effective treatment options for pancreatic cancer has led to a 5-year survival rate of just 8%. Here, we evaluate the ability to enhance targeted drug delivery using mild hyperthermia in combination with the systemic administration of a low-temperature sensitive liposomal formulation of doxorubicin (LTSL-Dox) using a relevant model for pancreas cancer. MATERIALS AND METHODS: Experiments were performed in a genetically engineered mouse model of pancreatic cancer (KPC mice: LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre)...
July 17, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28700049/molecular-detection-of-%C3%AE-lactamase-and-integron-genes-in-clinical-strains-of-klebsiella-pneumoniae-by-multiplex-polymerase-chain-reaction
#10
Mansour Sedighi, Masoumeh Halajzadeh, Rashid Ramazanzadeh, Noor Amirmozafari, Mohsen Heidary, Serve Pirouzi
INTRODUCTION: Infections caused by β-lactamase-producing gram-negative bacteria, such as Klebsiella pneumoniae, are increasing globally with high morbidity and mortality. The aim of the current study was to determine antimicrobial susceptibility patterns and the prevalence of antibiotic resistance genes (β-lactamase and integron genes) using multiplex PCR. METHODS: One-hundred K. pneumoniae isolates were collected from different clinical samples. Antibiotic susceptibility testing was performed with thirteen different antibiotics...
May 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28668692/wastewater-is-a-reservoir-for-clinically-relevant-carbapenemase-and-16s-rrna-methylase-producing-enterobacteriaceae
#11
Katrin Zurfluh, Claudia Bagutti, Peter Brodmann, Monica Alt, Jürg Schulze, Séamus Fanning, Roger Stephan, Magdalena Nüesch-Inderbinen
The aim of the study was to evaluate wastewater for carbapenemase producing Enterobacteriaceae (CPE) and 16S rRNA methylase producing Gram negative bacteria (MPB), and to assess their occurrence following wastewater treatment. Wastewater samples were collected between June 2015 and March 2016 in the sewage network of the city of Basel from sites located before and after influx of wastewater from the hospital into the sewage network. Samples were also obtained from the influent and from the effluent of the receiving wastewater treatment plant...
June 28, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28659886/molecular-epidemiology-and-risk-factors-of-carbapenem-resistant-klebsiella-pneumoniae-infections-in-eastern-china
#12
Bing Zheng, Yingxin Dai, Yang Liu, Weiyang Shi, Erkuan Dai, Yichao Han, Dandan Zheng, Yuetian Yu, Min Li
Background: The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses an immediate threat to treatment worldwide. This retrospective study assessed the molecular epidemiology and determined the risk factors for and outcomes of CRKP infections in a general teaching hospital in Shanghai, China. Methods: From January 2013 to July 2015, 100 consecutive unique CRKP isolates isolated from hospitalized patients were collected. Isolates were screened for antibiotic resistance genes by polymerase chain reaction and molecular typing was performed by pulsed-field gel electrophoresis (PFGE)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28650688/multidrug-resistant-enterobacteriaceae-in-lebanese-hospital-wastewater-implication-in-the-one-health-concept
#13
Ziad Daoud, Jina Farah, Elie Salem Sokhn, Khalil El Kfoury, Elias Dahdouh, Khalil Masri, Claude Afif, Roula M Abdel-Massih, Ghassan M Matar
Extended-spectrum beta-lactamases (ESBL) and carbapenemase-producing organisms pose severe problems for hospitalized patients. In the absence of efficient sanitation and sewage disposal, the risks for transmission of hospital organisms into the community are high. Our objectives were to study the occurrence and mechanisms of resistance of multidrug-resistant gram-negative bacilli in two Lebanese hospital sewage treatment plants. Wastewater samples were collected, filtered, and cultivated on MacConckey+cefotaxime agars...
June 26, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28637339/emergence-of-ceftazidime-avibactam-non-susceptibility-in-an-mdr-klebsiella-pneumoniae-isolate
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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 versus 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% produced K...
August 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
#20
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
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 when the isolates show a meropenem or imipenem MIC of <16 mg/liter. However, the optimal treatment of BSI caused by colistin- and high-level carbapenem-resistant KPC-producing K. pneumoniae is unknown. A prospective cohort study including episodes of bacteremia caused by colistin-resistant and high-level meropenem-resistant (MIC ≥ 64 mg/liter) KPC-producing K...
August 2017: Antimicrobial Agents and Chemotherapy
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