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https://www.readbyqxmd.com/read/29038270/activity-of-meropenem-vaborbactam-against-carbapenem-resistant-enterobacteriaceae-in-a-murine-model-of-pyelonephritis
#1
William J Weiss, Mark E Pulse, Phung Nguyen, Kelly Peterson, Jessica Silva, Jerry W Simecka, David Valtierra, Mojgan Sabet, David C Griffith
The recently approved combination of meropenem-vaborbactam (Vabomere™) is highly active against Gram-negative pathogens, especially KPC-producing, carbapenem-resistant Enterobacteriaceae We evaluated the efficacy of meropenem-vaborbactam against three clinically relevant isolates in a murine polynephritis model. Data indicated that the combination of meropenem-vaborbactam significantly increased the bacterial killing compared to the untreated controls. These data suggest that this combination may have utility in the treatment of complicated urinary tract infections due to KPC-producing, carbapenem-resistant Enterobacteriaceae...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29020404/colistin-vs-ceftazidime-avibactam-in-the-treatment-of-infections-due-to-carbapenem-resistant-enterobacteriaceae
#2
David van Duin, Judith J Lok, Michelle Earley, Eric Cober, Sandra S Richter, Federico Perez, Robert A Salata, Robert C Kalayjian, Richard R Watkins, Yohei Doi, Keith S Kaye, Vance G Fowler, David L Paterson, Robert A Bonomo, Scott Evans
Background: The efficacy of ceftazidime-avibactam - a cephalosporin-β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Enterobacteriaceae (CRE) - as compared to colistin remains unknown. Methods: Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on resistance against carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study...
September 4, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28951106/in-vitro-interaction-of-ceftazidime-avibactam-in-combination-with-different-antimicrobials-against-kpc-producing-klebsiella-pneumoniae-clinical-isolates
#3
Paolo Gaibani, Russell E Lewis, Silvia L Volpe, Maddalena Giannella, Caterina Campoli, Maria Paola Landini, PierLuigi Viale, Maria Carla Re, Simone Ambretti
OBJECTIVES: Combination therapy has been recommended when using ceftazidime-avibactam (CAZ-AVI) for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal combination is unknown. Six common antimicrobial agents (ertapenem, imipenem, meropenem, gentamicin, tigecycline, and ciprofloxacin) were evaluated for synergy with the recently approved cephalosporin-β-lactamase inhibitor combination CAZ-AVI in this study. METHODS: Different antimicrobial combinations were tested against 13 KPC-Kp, including CAZ-AVI-susceptible (n=11) and resistant (n=2) clinical isolates...
September 22, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28916900/were-all-carbapenemases-created-equal-treatment-of-ndm-producing-extensively-drug-resistant-enterobacteriaceae-a-case-report-and-literature-review
#4
REVIEW
Vindana Chibabhai, Trusha Nana, Norma Bosman, Teena Thomas, Warren Lowman
PURPOSE: There is currently a paucity of published literature focused on the treatment of infections caused by NDM-producing organisms. METHODS: We describe a case of a bacteraemia caused by an extensively drug-resistant (XDR) New Delhi metallo-β-lactamase (NDM)-producing Serratia marcescens and review the treatment options for XDR NDM-producing Enterobacteriaceae. RESULTS: Infections caused by New Delhi beta-lactamase (NDM)-producing Enterobacteriaceae are becoming increasingly prevalent worldwide...
September 15, 2017: Infection
https://www.readbyqxmd.com/read/28893690/new-agents-for-the-treatment-of-infections-with-gram-negative-bacteria-restoring-the-miracle-or-false-dawn
#5
REVIEW
H Wright, R A Bonomo, D L Paterson
BACKGROUND: Antibiotic resistance in Gram-negative resistance has developed without a commensurate response in the successful development of antibiotic agents, though recent progress has been made. AIMS: This review aims to provide a summary of the existing evidence on efficacy, spectrum of activity and the development of resistance of new agents that have been licensed or have completed advanced clinical trials and that possess activity against resistant Gram-negative organisms...
October 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28893689/management-of-kpc-producing-klebsiella-pneumoniae-infections
#6
REVIEW
M Bassetti, D R Giacobbe, H Giamarellou, C Viscoli, G L Daikos, G Dimopoulos, F G De Rosa, E J Giamarellos-Bourboulis, G M Rossolini, E Righi, I Karaiskos, M Tumbarello, D P Nicolau, P L Viale, G Poulakou
BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas. AIMS: our aim was to provide practical suggestion for physicians dealing with the management of KPC-KP infections in critically ill patients, based on expert opinions. SOURCES: PubMed search for relevant publications related to the management of KPC-KP infections. CONTENTS: a panel of experts developed a list of 12 questions to be addressed...
September 9, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28886559/sewage-treatment-effluents-in-delhi-a-key-contributor-of-%C3%AE-lactam-resistant-bacteria-and-genes-to-the-environment
#7
Manisha Lamba, Shaikh Ziauddin Ahammad
Rapid emergence of antibiotic resistance (AR) in developing countries is posing a greater health risk and increasing the global disease burden. Lack of access to safe drinking water, poor sanitation and inadequate sewage treatment facilities in these countries are fueling the problem associated with emergence of AR. Rapid proliferation of AR mediated by treated and untreated discharges from sewage treatment plants (STPs) is a prime public health concern. This study aims to understand the occurrence, fate, and routes of proliferation of carbapenem (KPC) and extended spectrum β-lactam (ESBL) resistant bacteria, and selected resistant genes in the samples collected from different unit operations in 12 STPs in New Delhi over two seasons...
August 28, 2017: Chemosphere
https://www.readbyqxmd.com/read/28841710/inhibition-of-rock1-kinase-modulates-both-tumor-cells-and-stromal-fibroblasts-in-pancreatic-cancer
#8
Clifford J Whatcott, Serina Ng, Michael T Barrett, Galen Hostetter, Daniel D Von Hoff, Haiyong Han
ROCK, or Rho-associated coiled coil-containing protein kinase, is a member of the AGC kinase family and has been shown to play a role in cell migration, ECM synthesis, stress-fiber assembly, and cell contraction. Increased ROCK expression has been reported in multiple pathological conditions, including cancer. Here, we report increased expression of ROCK 1 in pancreatic tumor epithelial cells as well as in cancer associated fibroblasts (CAF). In our analysis, 62% of tumor samples exhibited ≥2+ in staining intensity by IHC analysis, versus 40% of adjacent normal tissue samples (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/28840351/activity-of-temocillin-and-15-other-agents-including-fosfomycin-and-colistin-against-enterobacteriaceae-in-hong-kong
#9
Margaret Ip, Christopher K Lai, Kitty S C Fung, K-Tak Wong, Chendi Zhu, Sebastien Van de Velde, Dominic N Tsang, Peter Hawkey
Limited data are available on temocillin susceptibilities in Enterobacteriaceae from Asian countries where antimicrobial resistance is prevalent. The in vitro activities of temocillin and 15 commonly used antimicrobials against 613 non-duplicate blood (n = 310) and urine (with clinically significant bacteriuria; n = 303) isolates of Enterobacteriaceae from patients who attended 3 out of 7 clusters of public hospitals of the Hospital Authority, Hong Kong, during 2015/2016 were tested. Minimum inhibitory concentrations (MICs) were determined by Clinical and Laboratory Standards Institute (CLSI) microbroth dilution (agar dilution with fosfomycin)...
August 25, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28837596/membrane-active-macromolecules-kill-antibiotic-tolerant-bacteria-and-potentiate-antibiotics-towards-gram-negative-bacteria
#10
Divakara S S M Uppu, Mohini M Konai, Paramita Sarkar, Sandip Samaddar, Isabel C M Fensterseifer, Celio Farias-Junior, Paramanandam Krishnamoorthy, Bibek R Shome, Octávio L Franco, Jayanta Haldar
Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria...
2017: PloS One
https://www.readbyqxmd.com/read/28780361/untreated-urban-waste-contaminates-indian-river-sediments-with-resistance-genes-to-last-resort-antibiotics
#11
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...
November 1, 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
#12
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, 89Zr-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
#13
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
#14
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%C3%A2-pancreatic%C3%A2-carcinoma
#15
Yangchun Xie, Shan Zhu, Meizuo Zhong, Manhua Yang, Xiaofan Sun, Jinbao Liu, Guido Kroemer, Michael Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Induction of nonapoptotic 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-use-in-the-treatment-of-infections-due-to-kpc-producing-klebsiella-pneumoniae
#16
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 Klebsiella pneumoniae carbapenemase (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 a ≤10% to 15% likelihood of meropenem steady-state concentrations (Css) of >100 mg/liter...
October 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
#17
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
#18
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
#19
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
#20
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
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