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https://www.readbyqxmd.com/read/28510280/modelling-the-iatrogenic-pancreatic-cancer-risk-after-islet-autotransplantation-in-mouse
#1
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 equivalent islets (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 wild type 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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...
April 4, 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
#12
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
#13
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
https://www.readbyqxmd.com/read/28186976/32-phosphorus-selectively-delivered-by-listeria-to-pancreatic-cancer-demonstrates-a-strong-therapeutic-effect
#14
Dinesh Chandra, Benson Chellakkan Selvanesan, Ziqiang Yuan, Steven K Libutti, Wade Koba, Amanda Beck, Kun Zhu, Arturo Casadevall, Ekaterina Dadachova, Claudia Gravekamp
Our laboratory has developed a novel delivery platform using an attenuated non-toxic and non-pathogenic bacterium Listeria monocytogenes that infects tumor cells and selectively survives and multiplies in metastases and primary tumors with help of myeloid-derived suppressor cells (MDSC) and immune suppression in the tumor microenvironment (TME). 32P was efficiently incorporated into the Listeria bacteria by starvation of the bacteria in saline, and then cultured in phosphorus-free medium complemented with 32P as a nutrient...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28152085/a-putative-multi-replicon-plasmid-co-harboring-beta-lactamase-genes-blakpc-2-blactx-m-14-and-blatem-1-and-trimethoprim-resistance-gene-dfra25-from-a-klebsiella-pneumoniae-sequence-type-st-11-strain-in-china
#15
Yu Tang, Pinghua Shen, Wei Liang, Jialin Jin, Xiaofei Jiang
The global emergence of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae poses a major public health threat requiring immediate and aggressive action. Some older generation antibiotics, such as trimethoprim, serve as alternatives for treatment of infections. Here, we determined the complete nucleotide sequence of plasmid pHS091147, which co-harbored the carbapenemase (blaKPC-2) and trimethoprim resistance genes (dfrA25) from a Klebsiella pneumoniae sequence type (ST) 11 clone recovered in Shanghai, China...
2017: PloS One
https://www.readbyqxmd.com/read/28151407/rapid-detection-of-carbapenemases-in-enterobacteriaceae-evaluation-of-the-resist-3-o-k-n-oxa-48-kpc-ndm-lateral-flow-multiplexed-assay
#16
LETTER
David W Wareham, Muhd Haziq F Abdul Momin
No abstract text is available yet for this article.
April 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28102514/carbapenemase-producing-klebsiella-pneumoniae-bloodstream-infection-in-critically-ill-patients-risk-factors-and-predictors-of-mortality
#17
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/28089736/antibacterial-activity-of-limonium-brasiliense-baicuru-against-multidrug-resistant-bacteria-using-a-statistical-mixture-design
#18
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/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#19
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/28065546/discharge-of-kpc-2-genes-from-the-wwtps-contributed-to-their-enriched-abundance-in-the-receiving-river
#20
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
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