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https://www.readbyqxmd.com/read/28935481/stalking-a-lethal-superbug-by-whole-genome-sequencing-and-phylogenetics-influence-on-unraveling-a-major-hospital-outbreak-of-carbapenem-resistant-klebsiella-pneumoniae
#1
Thorsten Kaiser, Knut Finstermeier, Madlen Häntzsch, Sarah Faucheux, Martin Kaase, Tim Eckmanns, Sven Bercker, Udo X Kaisers, Norman Lippmann, Arne C Rodloff, Joachim Thiery, Christoph Lübbert
BACKGROUND: From July 2010-April 2013, Leipzig University Hospital experienced the largest outbreak of a Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing Klebsiella pneumoniae (KPC-2-Kp) strain observed in Germany to date. After termination of the outbreak, we aimed to reconstruct transmission pathways by phylogenetics based on whole-genome sequencing (WGS). METHODS: One hundred seventeen KPC-2-Kp isolates from 89 outbreak patients, 5 environmental KPC-2-Kp isolates, and 24 K pneumoniae strains not linked to the outbreak underwent WGS...
September 18, 2017: American Journal of Infection Control
https://www.readbyqxmd.com/read/28934293/generation-of-a-pancreatic-cancer-model-using-a-pdx1-flp-recombinase-knock-in-allele
#2
Jinghai Wu, Xin Liu, Sunayana G Nayak, Jason R Pitarresi, Maria C Cuitiño, Lianbo Yu, Blake E Hildreth, Katie A Thies, Daniel J Schilling, Soledad A Fernandez, Gustavo Leone, Michael C Ostrowski
The contribution of the tumor microenvironment to the development of pancreatic adenocarcinoma (PDAC) is unclear. The LSL-KrasG12D/+;LSL-p53R172H/+;Pdx-1-Cre (KPC) tumor model, which is widely utilized to faithfully recapitulate human pancreatic cancer, depends on Cre-mediated recombination in the epithelial lineage to drive tumorigenesis. Therefore, specific Cre-loxP recombination in stromal cells cannot be applied in this model, limiting the in vivo investigation of stromal genetics in tumor initiation and progression...
2017: PloS One
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
#3
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
#4
REVIEW
Hugh Wright, Robert A Bonomo, David 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 completed advanced clinical trials that possess activity against resistant gram-negative organisms...
September 8, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28893689/management-of-kpc-producing-klebsiella-pneumoniae-infections
#5
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/28888401/detection-of-carbapenemases-and-other-mechanisms-of-enzymatic-resistance-to-%C3%AE-lactams-in-enterobacteriaceae-with-diminished-susceptibility-to-carbapenems-in-a-tertiary-care-hospital
#6
Marta María Gómara-Lomero, Ana Isabel López-Calleja, Berta María Pilar Vela Iglesia, Isabel Ferrer Cerón, Antonio Rezusta López, María José Revillo Pinilla
INTRODUCTION: Our objective was to characterize the enzymatic β-lactam resistance in clinical Enterobacteriaceae isolates with diminished susceptibility to carbapenems from 2013 to 2014 at Hospital Universitario Miguel Servet. MATERIAL/METHODS: A total of 63 clinical isolates were analyzed for the presence of carbapenemases (KPC, OXA-48 and MBL), ESBLs and AmpC enzymes by combined disk methods and PCR detection of carbapenemase-encoding and beta-lactamase-encoding genes...
September 6, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/28887199/temporal-evolution-of-polymyxin-b-resistant-klebsiella-pneumoniae-clones-recovered-from-blood-cultures-in-a-teaching-hospital-during-a-7-year-period
#7
Graziela Braun, Rodrigo Cayô, Adriana Pereira Matos, Juliane de Mello Fonseca, Ana Cristina Gales
The polymyxins have become one of the last resorts to treat serious infections caused by KPC-2-producing Klebsiella pneumoniae worldwide. However, the increase of polymyxin consumption has favored the emergence of resistance to these compounds. In this study we observed an increase in the polymyxin B resistance rates from 0 to 30.6% among 224 K. pneumoniae isolates recovered from blood cultures between 2009 and 2015. Only gentamicin, tigecycline and fosfomycin remained active against the polymyxin B-resistant K...
September 5, 2017: International Journal of Antimicrobial Agents
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
#8
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/28874377/high-level-resistance-to-colistin-mediated-by-various-mutations-in-the-crrb-gene-among-carbapenemase-producing-klebsiella-pneumoniae
#9
Aurélie Jayol, Patrice Nordmann, Adrian Brink, Maria-Virginia Villegas, Véronique Dubois, Laurent Poirel
Mutations in the crrAB genes encoding a two-component regulator involved in modifications of the lipopolysaccharide were searched for among a collection of colistin-resistant Klebsiella pneumoniae isolates. Four isolates respectively producing carbapenemases NDM-1, OXA-181, or KPC-2 showed mutated CrrB proteins compared to wild-type strains. Complementation assays with a wild-type CrrB protein restored the susceptibility to colistin in all cases, confirming the involvement of the identified substitutions in the resistance phenotype...
September 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28856222/comparison-of-clinical-methods-for-detecting-carbapenem-resistant-enterobacteriaceae
#10
Kirsten Kost, Jumi Yi, Beverly Rogers, Robert Jerris
We evaluated detection of carbapenem-resistant Enterobacteriaceae (CRE) by routine minimal inhibitory concentration (MIC) testing, polymerase chain reaction (PCR) using Xpert® Carba-R assay, hydrolysis of ertapenem and imipenem detected by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), and hydrolysis by colorimetry using the EPI-CRE assay. Ninety-six Enterobacteriaceae isolates possessing carbapenemase genes and 29 carbapenem-susceptible Enterobacteriaceae were available for testing...
August 2017: Pract Lab Med
https://www.readbyqxmd.com/read/28846083/glia-initiate-brain-assembly-through-noncanonical-chimaerin-furin-axon-guidance-in-c-elegans
#11
Georgia Rapti, Chang Li, Alan Shan, Yun Lu, Shai Shaham
Brain assembly is hypothesized to begin when pioneer axons extend over non-neuronal cells, forming tracts guiding follower axons. Yet pioneer-neuron identities, their guidance substrates, and their interactions are not well understood. Here, using time-lapse embryonic imaging, genetics, protein-interaction, and functional studies, we uncover the early events of C. elegans brain assembly. We demonstrate that C. elegans glia are key for assembly initiation, guiding pioneer and follower axons using distinct signals...
August 28, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28844719/evaluation-of-a-rapid-immunochromatographic-test-for-detection-of-distinct-variants-of-klebsiella-pneumoniae-carbapenemase-kpc-in-enterobacteriaceae
#12
Ana C Ramos, Ana C Gales, Jussimara Monteiro, Suzane Silbert, Thomás Chagas-Neto, Antonia M O Machado, Cecilia G Carvalhaes
The rapid detection of KPC-producing Enterobacteriaceae by microbiology laboratories has been required for infectious control programs. Herein we evaluated the performance of a novel immunochromatographic test for detecting KPC-2-, KPC-3-, KPC-4-, KPC-6-, KPC-7-, KPC-8-, and KPC-11-producing isolates and the influence of different growth media on the test performance.
August 24, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28844390/photodynamic-inactivation-of-multiresistant-bacteria-kpc-using-zinc-ii-phthalocyanines
#13
Mariana Miretti, Romina Clementi, Tomas C Tempesti, María T Baumgartner
The worldwide increase in antibiotic resistance has led to search of alternatives anti-microbial therapies such as photodynamic inactivation. The aim of this paper was to evaluate the photodynamic activity in vitro of a neutral and two cationic Zn phthalocyanines. Their photokilling activity was tested on Escherichia coli ATCC 25922 and Klebsiella pneumoniae Carbapenemase (KPC)-producing. After treating bacteria with phthalocyanines, the cultures were irradiated with white light. As a result, the bacteria were inactivated in presence of cationic phthalocyanines...
September 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28844375/high-mortality-rate-associated-with-kpc-producing-enterobacter-cloacae-in-a-brazilian-hospital
#14
Kesia Esther da Silva, Tháigor Rezek Varella, Graciela Mendonça Dos Santos Bet, Cecília Godoy Carvalhaes, Maisa Estopa Correa, Nathalie Gaebler Vasconcelos, Julio Croda, Ana Cristina Gales, Simone Simionatto
We describe a clonal dissemination of KPC-producing Enterobacter cloacae in a Brazilian hospital. Patients diagnosed with theses isolates showed high mortality rate (41.8%) and were associated with previous use of antibiotics and urinary catheterization. Therefore, infection control measures and use of stricter antibiotic policies are required to control the spread of these organisms.
August 22, 2017: American Journal of Infection Control
https://www.readbyqxmd.com/read/28842811/imaging-of-claudin-4-in-pancreatic-ductal-adenocarcinoma-using-a-radiolabelled-anti-claudin-4-monoclonal-antibody
#15
Julia Baguña Torres, James C Knight, Michael J Mosley, Veerle Kersemans, Sofia Koustoulidou, Danny Allen, Paul Kinchesh, Sean Smart, Bart Cornelissen
PURPOSE: Despite its widespread use, the positron emission tomography (PET) radiotracer 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) has been shown in clinical settings to be ineffective for improving early diagnosis of pancreatic ductal adenocarcinoma (PDAC). A promising biomarker for PDAC detection is the tight junction protein claudin-4. The purpose of this study was to evaluate a new single-photon emission computed tomography (SPECT) imaging agent, [(111)In]anti-claudin-4 mAb, with regard to its ability to allow visualisation of claudin-4 in a xenograft and a genetically engineered mouse model of PDAC...
August 25, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28841710/inhibition-of-rock1-kinase-modulates-both-tumor-cells-and-stromal-fibroblasts-in-pancreatic-cancer
#16
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
#17
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
#18
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/28835096/reversibility-of-covalent-broad-spectrum-serine-%C3%AE-lactamase-inhibition-by-the-diazabicyclooctenone-etx2514
#19
Adam B Shapiro, Ning Gao, Haris Jahić, Nicole M Carter, April Chen, Alita A Miller
ETX2514 is a non-β-lactam serine β-lactamase inhibitor in clinical development that has greater potency and broader spectrum of β-lactamase inhibition than the related diazabicyclooctanone avibactam. Despite opening of its cyclic urea ring upon acylation, avibactam can recyclize and dissociate intact from certain β-lactamases. We investigated reversibility of ETX2514 acylation of 10 serine β-lactamases representing Ambler classes A, C, and D. Dissociation rate constants varied widely between enzymes and were lowest for class D...
August 28, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28827656/characterization-of-a-novel-class-a-carbapenemase-pad-1-from-paramesorhizobium-desertii-a-3-e-t-a-strain-highly-resistant-to-%C3%AE-lactam-antibiotics
#20
Ruichen Lv, Jingyu Guo, YanFeng Yan, Rong Chen, Lisheng Xiao, Min Wang, Nan Fang, Chengxiang Fang, Yujun Cui, Ruifu Yang, Yajun Song
Although clinical antibiotic-resistant bacteria have attracted tremendous attention in the microbiology community, the resistant bacteria that persist in natural environments have been overlooked for a longtime. We previously proposed a new species Paramesorhizobium desertii, isolated from the soil of the Taklimakan Desert in China that is highly resistant to most β-lactam antibiotics. To identify potential β-lactamase(s) in this bacteria, we first confirmed the carbapenemase activity in the freeze-thawed supernatant of a P...
August 21, 2017: Scientific Reports
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