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Hemilly Rayanne Ferreira da Silva, Marinalda Anselmo Vilela, Anna Carolina Soares Almeida, Márcia Maria Camargo de Morais
We describe colistin-resistant KPC-2-producing Klebsiella pneumoniae isolates from cerebrospinal fluid, belonging to ST423, selected during treatment for neuroinfection. Colistin resistance was related to mgrB gene interruption by an IS5-like.
February 2, 2018: Diagnostic Microbiology and Infectious Disease
Omnia A Shaker, Howayda E Gomaa, Shereen A ElMasry, Rania M Abdel Halim, Amany H Abdelrahman, Jackline S Kamal
AIM: To evaluate the diagnostic performance of MDI and temocillin disk (30 μg) for detection of carbapenem-resistant Enterobacteriaceae in comparison to real-time PCR. MATERIAL AND METHODS: Fifty specimens submitted to the Microbiology Laboratory of Ain Shams University Hospitals and showed resistance to carbapenem drugs through routine culture and susceptibility testing, were assessed by both temocillin disk (30 μg) and MDI set to detect carbapenem-resistant Enterobacteriaceae ...
February 15, 2018: Open Access Macedonian Journal of Medical Sciences
Martin Everett, Nicolas Sprynski, Alicia Coelho, Jérôme Castandet, Maëlle Bayet, Juliette Bougnon, Clarisse Lozano, David T Davies, Simon Leiris, Magdalena Zalacain, Ian Morrissey, Sophie Magnet, Kirsty Holden, Peter Warn, Filomena De Luca, Jean-Denis Docquier, Marc Lemonnier
Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent and have become a major worldwide threat to human health. Carbapenem resistance is driven primarily by the acquisition of β-lactamase enzymes which are able to degrade carbapenem antibiotics (hence termed carbapenemases) and can result in high levels of resistance and treatment failure. Clinically relevant carbapenemases include both serine-β-lactamases (SBLs, e.g. KPC-2 and OXA-48) and metallo-β-lactamases (MBLs), such as NDM-1...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Timothy Palzkill
The most common mechanism of resistance to β-lactam antibiotics in Gram-negative bacteria is the production of β-lactamases that hydrolyze the drugs. Class A β-lactamases are serine active-site hydrolases that include the common TEM, CTX-M, and KPC enzymes. The TEM enzymes readily hydrolyze penicillins and older cephalosporins. Oxyimino-cephalosporins, such as cefotaxime and ceftazidime, however, are poor substrates for TEM-1 and were introduced, in part, to circumvent β-lactamase-mediated resistance. Nevertheless, the use of these antibiotics has lead to evolution of numerous variants of TEM with mutations that significantly increase the hydrolysis of the newer cephalosporins...
2018: Frontiers in Molecular Biosciences
Fabio Arena, Tommaso Giani, Alberto Antonelli, Olga Lorenza Colavecchio, Patrizia Pecile, Bruno Viaggi, Riccardo Favilli, Gian Maria Rossolini
We evaluated the performance of an automated, rapid (TAT 4-8 h), liquid-culture method for carbapenem-resistant Enterobacteriaceae (CRE) detection from rectal swabs, in a setting of KPC-producing Klebsiella pneumoniae endemicity. With 600 samples (22 positive for CRE, 3.7%), the system sensitivity and specificity, at 8 h, were 100% and 99.2%, respectively.
March 7, 2018: Journal of Microbiological Methods
Michael A Pfaller, Michael D Huband, Rodrigo E Mendes, Robert K Flamm, Mariana Castanheira
We evaluated meropenem-vaborbactam activity against 11,559 Enterobacteriaceae isolates, including 330 carbapenem-resistant phenotypes (CRE) and carbapenemase genotypes collected worldwide during 2015. Meropenem-vaborbactam (inhibitor at 8 mg/L) and comparators were susceptibility tested using reference broth microdilution methods. CRE isolates were screened for the presence of genes encoding carbapenemases and 292 (88.5%) of the CRE isolates carried these resistance genes. A total of 209 (63.3% of the CRE; 1...
March 3, 2018: International Journal of Antimicrobial Agents
Bruna Fuga Araújo, Melina Lorraine Ferreira, Paola Amaral de Campos, Sabrina Royer, Iara Rossi Gonçalves, Deivid William da Fonseca Batistão, Miriam Rodriguez Fernandes, Louise Teixeira Cerdeira, Cristiane Silveira de Brito, Nilton Lincopan, Paulo Pinto Gontijo-Filho, Rosineide Marques Ribas
In this study, we describe the frequency of virulence genes in Klebsiella pneumoniae carbapenemase-2-producing Klebsiella pneumoniae (KPC-KP), including hypervirulent (hv) and hypermucoviscous (hm) strains by whole-genome sequencing. We also evaluate the capacity for biofilm formation by using phenotypic techniques. The occurrence of several virulence genes (fimABCDEFGHIK, mrkABCDFHJ, ecpA, wabG, entB, ugE, irp1, irp2, traT, iutA and ureADE) and a high frequency of hvhmKPC-KP isolates was found. Most hospital-associated lineages of KPC-KP belong to the international clonal group 258 (CG258)...
March 6, 2018: Journal of Medical Microbiology
Ryan K Shields, M Hong Nguyen, Liang Chen, Ellen G Press, Barry N Kreiswirth, Cornelius J Clancy
Ceftazidime-avibactam was used to treat 77 patients with carbapenem-resistant Enterobacteriaceae (CRE) infections at our center. Thirty- and 90-day survival rates were 81% and 69%, respectively; rates were higher than predicted by SAPS II and SOFA scores at the onset of infection. Clinical success was achieved in 55% of patients, but varied by site of infection. Success rates were lowest for pneumonia (36%) and higher for bacteremia (75%) and urinary tract infections (88%). By multivariate analysis, pneumonia ( P =0...
March 5, 2018: Antimicrobial Agents and Chemotherapy
Talayeh Tavakoly, Samar Jamali, Ali Mojtahedi, Mohammadali Khan Mirzaei, Mohammad Shenagari
Klebsiella pneumoniae is a Gram-negative bacterium which causes several human infections. Treatment of infections related to K. pneumoniae has become problematic, because of increasing trend of extended spectrum β-lactamases producing (ESBLs) strains. The present study was aimed to detect the prevalence of ESBL-producing Klebsiella spp. and KPC-2, CMY-2 and OXA-48 β-lactamase encoding genes in clinical isolates of Klebsiella spp. isolated from hospitalized patients. In this cross-sectional study carried out from February to August 2014, 144 isolates of Klebsiella spp...
February 28, 2018: Cellular and Molecular Biology
Bruce L Geller, Lixin Li, Fabian Martinez, Erin Sully, Carolyn R Sturge, Seth M Daly, Christine Pybus, David E Greenberg
Background: Klebsiella pneumoniae is an opportunistic pathogen and many strains are multidrug resistant. KPC is one of the most problematic resistance mechanisms, as it confers resistance to most β-lactams, including carbapenems. A promising platform technology for treating infections caused by MDR pathogens is the nucleic acid-like synthetic oligomers that silence bacterial gene expression by an antisense mechanism. Objectives: To test a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) in a mouse model of K...
March 1, 2018: Journal of Antimicrobial Chemotherapy
Marisa F Nicolás, Pablo Ivan Pereira Ramos, Fabíola Marques de Carvalho, Dhian R A Camargo, Carlene de Fátima Morais Alves, Guilherme Loss de Morais, Luiz G P Almeida, Rangel C Souza, Luciane P Ciapina, Ana C P Vicente, Roney S Coimbra, Ana T Ribeiro de Vasconcelos
The aim of this study was to unravel the genetic determinants responsible for multidrug (including carbapenems) resistance and virulence in a clinical isolate of Klebsiella quasipneumoniae subsp. similipneumoniae by whole-genome sequencing and comparative analyses. Eighty-three clinical isolates initially identified as carbapenem-resistant K. pneumoniae were collected from nosocomial infections in southeast Brazil. After RAPD screening, the KPC-142 isolate, showing the most divergent DNA pattern, was selected for complete genome sequencing in an Illumina HiSeq 2500 instrument...
2018: Frontiers in Microbiology
Maria Giufrè, Giulia Errico, Marisa Accogli, Monica Monaco, Laura Villa, Maria Antonietta Distasi, Tito Del Gaudio, Annalisa Pantosti, Alessandra Carattoli, Marina Cerquetti
The emergence of carbapenemase-producing Enterobacteriaceae (CPE) is a critical concern worldwide. In Italy, CPE isolates are very frequent with the KPC types strongly predominant whereas the New Delhi metallo-β-lactamase (NDM) enzymes are extremely rare. In this study, we report the first detection of NDM-5-producing Escherichia coli sequence type (ST) 167 isolates from two patients with urinary tract infection (Ec001and Ec002 from urines) including one with colonization (Ec003 from faeces) admitted to the same hospital in 2017 two months apart...
February 28, 2018: International Journal of Antimicrobial Agents
Norelle L Sherry, Sarah L Baines, Benjamin P Howden
Avibactam is a novel β-lactamase inhibitor active against classes A, C and some class D β-lactamases. In combination with ceftazidime, it may be useful for the treatment of infections due to carbapenemase-producing Gram negative (CPGN) bacteria from these classes; however, susceptibility data for some of the less-common carbapenemases are limited. To assess the in vitro activity of ceftazidime-avibactam (CZA), we tested a panel of fifty diverse CPGN collected from clinical isolates in Victoria, Australia, containing KPC, GES, SME, OXA-23 and OXA-48-like carbapenemases for CZA susceptibility using broth microdilution (BMD), E-tests and disc diffusion...
February 27, 2018: International Journal of Antimicrobial Agents
Hanna E Sidjabat, Jolene Gien, David Kvaskoff, Keith Ashman, Kanchan Vaswani, Sarah Reed, Ross P McGeary, David L Paterson, Amanda Bordin, Gerhard Schenk
Antibiotic resistance associated with the clinically significant carbapenemases KPC, NDM and OXA-48 in Enterobacteriaceae is emerging as worldwide. In Australia, IMP-producing Enterobacteriaceae are the most prevalent carbapenemase-producing Enterobacteriaceae (CPE). Genomic characteristics of such CPE are well described, but the corresponding proteome is poorly characterised. We have thus developed a method to analyse dynamic changes in the proteome of CPE under antibiotic pressure. Specifically, we have investigated the effect of meropenem at sub-lethal concentrations to develop a better understanding of how antibiotic pressure leads to resistance...
March 1, 2018: Scientific Reports
Irene Sangrador, Xavier Molero, Fiona Campbell, Sebastià Franch-Expósito, Maria Rovira-Rigau, Esther Samper, Manuel Domínguez Fraile, Cristina Fillat, Antoni Castells, Eva C Vaquero
The transcription factor Zeb1 has been identified as a crucial player in Kras-dependent oncogenesis. In pancreatic ductal adenocarcinoma (PDAC), Zeb1 is highly expressed in myofibroblasts and correlates with poor prognosis. As Kras mutations are key drivers in PDAC, we aimed here to assess the necessity of Zeb1 for Kras-driven PDAC and to define the role of Zeb1-expressing myofibroblasts in PDAC development. Genetically engineered mice with conditional pancreatic KrasG12D and Trp53 mutations (KPC) were crossed with Zeb1 haploinsufficient mice (Z+/-)...
February 28, 2018: Cancer Research
Alejandra Vera-Leiva, Carla Barría-Loaiza, Sergio Carrasco-Anabalón, Celia Lima, Alejandro Aguayo-Reyes, Mariana Domínguez, Helia Bello-Toledo, Gerardo González-Rocha
The dissemination of carbapenemase-producing Enterobacteriaceae is currently considered a serious clinical problem due to the failure in the treatment of infections produced by them. Among the carbapenemases, the enzyme KPC has spread worldwide and has been identified in the main enterobacterial species related with healthcareassociated infections, although Klebsiella pneumoniae is the predominant specie. The blaKPC gene is transported, mainly by the transposon Tn4401, detected in various enterobacterial species of different sequence types (ST) and geographical origin...
October 2017: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
Zackery P Bulman, Miao Zhao, Michael J Satlin, Liang Chen, Barry N Kreiswirth, Thomas J Walsh, Roger L Nation, Jian Li, Brian T Tsuji
Polymyxin B and fosfomycin are two 'old' antibiotics that consistently maintain activity against Klebsiella pneumoniae carbapenemase (KPC)-producing organisms based on in vitro susceptibility testing. However, each antibiotic's use in monotherapy has been associated with high rates of treatment failure. Therefore, our objective was to investigate the combinatorial pharmacodynamics of polymyxin B and fosfomycin against KPC-producing K. pneumoniae. Polymyxin B front-loading (3.33 mg/kg for 1 dose followed by 1...
February 24, 2018: International Journal of Antimicrobial Agents
Guillaume Gautier, Thomas Guillard, Bianca Podac, Béatrice Bercot, Véronique Vernet-Garnier, Christophe de Champs
A new phenotypic method for detecting carbapenemases has been adapted (assembling of two MAST® kits, including one that contains faropenem to which a temocillin disk has been added) then assessed using 101 bacterial strains (Enterobacteriaceae with assays on Pseudomonas aeruginosa and Acinetobacter baumannii) including 62 which produce genetically identified carbapenemases. Concerning Carbapenemase-Producing Enterobacteriaceae (CPE), there is 100% sensitivity for Klebsiella pneumoniae carbapenemase (KPC, Ambler class A) and OXA-48 (Ambler class D), and 91% for metallo-beta-lactamase (MBL, Ambler class B), with a 97% sensitivity for all carbapenemases, with a specificity of 100%...
February 24, 2018: Journal of Microbiological Methods
Jade E McLellan, Joshua I Pitcher, Susan A Ballard, Elizabeth A Grabsch, Jan M Bell, Mary Barton, M Lindsay Grayson
Background: Antibiotic misuse in food-producing animals is potentially associated with human acquisition of multidrug-resistant (MDR; resistance to ≥ 3 drug classes) bacteria via the food chain. We aimed to determine if MDR Gram-negative (GNB) organisms are present in fresh Australian chicken and pork products. Methods: We sampled raw, chicken drumsticks (CD) and pork ribs (PR) from 30 local supermarkets/butchers across Melbourne on two occasions. Specimens were sub-cultured onto selective media for third-generation cephalosporin-resistant (3GCR) GNBs, with species identification and antibiotic susceptibility determined for all unique colonies...
2018: Antimicrobial Resistance and Infection Control
Ryota Gomi, Tomonari Matsuda, Masaki Yamamoto, Pei-Hsin Chou, Michio Tanaka, Satoshi Ichiyama, Minoru Yoneda, Yasufumi Matsumura
Wastewater is considered a major source of antibiotic-resistant bacteria released into the environment. Here, we characterized carbapenemase-producing Enterobacteriaceae (CPE) in wastewater by whole-genome analysis. Wastewater samples (n = 40) were collected from municipal wastewater treatment plants and hospital wastewater in Japan and Taiwan. Samples were screened for CPE using selective media, and the obtained isolates were sequenced using an Illumina MiSeq. The isolates (n = 45) included the following microorganisms: Klebsiella quasipneumoniae (n = 12), Escherichia coli (n = 10), Enterobacter cloacae complex (n = 10), Klebsiella pneumoniae (n = 8), Klebsiella variicola (n = 2), Raoultella ornithinolytica (n = 1), Citrobacter freundii (n = 1), and Citrobacter amalonaticus (n = 1)...
February 26, 2018: Antimicrobial Agents and Chemotherapy
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