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https://www.readbyqxmd.com/read/28470337/synergistic-activity-of-synthetic-n-terminal-peptide-of-human-lactoferrin-in-combination-with-various-antibiotics-against-carbapenem-resistant-klebsiella-pneumoniae-strains
#1
P Morici, W Florio, C Rizzato, E Ghelardi, A Tavanti, G M Rossolini, A Lupetti
The spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1-11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin)...
May 3, 2017: European Journal of Clinical Microbiology & Infectious Diseases
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
#2
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/28458208/international-high-risk-clones-of-klebsiella-pneumoniae-kpc-2-cc258-and-escherichia-coli-ctx-m-15-cc10-in-urban-lake-waters
#3
Tatiane Nascimento, Rodrigo Cantamessa, Luana Melo, Miriam R Fernandes, Edmir Fraga, Milena Dropa, Maria I Z Sato, Louise Cerdeira, Nilton Lincopan
The emergence of high-risk clones of multidrug-resistant (MDR) bacteria in aquatic environments has generated an important public health problem, creating an urgent need to strengthen surveillance. This study reports the occurrence of clinically significant MDR Enterobacteriaceae and non-fermentative bacteria carrying carbapenemases (KPC-2), extended-spectrum β-lactamases (CTX-M) and plasmid-mediated quinolone resistance (PMQR) genes in urban lakes and reservoirs, in Southeastern Brazil. In this regard, the detection of hospital-associated lineages of KPC-2-producing Klebsiella pneumoniae belonging to the international clonal complex CC258 (ST11) and CTX-M-15-producing Escherichia coli belonging to the international CC10 (ST617), in an urban lake, is reported for the first time...
April 27, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28444224/pharmacodynamics-of-colistin-and-fosfomycin-a-treasure-trove-combination-combats-kpc-producing-klebsiella-pneumoniae
#4
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/28442305/transfer-of-kpc-2-carbapenemase-from-klebsiella-pneumoniae-to-enterobacter-cloacae-in-a-patient-receiving-meropenem-therapy
#5
Evelin Rodrigues Martins, Cássia Fernanda Estofolete, Andressa Batista Zequini, Louise Cerdeira, Doroti de Oliveira Garcia, Maria Fernanda Campagnari Bueno, Gabriela Rodrigues Francisco, Leonardo Neves de Andrade, Ana Lúcia da Costa Darini, Fernanda Modesto Tolentino, Tiago Casella, Nilton Lincopan, Mara Corrêa Lelles Nogueira
The horizontal transfer of a plasmid bearing the blaKPC-2 gene from K. pneumoniae to E. cloacae infecting the respiratory tract of a patient during meropenem therapy was elucidated. This finding is particularly worrisome, since these drugs are of last resort for multidrug-resistant Gram-negative pathogens.
April 12, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28438940/emergence-of-plasmid-mediated-mcr-1-gene-in-clinical-kpc-2-producing-klebsiella-pneumoniae-st392-in-brazil
#6
Caio Augusto Martins Aires, Orlando Carlos da Conceição-Neto, Thamirys Rachel Tavares E Oliveira, Carolina Frizzera Dias, Lara Feital Montezzi, Renata Cristina Picão, Rodolpho Mattos Albano, Marise Dutra Asensi, Ana Paula D'Alincourt Carvalho-Assef
Since the first report of the plasmid-mediated colistin resistance mcr-1 gene in Escherichia coli and Klebsiella pneumoniae isolates from China (1), mcr-1 had already spread to most continents, being detected in different species from several sources, including in carbapenemase-producing clinical isolates (2).….
April 24, 2017: Antimicrobial Agents and 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
#7
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/28429335/imipenem-resistance-in-serratia-marcescens-is-mediated-by-plasmid-expression-of-kpc-2
#8
W-Q Su, Y-Q Zhu, N-M Deng, L Li
OBJECTIVE: Imipenem is a broad-spectrum carbapenem antibiotic with applications against severe bacterial infections. Here, we describe the identification of imipenem-resistant Serratia marcescens in our hospital and the role of plasmid-mediated KPC-2 expression in imipenem resistance. MATERIALS AND METHODS: We used the modified Hodge test to detect carbapenemase produced in imipenem-resistant strains. RESULTS: His resistance can be transferred to E...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28425875/occurrence-of-qnrb1-and-qnrb12-genes-mutation-in-gyra-and-ramr-and-expression-of-efflux-pumps-in-isolates-of-klebsiella-pneumoniae-carriers-of-blakpc-2
#9
Alexsandra Maria Lima Scavuzzi, Maria Amélia Vieira Maciel, Heloísa Ramos Lacerda de Melo, Luiz Carlos Alves, Fábio André Brayner, Ana Catarina Souza Lopes
PURPOSE: The occurrence of quinolone-resistance genes (qnrA, qnrB and qnrS), the presence of mutations in gyrA, gyrB and parC, as well as the expression of efflux pumps (acrB and acrF) and mutations in the gene ramR. METHODOLOGY: Were investigated in 30 blaKPC-2-positive isolates of Klebsiella pneumoniae taken from infection and colonization in hospital patients from Recife-PE, Brazil. The detection of the qnr, acrB and acrF genes and analysis of the mutations in ramR and the quinolone-resistance-determining regions of gyrA, gyrB and parC were performed by PCR followed by DNA sequencing...
April 21, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28388065/molecular-basis-of-substrate-recognition-and-product-release-by-the-klebsiella-pneumoniae-carbapenemase-kpc-2
#10
Orville A Pemberton, Xiujun Zhang, Yu Chen
Carbapenem-resistant Enterobacteriaceae are resistant to most β-lactam antibiotics due to the production of the Klebsiella pneumoniae carbapenemase (KPC-2) class A β-lactamase. Here, we present the first product complex crystal structures of KPC-2 with β-lactam antibiotics containing hydrolyzed cefotaxime and faropenem. They provide experimental insights into substrate recognition by KPC-2 and its unique cephalosporinase/carbapenemase activity. These structures also represent the first product complexes for a wild-type serine β-lactamase, elucidating the product release mechanism of these enzymes in general...
April 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28380016/carbapenemase-producing-enterobacteriaceae-recovered-from-a-spanish-river-ecosystem
#11
Núria Piedra-Carrasco, Anna Fàbrega, William Calero-Cáceres, Thais Cornejo-Sánchez, Maryury Brown-Jaque, Alba Mir-Cros, Maite Muniesa, Juan José González-López
The increasing resistance to carbapenems is an alarming threat in the fight against multiresistant bacteria. The dissemination properties of antimicrobial resistance genes are supported by their detection in a diverse population of bacteria, including strains isolated from the environment. The objective of this study was to investigate the presence of carbapenemase-producing Enterobacteriaceae (CPE) collected from a river ecosystem in the Barcelona metropolitan area (Spain). Identification of β-lactamases and other resistance determinants was determined as was the antimicrobial susceptibility profile...
2017: PloS One
https://www.readbyqxmd.com/read/28333348/promoter-characterization-and-expression-of-the-blakpc-2-gene-in-escherichia-coli-pseudomonas-aeruginosa-and-acinetobacter-baumannii
#12
Delphine Girlich, Rémy A Bonnin, Agnes Jousset, Thierry Naas
Objectives: KPC-producing pathogens exhibit variable carbapenem susceptibility levels, which is probably the result of the genetic environment of the bla KPC genes. Here we determined the transcriptional start sites (TSSs) and the expression of the bla KPC-2 gene in various genetic contexts and in different hosts ( Escherichia coli , Pseudomonas aeruginosa and Acinetobacter baumannii ). Methods: The bla KPC-2 genes along with the upstream sequences derived from Tn 4401b (structure A), Tn 4401b interrupted by Tn 3 /IS 26 (structure B) and Tn 4401b interrupted by Tn 5563 (structure C) were cloned in two E...
June 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28333331/multiregional-dissemination-of-kpc-producing-klebsiella-pneumoniae-st258-st512-genotypes-in-poland-2010-14
#13
Anna Baraniak, Radoslaw Izdebski, Dorota Zabicka, Katarzyna Bojarska, Sandra Górska, Elzbieta Literacka, Janusz Fiett, Waleria Hryniewicz, Marek Gniadkowski
Objectives: In 2008-09, the KPC carbapenemase epidemiology in Poland was dominated by a Klebsiella pneumoniae ST258 KPC-2 outbreak in Warsaw and its administrative region. The aim of this study was to analyse the situation in 2010-14, with a focus on new outbreaks in other parts of the country. Methods: KPCs were detected in all suspected isolates by PCR. The detailed study was performed on 173 isolates from 2010 to 2012, and included PFGE and MLST, PCR identification of K...
June 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28264645/systematic-substitutions-at-blip-position-50-result-in-changes-in-binding-specificity-for-class-a-%C3%AE-lactamases
#14
Carolyn J Adamski, Timothy Palzkill
BACKGROUND: The production of β-lactamases by bacteria is the most common mechanism of resistance to the widely prescribed β-lactam antibiotics. β-lactamase inhibitory protein (BLIP) competitively inhibits class A β-lactamases via two binding loops that occlude the active site. It has been shown that BLIP Tyr50 is a specificity determinant in that substitutions at this position result in large differential changes in the relative affinity of BLIP for class A β-lactamases. RESULTS: In this study, the effect of systematic substitutions at BLIP position 50 on binding to class A β-lactamases was examined to further explore the role of BLIP Tyr50 in modulating specificity...
March 6, 2017: BMC Biochemistry
https://www.readbyqxmd.com/read/28242657/tn6350-a-novel-transposon-carrying-pyocin-s8-genes-encoding-a-bacteriocin-with-activity-against-carbapenemase-producing-pseudomonas-aeruginosa
#15
Helena Turano, Fernando Gomes, Gesiele A Barros-Carvalho, Ralf Lopes, Louise Cerdeira, Luis E S Netto, Ana C Gales, Nilton Lincopan
A novel transposon belonging to the Tn3-like family was identified on the chromosome of a commensal strain of Pseudomonas aeruginosa sequence type 2343 (ET02). Tn6350 is 7,367 bp long and harbors eight open reading frames (ORFs), an ATPase (IS481 family), a transposase (DDE catalytic type), a Tn3 resolvase, three hypothetical proteins, and genes encoding the new pyocin S8 with its immunity protein. We show that pyocin S8 displays activity against carbapenemase-producing P. aeruginosa, including IMP-1, SPM-1, VIM-1, GES-5, and KPC-2 producers...
May 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28219824/characterisation-of-the-first-kpc-2-producing-klebsiella-pneumoniae-st340-from-peru
#16
Gertrudis Horna, Jorge Velasquez, Nathaly Fernández, Jesus Tamariz, Joaquim Ruiz
OBJECTIVES: The aim of this study was to characterise a KPC-carrying Klebsiella pneumoniae isolate from a Peruvian hospital setting. METHODS: The identity of the isolate was confirmed by amplification and sequencing of the 16S rRNA gene, and the antibiotic resistance profile was determined by disk diffusion and automated methods The sequence type (ST) and phylogenetic group were established by PCR. The presence of different β-lactamase genes was determined, including blaMBL, blaKPC, blaCTX-M, blaSHV, blaOXA-1-like, blaOXA-2-like, blaOXA-5-like, blaOXA-48-like and blaTEM and up to six different plasmid-encoded AmpC genes as well as class 1 integrons...
February 20, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28210888/double-carbapenem-combination-as-salvage-therapy-for-untreatable-infections-by-kpc-2-producing-klebsiella-pneumoniae
#17
M Souli, I Karaiskos, A Masgala, L Galani, E Barmpouti, H Giamarellou
We report our experience using the double-carbapenem combination as salvage therapy for patients with untreatable infections caused by KPC-2- producing Klebsiella pneumoniae. A total of 27 patients in two institutions in Athens, Greece suffering from complicated urinary tract infections (16) with or without secondary bacteraemia (four and 12 respectively), primary (six) or catheter-related bloodstream infections (two), HAP or VAP (two) and external ventricular drainage infection (one) were treated exclusively with ertapenem and high-dose prolonged infusion meropenem because in-vitro active antimicrobials were unavailable (19) or failed (four) or were contraindicated (six)...
February 16, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28185686/outbreak-of-kpc-2-producing-enterobacteriaceae-caused-by-clonal-dissemination-of-klebsiella-pneumoniae-st307-carrying-an-incx3-type-plasmid-harboring-a-truncated-tn4401a
#18
Jung Ok Kim, Sae Am Song, Eun-Jeong Yoon, Jeong Hwan Shin, Hyukmin Lee, Seok Hoon Jeong, Kyungwon Lee
Over a 5-month period between the end of June and the beginning of November in 2015, a KPC-producing Enterobacteriaceae outbreak occurred in a general hospital in Busan, South Korea, being associated with a total of 50 clinical isolates from 47 patients. Multilocus sequence typing and pulsed-field gel electrophoresis were carried out for strain typing and whole-genome sequencing was performed to characterize the plasmids. A clonal spread of K. pneumoniae sequence type 307 (ST307) carrying a self-transferable IncX3-type plasmid harboring blaKPC-2 was responsible for the outbreak...
April 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28167551/genomic-characterization-of-two-kpc-producing-klebsiella-isolates-collected-in-1997-in-new-york-city
#19
Brandon Eilertson, Liang Chen, Kalyan D Chavda, Barry N Kreiswirth
Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have now become a global public health threat. However, the origin of this pandemic and the characterization of pre-2003 blaKPC-harboring plasmids remain unknown. Here we used next-generation sequencing to characterize two KPC-2-producing K. pneumoniae and Kmichiganensis isolates collected from a New York City hospital in 1997. Although identified in two different Klebsiella species, the blaKPC-2 gene was harbored by Tn4401b transposons on two highly similar IncN plasmids...
April 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28167549/new-polymyxin-b-dosing-strategies-to-fortify-old-allies-in-the-war-against-kpc-2-producing-klebsiella-pneumoniae
#20
Zackery P Bulman, Michael J Satlin, Liang Chen, Barry N Kreiswirth, Beom Soo Shin, Thomas J Walsh, Patricia N Holden, Alan Forrest, Roger L Nation, Jian Li, Brian T Tsuji
Pharmacodynamics of a polymyxin B, meropenem, and rifampin triple combination were examined against Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) ST258. In time-kill experiments against three KPC-Kp isolates, triple combination generated 8.14, 8.19, and 8.29 log10 CFU/ml reductions within 24 h. In the hollow-fiber infection model, the triple combination caused maximal killing of 5.16 log10 CFU/ml at 78 h and the time required for regrowth was more than doubled versus the 2-drug combinations...
April 2017: Antimicrobial Agents and Chemotherapy
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