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Scott D Kobayashi, Adeline R Porter, Brett Freedman, Ruchi Pandey, Liang Chen, Barry N Kreiswirth, Frank R DeLeo
Carbapenem-resistant Klebsiella pneumoniae is a problem worldwide. A carbapenem-resistant K. pneumoniae lineage classified as multilocus sequence type 258 (ST258) is prominent in the health care setting in many regions of the world, including the United States. ST258 strains can be resistant to virtually all clinically useful antibiotics; treatment of infections caused by these organisms is difficult, and mortality is high. As a step toward promoting development of new therapeutics for ST258 infections, we tested the ability of rabbit antibodies specific for ST258 capsule polysaccharide to enhance human serum bactericidal activity and promote phagocytosis and killing of these bacteria by human neutrophils...
March 13, 2018: MBio
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
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
Miranda E Pitt, Alysha G Elliott, Minh Duc Cao, Devika Ganesamoorthy, Ilias Karaiskos, Helen Giamarellou, Cely S Abboud, Mark A T Blaskovich, Matthew A Cooper, Lachlan J M Coin
Extensively drug-resistant Klebsiella pneumoniae (XDR-KP) infections cause high mortality and are disseminating globally. Identifying the genetic basis underpinning resistance allows for rapid diagnosis and treatment. XDR isolates sourced from Greece and Brazil, including 19 polymyxin-resistant and five polymyxin-susceptible strains, were subjected to whole genome sequencing. Seventeen of the 19 polymyxin-resistant isolates harboured variations upstream or within mgrB. The most common mutation identified was an insertion at nucleotide position 75 in mgrB via an ISKpn26-like element in the ST258 lineage and ISKpn13 in one ST11 isolate...
February 12, 2018: Microbial Genomics
Ning Dong, Rong Zhang, Lizhang Liu, Ruichao Li, Dachuan Lin, Edward Wai-Chi Chan, Sheng Chen
The increasing prevalence of KPC-producing Klebsiella pneumoniae strains in clinical settings has been largely attributed to dissemination of organisms of specific multilocus sequence types, such as ST258 and ST11. Compared with the ST258 clone, which is prevalent in North America and Europe, ST11 is common in China but information regarding its genetic features remains scarce. In this study, we performed detailed genetic characterization of ST11 K. pneumoniae strains by analyzing whole-genome sequences of 58 clinical strains collected from diverse geographic locations in China...
February 8, 2018: Microbial Genomics
Marla J Giddins, Nenad Macesic, Medini K Annavajhala, Stephania Stump, Sabrina Khan, Thomas H McConville, Monica Mehta, Angela Gomez-Simmonds, Anne-Catrin Uhlemann
Ceftazidime-avibactam (CAZ/AVI) is a promising novel treatment for carbapenem-resistant Enterobacteriaceae (CRE). Despite improved treatment outcomes compared to aminoglycoside- and colistin-based regimens, rapid evolution of CAZ/AVI resistance during treatment has previously been reported in Klebsiella pneumoniae ST258 blaKPC-3 harboring isolates. Here, we report the step-wise evolution and isolation of two phenotypically distinct CAZ/AVI resistant Klebsiella pneumoniae phenotypes from a patient with pancreatitis...
December 20, 2017: Antimicrobial Agents and Chemotherapy
Denise De Belder, Celeste Lucero, Melina Rapoport, Adriana Rosato, Diego Faccone, Alejandro Petroni, Fernando Pasteran, Ezequiel Albornoz, Alejandra Corso, Sonia A Gomez
The predominance of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae was caused by the spread of ST258 clone. In Latin America, KPC was reported in 2006, with the isolation of genetically unrelated K. pneumoniae in Colombia. Since then, the expansion of blaKPC in either K. pneumoniae ST258 or other Enterobacteriaceae (ETB) species was increasingly reported. In this study, we characterized 89 KPC-producing Escherichia coli, Klebsiella oxytoca, Serratia marcescens, and Citrobacter freundii that were received between 2010 and 2014...
December 13, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Mariasofia Caltagirone, Elisabetta Nucleo, Melissa Spalla, Francesca Zara, Federica Novazzi, Vittoria M Marchetti, Aurora Piazza, Ibrahim Bitar, Marica De Cicco, Stefania Paolucci, Giorgio Pilla, Roberta Migliavacca, Laura Pagani
To evaluate the water compartment antibiotic-resistance contamination rates, 11 wells, five streams, and four treatment plants located in the Oltrepò Pavese area were screened for the presence of third generation cephalosporins resistant Gram-negative bacteria. Enterobacteriaceae were also characterized for the Extended-Spectrum-β-Lactamases (ESBLs), carbapenemases, and mcr-1 genes presence. From December 2014 to November 2015, 246 water samples were filtered, plated on Plate Count Agar, MacConkey Agar, and MacConkey Agar with cefotaxime...
2017: Frontiers in Microbiology
G Ventrella, A Moodley, E Grandolfo, A Parisi, M Corrente, D Buonavoglia, L Guardabassi
In the last decade there has been a rapid global spread of methicillin-resistant Staphylococcus pseudintermedius (MRSP) clones displaying multidrug resistance in dogs. We investigated prevalence, antimicrobial susceptibility and clonal distribution of MRSP isolated from clinical canine samples between during 2011-2014. Following species identification by nuc PCR, MRSP were confirmed by the presence of mecA and characterized by antimicrobial susceptibility testing, Pulsed Field Gel Electrophoresis (PFGE), SCCmec typing, and Multi-Locus Sequence Typing (MLST) of a few isolates having distinct PFGE profiles...
November 2017: Veterinary Microbiology
Cesira Giordano, Simona Barnini, Constantinos Tsioutis, Monika A Chlebowicz, Effie V Scoulica, Achilleas Gikas, John W Rossen, Alexander W Friedrich, Erik Bathoorn
BACKGROUND: mcr-1 has been reported as first plasmid gene to confer colistin-resistance. In KPC-producing Klebsiella pneumoniae (KPC-KP) isolates, however, colistin resistance is rapidly emerging through other mechanisms. This is frequently the result of disruption of mgrB gene by insertion sequences, for instance ISL3. The aim of this study is to investigate the expansion of mgrB-mutated KPC-KP. In addition, we identify localization and targets of ISL3 sequences within the core and accessory genome of common KPC-KP lineages...
October 27, 2017: International Journal of Antimicrobial Agents
Laura J Rojas, George M Weinstock, Elsa De La Cadena, Lorena Diaz, Rafael Rios, Blake M Hanson, Joseph S Brown, Purva Vats, Daniel S Phillips, Hoan Nguyen, Kristine M Hujer, Adriana Correa, Mark D Adams, Federico Perez, Erica Sodergren, Apurva Narechania, Paul J Planet, Maria V Villegas, Robert A Bonomo, Cesar A Arias
Background: Carbapenem resistance is a critical health care challenge worldwide. Particularly concerning is the widespread dissemination of Klebsiella pneumoniae carbapenemase (KPC). K. pneumoniae harboring blaKPC (KPC-Kpn) is endemic in many areas including United States, where the epidemic was primarily mediated by the clonal dissemination of Kpn ST258. We postulated that the spread of blaKPC in other regions occurs by different and more complex mechanisms. To test this, we investigated the evolution and dynamics of spread of KPC-Kpn in Colombia, where KPC became rapidly endemic after emerging in 2005...
September 27, 2017: Journal of Infectious Diseases
Guilherme Bartolomeu Gonçalves, João Pedro Rueda Furlan, Eliana Carolina Vespero, Marsileni Pelisson, Eliana Guedes Stehling, André Pitondo-Silva
Klebsiella pneumoniae is among the most important pathogens found in hospitals. The emergence of multiple antibiotic resistant K. pneumoniae associated with its virulence factors is a worldwide concern and its early identification is crucial, especially for controlling the spread of emerging clones. This article reports a high prevalence of multiresistant K. pneumoniae in a university hospital in southern Brazil, harboring several virulence and β-lactamase encoding genes, including pandrug-resistant high-risk international clones belonging to the clonal group 258 (ST11, ST15, ST101, ST258, ST340 and ST874)...
December 2017: Infection, Genetics and Evolution
Magdalena Kizerwetter-Świda, Dorota Chrobak-Chmiel, Magdalena Rzewuska, Marian Binek
Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is being reported with an increasing frequency in small animal veterinary practice. The molecular typing of MRSP isolates revealed that the dominating European multidrug-resistant lineage is the sequence type 71 (ST71), associated with staphylococcal chromosomal cassette SCCmec type II-III. However, the recent reports indicated the emergence of other clones. The study aimed to determine the genetic properties of MRSP isolates obtained from dogs in Poland over a ten-year period...
September 2017: Veterinary Microbiology
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
Laura Villa, Claudia Feudi, Daniela Fortini, Sylvain Brisse, Virginie Passet, Celestino Bonura, Andrea Endimiani, Caterina Mammina, Ana Maria Ocampo, Judy Natalia Jimenez, Michel Doumith, Neil Woodford, Katie Hopkins, Alessandra Carattoli
The global spread of Klebsiella pneumoniae producing Klebsiella pneumoniae carbapenemase (KPC) has been mainly associated with the dissemination of high-risk clones. In the last decade, hospital outbreaks involving KPC-producing K. pneumoniae have been predominantly attributed to isolates belonging to clonal group (CG) 258. However, results of recent epidemiological analysis indicate that KPC-producing sequence type (ST) 307, is emerging in different parts of the world and is a candidate to become a prevalent high-risk clone in the near future...
April 2017: Microbial Genomics
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)
Ann Maria Clemente, Giuseppe Castronovo, Alberto Antonelli, Marco Maria D'Andrea, Michele Tanturli, Eloisa Perissi, Sara Paccosi, Astrid Parenti, Federico Cozzolino, Gian Maria Rossolini, Maria Gabriella Torcia
The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model...
2017: PloS One
Angela Gomez-Simmonds, Anne-Catrin Uhlemann
Klebsiella pneumoniae poses a major challenge to healthcare worldwide as an important cause of multidrug-resistant infections. Nosocomial clones, including epidemic sequence type 258 (ST258), have shown an affinity for acquiring and disseminating resistance plasmids, particularly variants of the K. pneumoniae carbapenemase. By comparison, the resurgence of severe community-associated K. pneumoniae infections has led to increased recognition of hypervirulent strains belonging to the K1 and K2 capsular serotypes, predominantly in eastern Asia...
February 15, 2017: Journal of Infectious Diseases
Mark D Adams, Brian Bishop, Meredith S Wright
Insertion sequence (IS) elements are important mediators of genome plasticity and can lead to phenotypic changes with evolutionary significance. In multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae, IS elements have contributed significantly to the mobilization of genes that encode resistance to antimicrobial drugs. A systematic analysis of IS elements is needed for a more comprehensive understanding of their evolutionary impact. We developed a computational approach (ISseeker) to annotate IS elements in draft genome assemblies and applied the method to analysis of IS elements in all publicly available A...
July 2016: Microbial Genomics
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
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