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https://www.readbyqxmd.com/read/28198411/the-secondary-resistome-of-multidrug-resistant-klebsiella-pneumoniae
#1
Bimal Jana, Amy K Cain, William T Doerrler, Christine J Boinett, Maria C Fookes, Julian Parkhill, Luca Guardabassi
Klebsiella pneumoniae causes severe lung and bloodstream infections that are difficult to treat due to multidrug resistance. We hypothesized that antimicrobial resistance can be reversed by targeting chromosomal non-essential genes that are not responsible for acquired resistance but essential for resistant bacteria under therapeutic concentrations of antimicrobials. Conditional essentiality of individual genes to antimicrobial resistance was evaluated in an epidemic multidrug-resistant clone of K. pneumoniae (ST258)...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167556/the-importance-of-clonal-complex-258-and-incfk2-like-plasmids-among-a-global-collection-of-klebsiella-pneumoniae-with-blakpcs
#2
Gisele Peirano, Patricia A Bradford, Krystyna M Kazmierczak, Liang Chen, Barry N Kreiswirth, Johann D D Pitout
This study was designed to determine the global distribution of clonal complex (CC) 258 and IncFIIK2-like plasmids with blaKPC among 522 global KPC-producing K. pneumoniae CC258 (i.e. ST258 [clades I and II], ST11, ST512) and ST147 were statistically associated with IncFIIK2-like KPC-containing plasmids and may possess an epidemiological advantage over isolates that harboured non-IncF KPC-harboring plasmids.
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28167549/polymyxin-b-based-triple-combinations-wage-war-against-kpc-2-producing-klebsiella-pneumoniae-new-dosing-strategies-for-old-allies
#3
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 log10CFU/mL reductions within 24h. In the hollow fiber infection model, the triple combination caused maximal killing of 5.16 log10CFU/mL at 78h and time required for regrowth was more than doubled versus 2-drug combinations...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28167547/bacteremia-due-to-carbapenem-resistant-enterobacteriaceae-cre-a-multicenter-clinical-and-molecular-epidemiologic-analysis-in-the-nation-s-epicenter-for-cre
#4
Michael J Satlin, Liang Chen, Gopi Patel, Angela Gomez-Simmonds, Gregory Weston, Angela C Kim, Susan K Seo, Marnie E Rosenthal, Steven J Sperber, Stephen G Jenkins, Camille L Hamula, Anne-Catrin Uhlemann, Michael H Levi, Bettina C Fries, Yi-Wei Tang, Stefan Juretschko, Albert D Rojtman, Tao Hong, Barun Mathema, Michael R Jacobs, Thomas J Walsh, Robert A Bonomo, Barry N Kreiswirth
Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or transplantation...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28167543/carbapenem-minimal-inhibitory-concentrations-in-escherichia-coli-and-klebsiella-species-producing-extended-spectrum-beta-lactamases-esbls-in-critical-care-patients-from-2001-2009
#5
J Kristie Johnson, Gwen L Robinson, Lisa L Pineles, Adebola O Ajao, LiCheng Zhao, Jennifer S Albrecht, Anthony D Harris, Kerri A Thom, Jon P Furuno
Extended spectrum β-lactamase (ESBL) -producing Enterobacteriaceae are increasing in prevalence worldwide. Carbapenem antibiotics are used as a first line of therapy against ESBL-producing Enterobacteriaceae. We examined gastrointestinal colonization of carbapenem-resistant-ESBLs (CR-ESBL) among a cohort of critical care patients. In this cohort of patients, we cultured for ESBL-producing Klebsiella spp. and Escherichia coli and then performed MIC susceptibility testing for imipenem, doripenem, meropenem, and ertapenem on the patient's first isolate...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28125817/participation-of-necroptosis-in-the-host-response-to-acute-bacterial-pneumonia
#6
Danielle Ahn, Alice Prince
Common pulmonary pathogens, such as Streptococcus pneumoniae and Staphylococcus aureus, as well as the host-adapted pathogens responsible for health care-associated pneumonias, such as the carbapenem-resistant Klebsiella pneumoniae and Serratia marcecsens, are able to activate cell death through the RIPK1/RIPK3/MLKL cascade that causes necroptosis. Necroptosis can influence the pathogenesis of pneumonia through several mechanisms. Activation of this pathway can result in the loss of specific types of immune cells, especially macrophages, and, in so doing, contribute to host pathology through the loss of their critical immunoregulatory functions...
January 27, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28115349/survival-of-carbapenem-resistant-st258-klebsiella-pneumoniae-in-human-blood
#7
Frank R DeLeo, Scott D Kobayashi, Adeline R Porter, Brett Freedman, David W Dorward, Liang Chen, Barry N Kreiswirth
Klebsiella pneumoniae is a prominent cause of nosocomial infections worldwide. Bloodstream infections caused by carbapenem-resistant K. pneumoniae, including the epidemic lineage known as multilocus sequence type 258 (ST258), are difficult to treat and mortality is high. Thus, it is imperative that we gain a better understanding of host defense against this pathogen as a step toward developing novel therapies. Here we tested the hypothesis that resistance of ST258 to bactericidal components of human blood, such as serum complement, is linked to virulence capacity in the context of bacteremia...
January 23, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28103139/endotoxin-neutralization-by-an-o-antigen-specific-monoclonal-antibody-a-potential-novel-therapeutic-approach-against-klebsiella-pneumoniaest258
#8
Valéria Szijártó, Luis M Guachalla, Katharina Hartl, Cecília Varga, Adriana Badarau, Irina Mirkina, Zehra C Visram, Lukas Stulik, Christine A Power, Eszter Nagy, Gábor Nagy
Klebsiella pneumoniae ST258 is a globally distributed multi-drug resistant pathogen responsible for severe invasive infections. In this study, the different virulence potential of K. pneumoniae ST258 isolates in endotoxin susceptible versus resistant animal models was shown. Furthermore, ST258 clinical isolates were found highly sensitive to the bactericidal effect of naive animal and human serum. These observations imply that LPS, released from the rapidly lysed bacteria, may contribute to the high mortality associated with ST258 bacteremia cases...
January 19, 2017: Virulence
https://www.readbyqxmd.com/read/28096418/multi-institute-analysis-of-carbapenem-resistance-reveals-remarkable-diversity-unexplained-mechanisms-and-limited-clonal-outbreaks
#9
Gustavo C Cerqueira, Ashlee M Earl, Christoph M Ernst, Yonatan H Grad, John P Dekker, Michael Feldgarden, Sinéad B Chapman, João L Reis-Cunha, Terrance P Shea, Sarah Young, Qiandong Zeng, Mary L Delaney, Diane Kim, Ellena M Peterson, Thomas F O'Brien, Mary Jane Ferraro, David C Hooper, Susan S Huang, James E Kirby, Andrew B Onderdonk, Bruce W Birren, Deborah T Hung, Lisa A Cosimi, Jennifer R Wortman, Cheryl I Murphy, William P Hanage
Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28081233/differences-in-inflammatory-response-induced-by-two-representatives-of-clades-of-the-pandemic-st258-klebsiella-pneumoniae-clonal-lineage-producing-kpc-type-carbapenemases
#10
Giuseppe Castronovo, Ann Maria Clemente, Alberto Antonelli, Marco Maria D'Andrea, Michele Tanturli, Eloisa Perissi, Sara Paccosi, Astrid Parenti, Federico Cozzolino, Gian Maria Rossolini, Maria Gabriella Torcia
ST258-K. pneumoniae (ST258-KP) strains, the most widespread multidrug-resistant hospital-acquired pathogens, belong to at least two clades differing in a 215 Kb genomic region that includes the cluster of capsule genes. To investigate the effects of the different capsular phenotype on host-pathogen interactions, we studied representatives of ST258-KP clades, KKBO-1 and KK207-1, for their ability to activate monocytes and myeloid dendritic cells from human immune competent hosts. The two ST258-KP strains strongly induced the production of inflammatory cytokines...
2017: PloS One
https://www.readbyqxmd.com/read/28031204/chromosomal-integration-of-the-klebsiella-pneumoniae-carbapenemase-gene-blakpc-in-klebsiella-species-is-elusive-but-not-rare
#11
Amy J Mathers, Nicole Stoesser, Weidong Chai, Joanne Carroll, Katie Barry, Anita Cherunvanky, Robert Sebra, Andrew Kasarskis, Tim E Peto, A Sarah Walker, Costi D Sifri, Derrick W Crook, Anna E Sheppard
Carbapenemase genes in Enterobacteriaceae are mostly described as being plasmid associated. However, the genetic context of carbapenemase genes is not always confirmed in epidemiological surveys, and the frequency of their chromosomal integration therefore is unknown. A previously sequenced collection of blaKPC-positive Enterobacteriaceae from a single U.S. institution (2007 to 2012; n = 281 isolates from 182 patients) was analyzed to identify chromosomal insertions of Tn4401, the transposon most frequently harboring blaKPC Using a combination of short- and long-read sequencing, we confirmed five independent chromosomal integration events from 6/182 (3%) patients, corresponding to 15/281 (5%) isolates...
March 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27777978/acquired-resistance-to-innate-immune-clearance-promotes-klebsiella-pneumoniae-st258-pulmonary-infection
#12
Danielle Ahn, Hernán Peñaloza, Zheng Wang, Matthew Wickersham, Dane Parker, Purvi Patel, Antonius Koller, Emily I Chen, Susan M Bueno, Anne-Catrin Uhlemann, Alice Prince
Adaptive changes in the genome of a locally predominant clinical isolate of the multidrug-resistant Klebsiella pneumoniae ST258 (KP35) were identified and help to explain the selection of this strain as a successful pulmonary pathogen. The acquisition of 4 new ortholog groups, including an arginine transporter, enabled KP35 to outcompete related ST258 strains lacking these genes. KP35 infection elicited a monocytic response, dominated by Ly6C(hi) monocytic myeloid-derived suppressor cells that lacked phagocytic capabilities, expressed IL-10, arginase, and antiinflammatory surface markers...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27683817/cd36-provides-host-protection-against-klebsiella-pneumoniae-intrapulmonary-infection-by-enhancing-lipopolysaccharide-responsiveness-and-macrophage-phagocytosis
#13
Tolani F Olonisakin, Huihua Li, Zeyu Xiong, Elizabeth J K Kochman, Minting Yu, Yanyan Qu, Mei Hulver, Jay K Kolls, Claudette St Croix, Yohei Doi, Minh-Hong Nguyen, Robert M Q Shanks, Rama K Mallampalli, Valerian E Kagan, Anuradha Ray, Roy L Silverstein, Prabir Ray, Janet S Lee
Klebsiella pneumoniae remains an important cause of intrapulmonary infection and invasive disease worldwide. K. pneumoniae can evade serum killing and phagocytosis primarily through the expression of a polysaccharide capsule, but its pathogenicity is also influenced by host factors. We examined whether CD36, a scavenger receptor that recognizes pathogen and modified self ligands, is a host determinant of K. pneumoniae pathogenicity. Despite differences in serum sensitivity and virulence of 3 distinct K. pneumoniae (hypermucoviscous K1, research K2, and carbapenemase-producing ST258) strains, the absence of CD36 significantly increased host susceptibility to acute intrapulmonary infection by K...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27617554/a-new-case-report-of-urinary-tract-infection-due-to-kpc-3-producing-klebsiella-pneumoniae-st258-in-spain
#14
A Sorlózano-Puerto, D Esteva-Fernández, J Oteo-Iglesias, J M Navarro-Marí, J Gutiérrez-Fernández
OBJECTIVE: We describe the characterization of a new isolated in Spain of Klebsiella pneumoniae ST258 producing KPC-3, carbapenems non-susceptible, recovered from a sample of urine from a patient with urinary tract infection and no history of carbapenems exposure. METHODS: After the isolation, identification of K. pneumoniae was performed by biochemical tests and mass spectrometry. The carbapenems susceptibility testing was performed by microdilution and E-test in cation-adjusted Mueller-Hinton...
September 2016: Archivos Españoles de Urología
https://www.readbyqxmd.com/read/27585968/molecular-epidemiology-of-kpc-producing-klebsiella-pneumoniae-from-invasive-infections-in-italy-increasing-diversity-with-predominance-of-the-st512-clade-ii-sublineage
#15
Viola Conte, Monica Monaco, Tommaso Giani, Fortunato D'Ancona, Maria Luisa Moro, Fabio Arena, Marco Maria D'Andrea, Gian Maria Rossolini, Annalisa Pantosti
OBJECTIVES: The spread of carbapenem-resistant Enterobacteriaceae (CRE) represents one of the most worrisome problems for clinical medicine worldwide. In Italy, the Antibiotic-Resistance-Istituto Superiore di Sanità surveillance network, in collaboration with the Committee for Antimicrobial Agents of the Italian Society of Clinical Microbiologists, promoted a study to investigate the carbapenem-resistance mechanisms, clonal relatedness and capsular typing of a recent collection of carbapenem-resistant Klebsiella pneumoniae (CR-KP)...
September 1, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27530831/ctx-m-15-in-combination-with-aac-6-ib-cr-is-the-most-prevalent-mechanism-of-resistance-both-in-escherichia-coli-and-klebsiella-pneumoniae-including-k-pneumoniae-st258-in-an-icu-in-uruguay
#16
Inés Bado, Claudia Gutiérrez, Virginia García-Fulgueiras, Nicolás F Cordeiro, Lucía Araújo Pirez, Verónica Seija, Cristina Bazet, Gloria Rieppi, Rafael Vignoli
The objectives of this study were (i) to determine the extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EcKp) clones circulating in an intensive care unit (ICU) in Uruguay between August 2010 and July 2011, (ii) to characterise the ESBL and plasmid-mediated quinolone resistance (PMQR) genes of the studied isolates and (iii) to determine the virulotype of the clinical isolates. Clinical and gut-colonising ESBL-EcKp from ICU patients were studied. Bacterial identification and antibiotic susceptibility determination were performed using a VITEK(®)2 system...
September 2016: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/27379038/global-dissemination-of-carbapenemase-producing-klebsiella-pneumoniae-epidemiology-genetic-context-treatment-options-and-detection-methods
#17
REVIEW
Chang-Ro Lee, Jung Hun Lee, Kwang Seung Park, Young Bae Kim, Byeong Chul Jeong, Sang Hee Lee
The emergence of carbapenem-resistant Gram-negative pathogens poses a serious threat to public health worldwide. In particular, the increasing prevalence of carbapenem-resistant Klebsiella pneumoniae is a major source of concern. K. pneumoniae carbapenemases (KPCs) and carbapenemases of the oxacillinase-48 (OXA-48) type have been reported worldwide. New Delhi metallo-β-lactamase (NDM) carbapenemases were originally identified in Sweden in 2008 and have spread worldwide rapidly. In this review, we summarize the epidemiology of K...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27357502/high-genotypic-diversity-among-methicillin-resistant-staphylococcus-pseudintermedius-isolated-from-canine-infections-in-denmark
#18
Peter Damborg, Arshnee Moodley, Bent Aalbæk, Gianpiero Ventrella, Teresa Pires Dos Santos, Luca Guardabassi
BACKGROUND: Methicillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged globally in companion animals in the last decade. In Europe, the multidrug-resistant sequence type (ST)71 is widespread, but recently other clones have appeared. The objective of this study was to examine genotypic diversity and antimicrobial resistance of clinical MRSP isolates obtained from dogs, including dogs sampled on multiple occasions, in Denmark over a six-year period. For that purpose a total of 46 clinical MRSP isolates obtained from 36 dogs between 2009 and 2014 were subjected to antimicrobial susceptibility testing, multilocus-sequence typing (MLST) and SCCmec typing...
June 29, 2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27334661/characterization-of-kpc-encoding-plasmids-from-two-endemic-settings-greece-and-italy
#19
Costas C Papagiannitsis, Vincenzo Di Pilato, Tommaso Giani, Panagiota Giakkoupi, Eleonora Riccobono, Giulia Landini, Vivi Miriagou, Alkiviadis C Vatopoulos, Gian Maria Rossolini
OBJECTIVES: Global dissemination of KPC-type carbapenemases is mainly associated with the spread of high-risk clones of Klebsiella pneumoniae and of KPC-encoding plasmids. In this study, we explored the population structure of KPC-encoding plasmids from the recent epidemics of KPC-producing K. pneumoniae (KPC-Kp) in Greece and Italy, the two major European endemic settings. METHODS: Thirty-four non-replicate clinical strains of KPC-Kp representative of the early phases (2008-11) of the Greek (n = 22) and Italian (n = 12) epidemics were studied...
October 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27261267/glutathione-s-transferase-fosa6-of-klebsiella-pneumoniae-origin-conferring-fosfomycin-resistance-in-esbl-producing-escherichia-coli
#20
Qinglan Guo, Adam D Tomich, Christi L McElheny, Vaughn S Cooper, Nicole Stoesser, Minggui Wang, Nicolas Sluis-Cremer, Yohei Doi
OBJECTIVES: The objectives of this study were to elucidate the genetic context of a novel plasmid-mediated fosA variant, fosA6, conferring fosfomycin resistance and to characterize the kinetic properties of FosA6. METHODS: The genome of fosfomycin-resistant Escherichia coli strain YD786 was sequenced. Homologues of FosA6 were identified through BLAST searches. FosA6 and FosA(ST258) were purified and characterized using a steady-state kinetic approach. Inhibition of FosA activity was examined with sodium phosphonoformate...
September 2016: Journal of Antimicrobial Chemotherapy
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