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https://www.readbyqxmd.com/read/28739787/resistance-to-ceftazidime-avibactam-is-due-to-transposition-of-kpc-in-a-porin-deficient-strain-of-klebsiella-pneumoniae-with-increased-efflux-activity
#1
Kirk Nelson, Peera Hemarajata, Dongxu Sun, Debora Rubio-Aparicio, Ruslan Tsivkovski, Shangxin Yang, Robert Sebra, Andrew Kasarskis, Hoan Nguyen, Blake M Hanson, Shana Leopold, George Weinstock, Olga Lomovskaya, Romney M Humphries
Ceftazidime-avibactam is an antibiotic with activity against serine beta-lactamases, including KPC. Recently, reports have emerged of KPC-producing isolates resistant to this antibiotic, including a report of a wild-type KPC-3 producing sequence type 258 Klebsiella pneumoniae that was resistant to ceftazidime-avibactam. We describe a detailed analysis of this isolate, in the context of two other closely related KPC-3 producing isolates, recovered from the same patient. Both isolates encoded a non-functional OmpK35, whereas we demonstrate a novel T333N mutation in OmpK36, present in the ceftazidime-avibactam resistant isolate, reduced activity of this porin and impacted ceftazidime-avibactam susceptibility...
July 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28731269/biofilm-formation-and-antibiotic-resistance-in-klebsiella-pneumoniae-urinary-strains
#2
Claudia Vuotto, Francesca Longo, Chiara Pascolini, Gianfranco Donelli, Maria Pia Balice, Maria Francesca Libori, Valentina Tiracchia, Antonino Salvia, Pietro Emanuele Varaldo
AIMS: Multi-drug resistant Klebsiella pneumoniae has become a relevant healthcare-associated pathogen. Capsule, type 1 and 3 fimbriae (mrkA gene), type 2 quorum-sensing system (luxS), synthesis of D-galactan I (wbbM), LPS transport (wzm) and poly-beta-1,6-N-acetyl-D-glucosamine (pgaA) seem involved in K. pneumoniae biofilm. Non-enzymatic antibiotic resistance is related to non-expression or mutation of porins (OmpK35 and OmpK36), and efflux pump (acrB) over-expression. The aim of this study was to analyse some virulence factors of K...
July 21, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28713357/extensively-drug-resistant-klebsiella-pneumoniae-causing-nosocomial-bloodstream-infections-in-china-molecular-investigation-of-antibiotic-resistance-determinants-informing-therapy-and-clinical-outcomes
#3
Wenzi Bi, Haiyang Liu, Rhys A Dunstan, Bin Li, Von Vergel L Torres, Jianming Cao, Lijiang Chen, Jonathan J Wilksch, Richard A Strugnell, Trevor Lithgow, Tieli Zhou
The rise in diversity of antimicrobial resistance phenotypes seen in Klebsiella pneumoniae is becoming a serious antibiotic management problem. We sought to investigate the molecular characteristics and clinical implications of extensively drug-resistant (XDR) K. pneumoniae isolated from different nosocomial bloodstream infections (BSIs) patients from July 2013 to November 2015. Even in combination treatment, meropenem did not protect against mortality of BSIs patients (P = 0.015). In contrast, tigecycline in combination with other antimicrobial agents significantly protected against mortality (P = 0...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28708586/whole-genome-and-transcriptome-analysis-reveal-maldi-tof-ms-and-sds-page-have-limited-performance-for-the-detection-of-the-key-outer-membrane-protein-in-carbapenem-resistant-klebsiella-pneumoniae-isolates
#4
Naina Adren Pinto, Roshan D'Souza, In Sik Hwang, Jongrak Choi, Yong Ha In, Hyung Soon Park, Choong-Min Ryu, Dongeun Yong, Kyungwon Lee
To detect the outer membrane protein (OMP), which plays a key role in carbapenem resistance, whole-genome and transcriptome analysis of the clinical carbapenem-resistant Klebsiella pneumoniae was carried out. The index strain lacked both OmpK35 and OmpK36, whereas the other strains lacked only OmpK35. After SDS-PAGE, the putative OMP bands were excised and identified as OmpA and OmpK36. MALDI-TOF MS showed peaks at ~36 and ~38 kDa that corresponded to OmpA and OmpK36, respectively. In all the strains except YMC2014/03/P345, the ~38 kDa peaks were present...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28630202/identifying-spectra-of-activity-and-therapeutic-niches-for-ceftazidime-avibactam-and-imipenem-relebactam-against-carbapenem-resistant-enterobacteriaceae
#5
Ghady Haidar, Cornelius J Clancy, Liang Chen, Palash Samanta, Ryan K Shields, Barry N Kreiswirth, M Hong Nguyen
We determined imipenem, imipenem-relebactam, ceftazidime and ceftazidime-avibactam minimum inhibitory concentrations (MICs) against 100 CRE isolates that underwent whole genome sequencing. KPCs were the most common carbapenemases. Forty-six isolates carried ESBLs. With the addition of relebactam, imipenem susceptibility increased from 8% to 88%. With the addition of avibactam, ceftazidime susceptibility increased from 0% to 85%. Neither imipenem-relebactam nor ceftazidime-avibactam was active against MBL-producers...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28590820/activity-of-ceftazidime-avibactam-against-clinical-isolates-of-klebsiella-pneumoniae-including-kpc-carrying-isolates-endemic-to-new-york-city
#6
Nyla Manning, Gregory Balabanian, Michael Rose, David Landman, John Quale
In this report, we examined the (1) activity of ceftazidime-avibactam against clinical isolates Klebsiella pneumoniae, including those harboring blaKPC, (2) potential mechanisms leading to reduced susceptibility, and (3) activity of ceftazidime-avibactam when combined with other agents. Of 802 carbapenem-resistant isolates of K. pneumoniae gathered from New York City from 1999 to 2014, all were susceptible to ceftazidime-avibactam. Minimum inhibitory concentrations (MICs) were higher in isolates with K. pneumoniae, with the carbapenemase (KPC)-3 (compared to KPC-2), and those with a frameshift mutation in ompK35...
June 7, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28402509/identification-of-is1r-and-is10r-elements-inserted-into-ompk36-porin-gene-of-two-multidrug-resistant-klebsiella-pneumoniae-hospital-strains
#7
Anastasia I Lev, Evgeny I Astashkin, Rima Z Shaikhutdinova, Mikhail E Platonov, Nikolay N Kartsev, Nikolay V Volozhantsev, Olga N Ershova, Edward A Svetoch, Nadezhda K Fursova
Hospital Klebsiella pneumoniae strains (n = 196) were collected in 2012-16 from the patients of a Moscow neurosurgical intensive care unit. Klebsiella pneumoniae strains were multidrug-resistant and carried beta-lactamase genes blaSHV (97.4% of strains), blaCTX-M (84.7%), blaTEM (56.1%), blaOXA-48-like (49.0%) and blaNDM-1 (one strain), class 1 integrons (43.4% of strains) and porin protein ompK36 gene (100% of strains). The ompK36 porin protein gene disruption by insertion sequence (IS) elements and OmpK36 production loss in two strains were detected in this study...
May 1, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28333323/high-ceftazidime-hydrolysis-activity-and-porin-ompk35-deficiency-contribute-to-the-decreased-susceptibility-to-ceftazidime-avibactam-in-kpc-producing-klebsiella-pneumoniae
#8
Zhen Shen, Baixing Ding, Meiping Ye, Peng Wang, Yingmin Bi, Shi Wu, Xiaogang Xu, Qinglan Guo, Minggui Wang
Objectives: To investigate mechanisms for the decreased susceptibility to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae (KPC-KP). Methods: A total of 24 isolates, 8 each with ceftazidime/avibactam MICs of 4-8, 1-2 and ≤0.5 mg/L, were randomly selected from 214 clinical isolates of KPC-KP, and the β-lactamase hydrolysis activity and porin expression profiles were determined. Plasmid profile and relative expression and copy number of the bla KPC gene were also analysed...
March 15, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28242667/in-vitro-selection-of-meropenem-resistance-among-ceftazidime-avibactam-resistant-meropenem-susceptible-klebsiella-pneumoniae-isolates-with-variant-kpc-3-carbapenemases
#9
Ryan K Shields, M Hong Nguyen, Ellen G Press, Liang Chen, Barry N Kreiswirth, Cornelius J Clancy
Ceftazidime-avibactam resistance is mediated by blaKPC-3 mutations, which restore carbapenem susceptibility. We subjected Klebsiella pneumoniae isolates with different blaKPC-3 mutations (n = 5) or wild-type blaKPC-3 (n = 2) to serial passages with meropenem. The meropenem MIC against each isolate increased. Mutations in the ompK36 porin gene evolved in 5 isolates. Among isolates with D179Y substitutions in KPC-3, blaKPC-3 mutations reverted to wild type, were replaced by new mutations, or were retained. Carbapenem treatment of ceftazidime-avibactam-resistant K...
May 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28031200/low-frequency-of-ceftazidime-avibactam-resistance-among-enterobacteriaceae-isolates-carrying-blakpc-collected-in-u-s-hospitals-from-2012-to-2015
#10
Mariana Castanheira, Rodrigo E Mendes, Helio S Sader
Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae isolates have been increasingly reported worldwide, and therapeutic options to treat infections caused by these organisms are limited. We evaluated the activity of ceftazidime-avibactam and comparators against 456 Enterobacteriaceae isolates carrying blaKPC collected from 79 U.S. hospitals during 2012 to 2015. Overall, ceftazidime-avibactam (MIC50/90, 0.5/2 μg/ml; 99.3% susceptible) and tigecycline (MIC50/90, 0.5/1 μg/ml; 98.9% susceptible at ≤2 μg/ml) were the most active agents...
March 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27788691/outbreak-of-kpc-3-producing-st15-and-st348-klebsiella-pneumoniae-in-a-portuguese-hospital
#11
D Vubil, R Figueiredo, T Reis, C Canha, L Boaventura, G J DA Silva
To date, only a few sporadic cases of infections due to Klebsiella pneumoniae carbapenemase (KPC) producers have been reported in Portugal. Here, we report for the first time an outbreak of K. pneumoniae KPC-3 producers in a tertiary-care hospital during 2013. Twenty-seven ertapenem-resistant K. pneumoniae were identified in patients at a tertiary-care hospital during 2013 isolated predominantly from urine (48·1%) and blood (25·9%) cultures. All isolates were highly resistant to β-lactam antibiotics and most showed intermediate resistance to imipenem...
February 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/27645385/klebsiella-pneumoniae-major-porins-ompk35-and-ompk36-allow-more-efficient-diffusion-of-%C3%AE-lactams-than-their-escherichia-coli-homologs-ompf-and-ompc
#12
Etsuko Sugawara, Seiji Kojima, Hiroshi Nikaido
Klebsiella pneumoniae, one of the most important nosocomial pathogens, is becoming a major problem in health care because of its resistance to multiple antibiotics, including cephalosporins of the latest generation and, more recently, even carbapenems. This is largely due to the spread of plasmid-encoded extended-spectrum β-lactamases. However, antimicrobial agents must first penetrate the outer membrane barrier in order to reach their targets, and hydrophilic and charged β-lactams presumably diffuse through the porin channels...
December 1, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27542822/molecular-epidemiology-of-extensively-drug-resistant-klebsiella-pneumoniae-outbreak-in-wenzhou-southern-china
#13
Jia Du, Jianming Cao, Lizhen Shen, Wenzi Bi, Xiaoxiao Zhang, Haiyang Liu, Hong Lu, Tieli Zhou
The emergence of extensively drug-resistant (XDR) Klebsiella pneumoniae has become a major challenge worldwide. In this study, we characterized the phenotypes and genetic features of nine XDR K. pneumoniae isolates from an integrated hospital in Zhejiang province, China, from September to October 2014. These XDR K. pneumoniae possessed at least five resistance determinants which contribute to highly resistant to β-lactam, β-lactam/inhibitor combinations, aminoglycosides, quinolones, carbapenems, chloroamphenicol and fosfomycin...
October 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27216068/frequency-of-bkc-1-producing-klebsiella-species-isolates
#14
Willames M B S Martins, Adriana G Nicoletti, Silvia R Santos, Jorge L M Sampaio, Ana C Gales
BKC-1 is a new class A serine carbapenemase that was recently identified in Klebsiella pneumoniae clinical isolates. The principal objective of this study was to evaluate the frequency of blaBKC-1 by testing a collection of Klebsiella isolates. Only 2 of 635 Klebsiella isolates (0.3%) carried blaBKC-1 The two BKC-1-producing isolates belonged to clonal complex 442 and possessed identical pulsed-field gel electrophoresis patterns. The blaBKC-1 gene was inserted into a 10-kb plasmid that was identical to the previously reported plasmid, p60136...
August 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27206024/molecular-epidemiology-of-carbapenem-resistant-klebsiella-pneumoniae-in-greece
#15
REVIEW
Theodoros Karampatakis, Charalampos Antachopoulos, Elias Iosifidis, Athanassios Tsakris, Emmanuel Roilides
Hospital infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) constitute a worldwide problem associated with high rates of treatment failure and mortality. In Greece, CRKP have emerged in 2002 due to VIM carbapenemase production and later due to KPC, NDM and OXA-48-like carbapenemases that have become endemic. The molecular epidemiology of CRKP strains is dynamic, as antibiotic consumption and worldwide traveling are strongly associated with global spread of CRKP isolates. Lately, porin defects, such as disruption of OmpK35 and production of OmpK36 variant, have also contributed to carbapenem resistance...
June 2016: Future Microbiology
https://www.readbyqxmd.com/read/27041106/high-level-carbapenem-resistant-oxa-48-producing-klebsiella-pneumoniae-with-a-novel-ompk36-variant-and-low-level-carbapenem-resistant-non-porin-deficient-oxa-181-producing-escherichia-coli-from-thailand
#16
Kamonwan Lunha, Aroonwadee Chanawong, Aroonlug Lulitanond, Chotechana Wilailuckana, Nicha Charoensri, Lumyai Wonglakorn, Pimjai Saenjamla, Prajuab Chaimanee, Sunpetch Angkititrakul, Ploenchan Chetchotisakd
Five blaOXA-48-like-carrying Enterobacteriaceae isolates collected from two Thai patients in December 2012 were characterized. Three Klebsiella pneumoniae isolates giving two different pulsed-field gel electrophoresis patterns and sequence types (ST11 and ST37) from patient 1 harbored blaOXA-48 locating on Tn1999.2, whereas two Escherichia coli isolates with the same pulsotype and ST5 from Patient 2 carried ISEcp1-associated blaOXA-181. One K. pneumoniae strain had blaSHV-12, blaDHA-1, qnrB, and qnrS, while another strain harbored blaCTX-M-15, qnrS and aac(6')-Ib-cr...
June 2016: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/27002853/risk-factors-for-kpc-producing-klebsiella-pneumoniae-watch-out-for-surgery
#17
Kesia Esther da Silva, Wirlaine Glauce Maciel, Flávia Patussi Correia Sacchi, Cecilia Godoy Carvalhaes, Fernanda Rodrigues-Costa, Ana Carolina Ramos da Silva, Mariana Garcia Croda, Fábio Juliano Negrão, Julio Croda, Ana Cristina Gales, Simone Simionatto
This study describes the molecular characteristics and risk factors associated with carbapenem-resistant Klebsiella pneumoniae strains. Risk factors associated with KPC-producing K. pneumoniae strains were investigated in this case-control study from May 2011 to May 2013. Bacterial identification was performed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined by broth microdilution. Carbapenemase production was assessed by both modified Hodge test (MHT) and ertapenem hydrolysis using MALDI-TOF MS...
June 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/26912748/predictability-of-phenotype-in-relation-to-common-%C3%AE-lactam-resistance-mechanisms-in-escherichia-coli-and-klebsiella-pneumoniae
#18
Alex Agyekum, Alicia Fajardo-Lubián, Xiaoman Ai, Andrew N Ginn, Zhiyong Zong, Xuejun Guo, John Turnidge, Sally R Partridge, Jonathan R Iredell
The minimal concentration of antibiotic required to inhibit the growth of different isolates of a given species with no acquired resistance mechanisms has a normal distribution. We have previously shown that the presence or absence of transmissible antibiotic resistance genes has excellent predictive power for phenotype. In this study, we analyzed the distribution of six β-lactam antibiotic susceptibility phenotypes associated with commonly acquired resistance genes in Enterobacteriaceae in Sydney, Australia...
May 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/26872343/whole-genome-sequence-of-klebsiella-pneumoniae-u25-a-hypermucoviscous-multidrug-resistant-biofilm-producing-isolate-from-india
#19
Zumaana Rafiq, Nithin Sam, Rama Vaidyanathan
Klebsiella pneumoniae U25 is a multidrug resistant strain isolated from a tertiary care hospital in Chennai, India. Here, we report the complete annotated genome sequence of strain U25 obtained using PacBio RSII. This is the first report of the whole genome of K. pneumoniaespecies from Chennai. It consists of a single circular chromosome of size 5,491,870-bp and two plasmids of size 211,813 and 172,619-bp. The genes associated with multidrug resistance were identified. The chromosome of U25 was found to have eight antibiotic resistant genes [blaOXA-1,blaSHV-28, aac(6')1b-cr,catB3, oqxAB, dfrA1]...
February 2016: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/26407326/genetic-characterization-of-carbapenem-resistant-enterobacteriaceae-and-the-spread-of-carbapenem-resistant-klebsiella-pneumonia-st340-at-a-university-hospital-in-thailand
#20
Thidarat Netikul, Pattarachai Kiratisin
Carbapenem-resistant Enterobacteriaceae (CRE) has increasingly spread worldwide in the past decade. The prevalence and characteristics of CRE in Thailand are unknown. In this study, we conducted a 2-year surveillance of CRE among 12,741 clinical isolates of Enterobacteriaceae at the largest university hospital in Thailand with molecular characterization of beta-lactamase (bla) genes, including carbapenemase genes. The CRE prevalence was 1.4%. blaKPC-13 and blaIMP-14a were the only carbapenemase genes detected among these CRE isolates...
2015: PloS One
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