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kpc treatment

Xingyu Zhang, Di Chen, Guifeng Xu, Weichun Huang, Xing Wang
Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center...
2018: PloS One
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
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
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
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
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
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
Jesús Rodríguez-Baño, Belén Gutiérrez-Gutiérrez, Isabel Machuca, Alvaro Pascual
Therapy of invasive infections due to multidrug-resistant Enterobacteriaceae (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole...
April 2018: Clinical Microbiology Reviews
Sarah Christina Jane Jorgensen, Michael Joseph Rybak
Vaborbactam (VAB; formerly RPX7009) is a novel beta-lactamase inhibitor based on a cyclic boronic acid pharmacophore with potent inhibitory activity against Ambler class A and C beta-lactamases. It has been co-formulated with meropenem to restore its activity against Klebsiella pneumoniae carbapenemases (KPC). VAB does not inhibit class B or D carbapenemases, nor does it improve the activity of meropenem against multidrug-resistant non-fermenting Gram-negative bacilli, notably Acinetobacter spp. and Pseudomonas aeruginosa...
February 10, 2018: Pharmacotherapy
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
Yi Li, Qiao-Ling Sun, Yingbo Shen, Yangjunna Zhang, Jun-Wen Yang, Ling-Bin Shu, Hong-Wei Zhou, Yang Wang, Bing Wang, Rong Zhang, Shaolin Wang, Zhangqi Shen
The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance gene mcr-1 amongst CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014--2016, a total of 7,249 Enterobacteriaceae isolates were collected from clinical samples, among which 18...
January 31, 2018: Journal of Clinical Microbiology
María García-Castillo, Sergio García-Fernández, Rosa Gómez-Gil, Cristina Pitart, Marina Oviaño, Irene Gracia-Ahufinger, Jazmín Díaz-Regañón, Marta Tato, Rafael Cantón
The increasing rates of carbapenemase-producing Enterobacteriaceae (CPE) represent an important threat to health care systems and make treatment of CPE infections a challenge. The aim of the infection-carbapenem resistance evaluation surveillance trial (iCREST) was to determinate the prevalence of CPE in urine specimens in Spain and to evaluate the in vitro activity of ceftazidime-avibactam. Urine specimens (n=11,826) were included and activity of ceftazidime-avibactam and comparators were investigated by broth microdilution in CPE...
January 22, 2018: International Journal of Antimicrobial Agents
Hao Xu, Xin Wang, Xiao Yu, Jing Zhang, Lihua Guo, Chen Huang, Xiawei Jiang, Xuewen Li, Youjun Feng, Beiwen Zheng
The wide spread of carbapenemase-producing Enterobacteriaceae (CPE) in the environment is an emerging environmental issue with potentially-serious public health implications. However, carbapenemase-producing Citrobacter from environment has rarely been investigated. Here we report the isolation and comparative genomics of carbapenemase-producing Citrobacter isolates from river sediment in China. Potential CPE was isolated by selective MacConkey agar plates containing 2 mg/L meropenem. The presence of carbapenemase genes was detected by PCR and sequencing...
January 19, 2018: Environmental Pollution
Novella Carannante, Carlo Pallotto, Mariano Bernardo, Giovanni Di Caprio, Carlo Tascini
KPC-producing Klebsiella pneumoniae (KPC-Kp) is nowadays a global concern. Ceftazidime/avibactam is the most promising novel antibiotic combination available at the moment. We describe the case of a migrant with no risk factors for an infection due to multidrug resistant bacteria. He suffered from a KPC-Kp cellulitis and was treated with a ceftazidime/avibactam-meropenem-fosfomycin combination that not only eradicated the infection but also decontaminated his gut. Ceftazidime/avibactam-based treatment can be useful also in decontamination procedures...
January 16, 2018: Journal of Chemotherapy
Kyoichi Saito, Shiro Endo, Makoto Katsumi, Chiyuki Ishizawa, Yuko Fujikawa, Shinya Inomata, Masahiro Toyokawa, Mitsuo Kaku
  The FilmArray (FA) is a multiplex polymerase chain reaction (PCR)-based desktop microbial detection system. The Blood Culture Identification (BCID) panel is an adaptable panel for the FA, which diagnoses sepsis or/and systemic infections by detecting 14 bacterial species, 4 bacterial genera, 1 bacterial family, 5 yeast species, and 3 antimicrobial resistance genes (mecA, KPC, and vanA/B) from positive blood cultures within 1 hour. We retrospectively evaluated the FA-BCID panel, using 54 positive blood cultures, from which 57 bacteria and 3 yeasts were identified through matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis...
December 26, 2017: Japanese Journal of Infectious Diseases
Patricia Dauer, Xianda Zhao, Vineet K Gupta, Nikita S Sharma, Kousik Kesh, Prisca Gnamlin, Vikas Dudeja, Selwyn M Vickers, Sulagna Banerjee, Ashok Saluja
Resident fibroblasts that contact tumor epithelial cells (TEC) can become irreversibly activated as cancer-associated-fibroblasts (CAF) which stimulate oncogenic signaling in TEC. In this study, we evaluated the crosstalk between CAF and TEC isolated from tumors generated in a mouse model of KRAS/mutp53-induced pancreatic cancer (KPC mice). Transcriptomic profiling conducted after treatment with the anticancer compound Minnelide revealed deregulation of the TGF-β signaling pathway in CAF, resulting in an apparent reversal of their activated state to a quiescent, non-proliferative state...
December 19, 2017: Cancer Research
Xinxin Song, Shan Zhu, Yangchun Xie, Jiao Liu, Lingyi Sun, Dexing Zeng, Pengcheng Wang, Xiaochao Ma, Guido Kroemer, David L Bartlett, Timothy R Billiar, Michael Lotze, Herbert Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Maintenance of acid-base homeostasis is required for normal physiology, metabolism, and development. It is not clear how cell death is activated in response to changes in pH. We performed a screen to identify agents that induce cell death in a pH-dependent manner (we call this alkaliptosis) in pancreatic ductal adenocarcinoma cancer (PDAC) cells and tested their effects in mice. METHODS: We screened a library of 254 compounds that interact with G protein-coupled receptors (GPCRs) to identify those with cytotoxic activity against a human PDAC cell line (PANC1)...
December 14, 2017: Gastroenterology
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