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https://www.readbyqxmd.com/read/29444952/treatment-of-infections-caused-by-extended-spectrum-beta-lactamase-ampc-and-carbapenemase-producing-enterobacteriaceae
#1
REVIEW
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
https://www.readbyqxmd.com/read/29427523/meropenem-and-vaborbactam-stepping-up-the-battle-against-carbapenem-resistant-enterobacteriaceae
#2
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
https://www.readbyqxmd.com/read/29424684/genome-analysis-of-clinical-multilocus-sequence-type-11-klebsiella-pneumoniae-from-china
#3
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
https://www.readbyqxmd.com/read/29386265/rapid-increase-in-the-prevalence-of-carbapenem-resistant-enterobacteriaceae-cre-and-emergence-of-colistin-resistance-gene-mcr-1-in-cre-in-a-hospital-in-henan-china
#4
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
https://www.readbyqxmd.com/read/29371104/activity-of-ceftazidime-avibactam-against-carbapenemase-producing-enterobacteriaceae-from-urine-samples-obtained-during-the-infection-carbapenem-resistance-evaluation-surveillance-trial-icrest-in-spain
#5
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
https://www.readbyqxmd.com/read/29358148/first-detection-and-genomics-analysis-of-kpc-2-producing-citrobacter-isolates-from-river-sediments
#6
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
https://www.readbyqxmd.com/read/29336224/treatment-of-a-klebsiella-pneumoniae-kpc-cellulitis-and-gut-decolonization-with-ceftazidime-avibactam-in-a-migrant-from-libya
#7
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
https://www.readbyqxmd.com/read/29279453/evaluation-of-the-filmarray-blood-culture-identification-panel-in-detecting-pathogenic-microorganisms-from-positive-blood-cultures-the-first-clinical-report-in-japan
#8
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
https://www.readbyqxmd.com/read/29259015/inactivation-of-cancer-associated-fibroblasts-caf-disrupts-oncogenic-signaling-in-pancreatic-cancer-cells-and-promotes-its-regression
#9
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
https://www.readbyqxmd.com/read/29248440/jtc801-induces-ph-dependent-death-specifically-in-cancer-cells-and-slows-growth-of-tumors-in-mice
#10
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
https://www.readbyqxmd.com/read/29232103/game-changers-new-%C3%AE-lactamase-inhibitor-combinations-targeting-antibiotic-resistance-in-gram-negative-bacteria
#11
Karen Bush
Recent regulatory approvals for the β-lactam inhibitor combinations of ceftazidime-avibactam and meropenem-vaborbactam have provided two novel therapeutic options for the treatment of multidrug-resistant infections caused by Gram-negative bacteria. Most importantly, these combination agents have satisfied an important medical need related to antibiotic-resistant Klebsiella pneumoniae that produce serine carbapenemases, especially the Klebsiella pneumoniae carbapenemase (KPC) enzymes. Both combinations contain non-β-lactam β-lactamase inhibitors of novel chemical classes not previously developed as antibacterial agents, the diazabicyclooctanes and cyclic boronic acid derivatives...
December 12, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29230684/imipenem-relebactam-and-meropenem-vaborbactam-two-novel-carbapenem-%C3%AE-lactamase-inhibitor-combinations
#12
REVIEW
George G Zhanel, Courtney K Lawrence, Heather Adam, Frank Schweizer, Sheryl Zelenitsky, Michael Zhanel, Philippe R S Lagacé-Wiens, Andrew Walkty, Andrew Denisuik, Alyssa Golden, Alfred S Gin, Daryl J Hoban, Joseph P Lynch, James A Karlowsky
Relebactam (formerly known as MK-7655) is a non-β-lactam, bicyclic diazabicyclooctane, β-lactamase inhibitor that is structurally related to avibactam, differing by the addition of a piperidine ring to the 2-position carbonyl group. Vaborbactam (formerly known as RPX7009) is a non-β-lactam, cyclic, boronic acid-based, β-lactamase inhibitor. The structure of vaborbactam is unlike any other currently marketed β-lactamase inhibitor. Both inhibitors display activity against Ambler class A [including extended-spectrum β-lactamases (ESBLs), Klebsiella pneumoniae carbapenemases (KPCs)] and class C β-lactamases (AmpC)...
December 12, 2017: Drugs
https://www.readbyqxmd.com/read/29216954/-advances-in-risk-factors-of-klebsiella-pneumoniae-carbapenemases-producing-klebsiella-pneumoniae-infection-or-colonization-and-its-treatment-strategies
#13
Liang Wu, Jiawei Ying, Zhenhong Jiang, Shu Lei, Jiannong Wu, Dandan Feng, Lingcong Wang
Klebsiella pneumoniae carbapenemases-producing Klebsiella pneumoniae (KPC-Kp) has caused a global public health crisis, and the severity of its infection is associated with high mortality in hospitalized patients. Therefore, the KPC-Kp prevention methods and the corresponding treatment strategy exploration are imminent. The risk factors and the treatment progress of KPC-Kp colonization or infection are reviewed in this paper to explore corresponding preventive measures and treatment strategies for clinical prevention and treatment...
December 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/29203494/polymyxin-b-and-zti-01-fosfomycin-for-injection-against-kpc-producing-klebsiella-pneumoniae-evaluation-of-activity-and-emergence-of-resistance
#14
John K Diep, Rajnikant Sharma, Evelyn J Ellis-Grosse, Cely S Abboud, Gauri G Rao
ZTI-01 (fosfomycin for injection) is a broad spectrum antibiotic with a novel mechanism of action and is currently under development in the USA for treatment of complicated urinary tract infections. Globally, fosfomycin and polymyxin B are increasingly being used to treat multi-drug resistant Gram-negative infections. The objectives were to evaluate the pharmacodynamic activity of polymyxin B and fosfomycin alone and in combination against KPC-producing K. pneumoniae and to assess the rate and extent of emergence of resistance to different antibiotic regimens...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29186402/in-vitro-and-in-vivo-activity-of-single-and-dual-antimicrobial-agents-against-kpc-producing-klebsiella-pneumoniae
#15
Sarath Nath, Farzad Moussavi, Daniel Abraham, David Landman, John Quale
Objectives: Options for treatment of infections due to KPC-producing Klebsiella pneumoniae are limited and combination therapy is often recommended. In this report, the in vitro and in vivo activity of potential therapeutic agents and combinations was assessed against four KPC-producing K. pneumoniae isolates. Methods: Using clinically relevant concentrations, time-kill experiments and the Galleria mellonella model of infection were used to examine the activity of polymyxin B, ceftazidime/avibactam, meropenem, rifampicin and amikacin alone and in combination...
November 23, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29176971/occurrence-of-extended-spectrum-%C3%AE-lactamases-kpc-type-and-mcr-1-2-producing-enterobacteriaceae-from-wells-river-water-and-wastewater-treatment-plants-in-oltrep%C3%A3-pavese-area-northern-italy
#16
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
https://www.readbyqxmd.com/read/29160518/evaluation-of-carbapenem-resistant-enterobacteriaceae-in-a-tertiary-level-reference-hospital-in-rio-grande-do-sul-brazil
#17
Vinícius Victor Lorenzoni, Danielly da Costa Silva, Roberta Filipini Rampelotto, Patrícia Chaves Brites, Bárbara Villa, Rosmari Hörner
INTRODUCTION: The rapid global spread of carbapenem-resistant Enterobacteriaceae (CRE) is a threat to the health system. METHODS: We evaluated the antimicrobial susceptibility profiles of 70 CRE isolated in a tertiary hospital in Brazil between August and December 2015, and determined their resistance mechanisms. RESULTS: The most prevalent microorganism was Klebsiella pneumoniae (95.7%); it showed high-level resistance to carbapenems (>98%), with sensitivity to colistin (91...
September 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29126110/risks-of-infection-and-mortality-among-patients-colonized-with-kpc-producing-klebsiella-pneumoniae-validation-of-scores-and-proposal-for-management
#18
Angela Cano, Belén Gutiérrez-Gutiérrez, Isabel Machuca, Irene Gracia-Ahufinger, Elena Pérez-Nadales, Manuel Causse, Juan José Castón, Julia Guzman-Puche, Julian Torre-Giménez, Lara Kindelán, Luis Martínez-Martinez, Jesús Rodriguez-Baño, Julian Torre-Cisneros
Background: The management and indication of empirical treatment in Klebsiella pneumoniae-carbapenemase producing K. pneumoniae (KPC-Kp) colonized patients should be improved. Methods: A prospective cohort of 94 patients colonized by KPC-Kp was followed for 90 days to validate: (i) the Giannella risk score (GRS) to predict the development of any type of KPC-Kp infection and (ii) the INCREMENT-CPE score (ICS) to predict 30-day mortality in patients with infection...
November 8, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29109160/activity-of-meropenem-vaborbactam-in-mouse-models-of-infection-due-to-kpc-producing-carbapenem-resistant-enterobacteriaceae-cre
#19
Mojgan Sabet, Ziad Tarazi, Thomas Nolan, Jonathan Parkinson, Debora Rubio-Aparicio, Olga Lomovskaya, Michael N Dudley, David C Griffith
Meropenem-vaborbactam (Vabomere™) is highly active against Gram-negative pathogens, especially KPC-producing, carbapenem-resistant Enterobacteriaceae The objective of these studies was to evaluate the efficacy of meropenem alone and in combination with vaborbactam in mouse thigh and lung infection models. Thighs or lungs of neutropenic mice were infected with KPC-producing carbapenem-resistant Enterobacteriaceae with meropenem MICs ranging from ≤ 0.06 - 8 mg/L in the presence of vaborbactam 8 mg/L. Mice were treated with meropenem alone or meropenem in combination with vaborbactam every 2 hours for 24 hours to provide exposures comparable to 2 g doses of each component in humans...
November 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29091224/in-vitro-activity-of-plazomicin-against-%C3%AE-lactamase-producing-carbapenem-resistant-enterobacteriaceae-cre
#20
Yunliang Zhang, Ankita Kashikar, Karen Bush
Background: Carbapenem-resistant Enterobacteriaceae (CRE) represent an urgent threat because few drugs are available to treat infections caused by these pathogens. Plazomicin is a novel aminoglycoside that recently completed a Phase 3 clinical trial for treatment of infections caused by CRE. Methods: A set of 110 characterized unique CRE patient isolates from central Indiana healthcare centres was tested by microbroth dilution for susceptibility to plazomicin, and to reference aminoglycosides and carbapenems...
October 1, 2017: Journal of Antimicrobial Chemotherapy
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