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KPC multidrug resistance gram negative

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https://www.readbyqxmd.com/read/29627985/strategic-approaches-to-overcome-resistance-against-gram-negative-pathogens-using-%C3%AE-lactamase-inhibitors-and-%C3%AE-lactam-enhancers-the-activity-of-three-novel-diazabicyclooctanes-wck-5153-zidebactam-wck-5107-and-wck-4234
#1
Krisztina M Papp-Wallace, Nhu Q Nguyen, Michael R Jacobs, Christopher R Bethel, Melissa D Barnes, Vijay Kumar, Saralee Bajaksouzian, Susan D Rudin, Philip N Rather, Satish Bhavsar, Tadiparthi Ravikumar, Prasad K Deshpande, Vijay Patil, Ravindra Yeole, Sachin S Bhagwat, Mahesh V Patel, Focco van den Akker, Robert A Bonomo
Limited treatment options exist to combat infections caused by multidrug-resistant (MDR) Gram negative bacteria possessing broad-spectrum β-lactamases. The design of novel β-lactamase inhibitors is of paramount importance. Here, three novel diazabicyclooctanes (DBOs), WCK 5153, zidebactam (WCK 5107), and WCK 4234 (compounds 1-3) were synthesized and biochemically characterized against clinically important bacteria. Compound 3 inhibited class A, C and D β-lactamases with unprecedented k2/K values against OXA carbapenemases...
April 7, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29555630/comparison-of-septic-shock-due-to-mdr-acinetobacter-baumannii-or-klebsiella-pneumoniae-carbapenemase-producing-k-pneumoniae-in-icu-patients
#2
Alessandro Russo, Simone Giuliano, Giancarlo Ceccarelli, Francesco Alessandri, Alessandra Giordano, Grazia Brunetti, Mario Venditti
Objectives: a significant cause of mortality in intensive care unit (ICU) is represented by multidrug-resistant (MDR) gram-negative bacteria, such as MDR Acinetobacter baumannii (MDR-AB) and Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp). Aim of the present study was the comparison of clinical features, therapy and outcome of patients who developed septic shock due to either MDR-AB or KPC-Kp. Methods: were retrospectively analyzed patients admitted to the intensive care unit (ICU) of a teaching hospital, from November 2010 to December 2015, who developed septic shock due to MDR-AB or KPC-Kp infection...
March 19, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29484175/superbugs-in-the-supermarket-assessing-the-rate-of-contamination-with-third-generation-cephalosporin-resistant-gram-negative-bacteria-in-fresh-australian-pork-and-chicken
#3
Jade E McLellan, Joshua I Pitcher, Susan A Ballard, Elizabeth A Grabsch, Jan M Bell, Mary Barton, M Lindsay Grayson
Background: Antibiotic misuse in food-producing animals is potentially associated with human acquisition of multidrug-resistant (MDR; resistance to ≥ 3 drug classes) bacteria via the food chain. We aimed to determine if MDR Gram-negative (GNB) organisms are present in fresh Australian chicken and pork products. Methods: We sampled raw, chicken drumsticks (CD) and pork ribs (PR) from 30 local supermarkets/butchers across Melbourne on two occasions. Specimens were sub-cultured onto selective media for third-generation cephalosporin-resistant (3GCR) GNBs, with species identification and antibiotic susceptibility determined for all unique colonies...
2018: Antimicrobial Resistance and Infection Control
https://www.readbyqxmd.com/read/29427523/meropenem-and-vaborbactam-stepping-up-the-battle-against-carbapenem-resistant-enterobacteriaceae
#4
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/29340452/detection-of-multidrug-resistant-pseudomonas-aeruginosa-harboring-bla-ges-1-and-bla-ges-11-in-recife-brazil
#5
Valdemir Vicente da Silva Júnior, Laura Durão Ferreira, Lílian Rodrigues Alves, Adriane Borges Cabral, Paula Regina Luna de Araújo Jácome, Paulo Sérgio Ramos de Araújo, Ana Catarina de Souza Lopes, Maria Amélia Vieira Maciel
INTRODUCTION: Pseudomonas aeruginosa, an important pathogen globally, presents several resistance mechanisms. This study aimed to investigate the presence of bla GES in clinical isolates of Pseudomonas aeruginosa obtained from various clinical specimens from patients admitted to three different hospitals in Recife, Brazil. The Guiana extended spectrum beta-lactamase (GES) enzymes are responsible for conferring broad spectrum resistance to beta-lactam drugs, including the carbapenems. METHODS: A total of 100 carbapenem-resistant P...
November 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29232103/game-changers-new-%C3%AE-lactamase-inhibitor-combinations-targeting-antibiotic-resistance-in-gram-negative-bacteria
#6
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...
February 9, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28827415/antimicrobial-activity-of-ceftazidime-avibactam-tested-against-multidrug-resistant-enterobacteriaceae-and-pseudomonas-aeruginosa-isolates-from-u-s-medical-centers-2013-to-2016
#7
Helio S Sader, Mariana Castanheira, Dee Shortridge, Rodrigo E Mendes, Robert K Flamm
The in vitro activity of ceftazidime-avibactam and many comparator agents was determined against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 Pseudomonas aeruginosa isolates. The isolates were consecutively collected from 94 U.S. hospitals, and all isolates were tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). Enterobacteriaceae isolates resistant to carbapenems (CRE) and/or ceftazidime-avibactam (MIC ≥ 16 μg/ml) were evaluated for the presence of genes encoding extended-spectrum β-lactamases and carbapenemases...
November 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28807400/incx3-plasmid-harboring-a-non-tn4401-genetic-element-ntekpc-in-a-hospital-associated-clone-of-kpc-2-producing-klebsiella-pneumoniae-st340-cg258
#8
Louise T Cerdeira, Marcos P V Cunha, Gabriela R Francisco, Maria Fernanda C Bueno, Bruna F Araujo, Rosineide M Ribas, Paulo P Gontijo-Filho, Terezinha Knöbl, Doroti de Oliveira Garcia, Nilton Lincopan
IncX-type plasmids have achieved clinical significance for their contribution in the dissemination of genes confering resistance to carbapenems (most blaKPC- and blaNDM-type genes) and polymyxins (mcr-type genes), both antibiotics considered last resort for multidrug-resistant Gram-negative infections. In this study, we report the identification and complete sequence analysis of an IncX3 plasmid (designated pKP1194a) carrying a non-Tn4401 genetic element (NTEKPC) of tnpR-tnpA (partial)-blaKPC-2-ΔISKpn6/traN, originating from a hospital-associated lineage of K...
July 1, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28758635/cluster-distinguishing-genotypic-and-phenotypic-diversity-of-carbapenem-resistant-gram-negative-bacteria-in-solid-organ-transplantation-patients-a-comparative-study
#9
Theodoros Karampatakis, Anastasia Geladari, Lida Politi, Charalampos Antachopoulos, Elias Iosifidis, Olga Tsiatsiou, Aggeliki Karyoti, Vasileios Papanikolaou, Athanassios Tsakris, Emmanuel Roilides
PURPOSE: Solid-organ transplant recipients may display high rates of colonization and/or infection by multidrug-resistant bacteria. We analysed and compared the phenotypic and genotypic diversity of carbapenem-resistant (CR) strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolated from patients in the Solid Organ Transplantation department of our hospital. METHODOLOGY: Between March 2012 and August 2013, 56 CR strains from various biological fluids underwent antimicrobial susceptibility testing with VITEK 2, molecular analysis by PCR amplification and genotypic analysis with pulsed-field gel electrophoresis (PFGE)...
July 31, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28652234/meropenem-vaborbactam-tested-against-contemporary-gram-negative-isolates-collected-worldwide-during-2014-including-carbapenem-resistant-kpc-producing-multidrug-resistant-and-extensively-drug-resistant-enterobacteriaceae
#10
Mariana Castanheira, Michael D Huband, Rodrigo E Mendes, Robert K Flamm
We evaluated the activity of meropenem-vaborbactam against contemporary nonfastidious Gram-negative clinical isolates, including Enterobacteriaceae isolates with resistance phenotypes and carbapenemase genotypes. Meropenem-vaborbactam (inhibitor at 8 μg/ml) and comparators were susceptibility tested by reference broth microdilution methods against 14,304 Gram-negative clinical isolates collected worldwide during 2014. Carbapenemase-encoding genes were screened by PCR and sequencing. Meropenem-vaborbactam (MIC50/90, ≤0...
September 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28650688/multidrug-resistant-enterobacteriaceae-in-lebanese-hospital-wastewater-implication-in-the-one-health-concept
#11
Ziad Daoud, Jina Farah, Elie Salem Sokhn, Khalil El Kfoury, Elias Dahdouh, Khalil Masri, Claude Afif, Roula M Abdel-Massih, Ghassan M Matar
Extended-spectrum beta-lactamases (ESBL) and carbapenemase-producing organisms pose severe problems for hospitalized patients. In the absence of efficient sanitation and sewage disposal, the risks for transmission of hospital organisms into the community are high. Our objectives were to study the occurrence and mechanisms of resistance of multidrug-resistant gram-negative bacilli in two Lebanese hospital sewage treatment plants. Wastewater samples were collected, filtered, and cultivated on MacConckey+cefotaxime agars...
June 26, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28485708/molecular-study-of-carbapenemase-genes-in-clinical-isolates-of-enterobacteriaceae-resistant-to-carbapenems-and-determining-their-clonal-relationship-using-pulsed-field-gel-electrophoresis
#12
Fereshteh Shahcheraghi, Mohammad Mehdi Aslani, Hassan Mahmoudi, Zahra Karimitabar, Hamid Solgi, Abbas Bahador, Mohammad Yousef Alikhani
PURPOSE: Enterobacteriaceae is a large family of Gram-negative bacteria that are considered as normal gut flora. They are the most common human pathogens. The main objective of this study was to investigate the carbapenemase genes in clinical isolates of Enterobacteriaceae resistant to carbapenem antibiotics and determine their clonal relationship using pulsed-field gel electrophoresis (PFGE). METHODOLOGY: In the present study, bacteria were isolated and identified via conventional biochemical tests and API 20NE...
May 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28444620/environmental-pollution-with-antimicrobial-agents-from-bulk-drug-manufacturing-industries-in-hyderabad-south-india-is-associated-with-dissemination-of-extended-spectrum-beta-lactamase-and-carbapenemase-producing-pathogens
#13
Christoph Lübbert, Christian Baars, Anil Dayakar, Norman Lippmann, Arne C Rodloff, Martina Kinzig, Fritz Sörgel
PURPOSE: High antibiotic and antifungal concentrations in wastewater from anti-infective drug production may exert selection pressure for multidrug-resistant (MDR) pathogens. We investigated the environmental presence of active pharmaceutical ingredients and their association with MDR Gram-negative bacteria in Hyderabad, South India, a major production area for the global bulk drug market. METHODS: From Nov 19 to 28, 2016, water samples were collected from the direct environment of bulk drug manufacturing facilities, the vicinity of two sewage treatment plants, the Musi River, and habitats in Hyderabad and nearby villages...
August 2017: Infection
https://www.readbyqxmd.com/read/28442305/transfer-of-kpc-2-carbapenemase-from-klebsiella-pneumoniae-to-enterobacter-cloacae-in-a-patient-receiving-meropenem-therapy
#14
Evelin Rodrigues Martins, Cássia Fernanda Estofolete, Andressa Batista Zequini, Louise Cerdeira, Doroti de Oliveira Garcia, Maria Fernanda Campagnari Bueno, Gabriela Rodrigues Francisco, Leonardo Neves de Andrade, Ana Lúcia da Costa Darini, Fernanda Modesto Tolentino, Tiago Casella, Nilton Lincopan, Mara Corrêa Lelles Nogueira
The horizontal transfer of a plasmid bearing the blaKPC-2 gene from K. pneumoniae to E. cloacae infecting the respiratory tract of a patient during meropenem therapy was elucidated. This finding is particularly worrisome, since these drugs are of last resort for multidrug-resistant Gram-negative pathogens.
April 12, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28069649/antimicrobial-activity-of-ceftazidime-avibactam-against-gram-negative-bacteria-isolated-from-patients-hospitalized-with-pneumonia-in-u-s-medical-centers-2011-to-2015
#15
Helio S Sader, Mariana Castanheira, Robert K Flamm
Bacterial isolates were collected from patients hospitalized with pneumonia (PHP), including ventilator-associated pneumonia (VAP), from 76 U.S. medical centers in 2011 to 2015. The Gram-negative organisms (n = 11,185, including 1,097 from VAP) were tested for susceptibility to ceftazidime-avibactam and comparators by the broth microdilution method. β-Lactamase-encoding genes were screened using a microarray-based assay on selected isolates. Pseudomonas aeruginosa and Klebsiella spp. were the most common Gram-negative bacteria isolated from PHP and VAP...
April 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27942042/faecal-carriage-of-gram-negative-multidrug-resistant-bacteria-among-patients-hospitalized-in-two-centres-in-ulaanbaatar-mongolia
#16
Bayaraa Baljin, Ganbaatar Baldan, Battogtokh Chimeddorj, Khosbayar Tulgaa, Batbaatar Gunchin, Tsogtsaikhan Sandag, Klaus Pfeffer, Colin R MacKenzie, Andreas F Wendel
Gram-negative multidrug-resistant organisms (GN-MDRO) producing β-lactamases (ESBL, plasmid-mediated AmpC β-lactamases and carbapenemases) are increasingly reported throughout Asia. The aim of this surveillance study was to determine the rate of bacterial colonization in patients from two hospitals in the Mongolian capital Ulaanbaatar. Rectal swabs were obtained from patients referred to the National Traumatology and Orthopaedics Research Centre (NTORC) or the Burn Treatment Centre (BTC) between July and September 2014, on admission and again after 14 days...
2016: PloS One
https://www.readbyqxmd.com/read/27934829/does-the-presence-of-klebsiella-pneumoniae-carbapenemase-and-new-delhi-metallo-%C3%AE-lactamase-1-genes-in-pathogens-lead-to-fatal-outcome
#17
P Mathur, S Sagar, S Kumar, V Sharma, D Gupta, S Lalwani, R Rani, A Muruganantham
INTRODUCTION: Infections due to multidrug-resistant (MDR) pathogens are a medical challenge. There is considerable apprehension among clinicians regarding pathogens reported as carrying New Delhi metallo-β-lactamase-1 (NDM) and Klebsiella pneumoniae carbapenemase (KPC) genes from their patients. In the face of extremely high rates of antimicrobial resistance, it is essential to gauge the clinical significance of isolation of pathogens carrying these genes from clinical samples. This study compares the outcome of patients infected with pathogens carrying NDM/KPC genes versus those without these genes...
October 2016: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27818808/persistent-bacteremia-from-pseudomonas-aeruginosa-with-in-vitro-resistance-to-the-novel-antibiotics-ceftolozane-tazobactam-and-ceftazidime-avibactam
#18
Louie Mar Gangcuangco, Patricia Clark, Cynthia Stewart, Goran Miljkovic, Zane K Saul
Ceftazidime-avibactam and ceftolozane-tazobactam are new antimicrobials with activity against multidrug-resistant Pseudomonas aeruginosa. We present the first case of persistent P. aeruginosa bacteremia with in vitro resistance to these novel antimicrobials. A 68-year-old man with newly diagnosed follicular lymphoma was admitted to the medical intensive care unit for sepsis and right lower extremity cellulitis. The patient was placed empirically on vancomycin and piperacillin-tazobactam. Blood cultures from Day 1 of hospitalization grew P...
2016: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/27716983/pharmacokinetics-of-ceftazidime-avibactam-in-two-patients-with-kpc-producing-klebsiella-pneumoniae-bacteremia-and-renal-impairment
#19
John J Veillette, James Truong, Steven C Forland
Limited data exist regarding optimal dosing of ceftazidime/avibactam (C/A) in patients with unique physiology, who were excluded from published clinical trials. Data are also lacking regarding clinical efficacy of C/A in patients with infections due to multidrug-resistant gram-negative pathogens. To expand knowledge in these areas, we present pharmacokinetic data from two patients with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infections, both of whom had renal impairment, and one of whom was morbidly obese...
November 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27585707/molecular-epidemiology-of-carbapenem-resistant-gram-negative-bacilli-from-infected-pediatric-population-in-tertiary-care-hospitals-in-medell%C3%A3-n-colombia-an-increasing-problem
#20
Johanna M Vanegas, O Lorena Parra, J Natalia Jiménez
BACKGROUND: Gram-negative bacilli are a cause of serious infections in the pediatric population. Carbapenem are the treatment of choice for infections caused by multidrug-resistant Gram-negative bacilli, but the emergence of carbapenem resistance has substantially reduced access to effective antimicrobial regimens. Children are a population vulnerable to bacterial infections and the emergence of resistance can worsen prognosis. The aim of this study is to describe the clinical and molecular characteristics of infections caused by carbapenem-resistant Gram-negative bacilli in pediatric patients from five tertiary-care hospitals in Medellín, Colombia...
September 1, 2016: BMC Infectious Diseases
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