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https://www.readbyqxmd.com/read/29232103/game-changers-new-%C3%AE-lactamase-inhibitor-combinations-targeting-antibiotic-resistance-in-gram-negative-bacteria
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/29038270/activity-of-meropenem-vaborbactam-against-carbapenem-resistant-enterobacteriaceae-in-a-murine-model-of-pyelonephritis
#11
William J Weiss, Mark E Pulse, Phung Nguyen, Kelly Peterson, Jessica Silva, Jerry W Simecka, David Valtierra, Mojgan Sabet, David C Griffith
The recently approved combination of meropenem-vaborbactam (Vabomere™) is highly active against Gram-negative pathogens, especially KPC-producing, carbapenem-resistant Enterobacteriaceae We evaluated the efficacy of meropenem-vaborbactam against three clinically relevant isolates in a murine polynephritis model. Data indicated that the combination of meropenem-vaborbactam significantly increased the bacterial killing compared to the untreated controls. These data suggest that this combination may have utility in the treatment of complicated urinary tract infections due to KPC-producing, carbapenem-resistant Enterobacteriaceae...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29020404/colistin-vs-ceftazidime-avibactam-in-the-treatment-of-infections-due-to-carbapenem-resistant-enterobacteriaceae
#12
David van Duin, Judith J Lok, Michelle Earley, Eric Cober, Sandra S Richter, Federico Perez, Robert A Salata, Robert C Kalayjian, Richard R Watkins, Yohei Doi, Keith S Kaye, Vance G Fowler, David L Paterson, Robert A Bonomo, Scott Evans
Background: The efficacy of ceftazidime-avibactam - a cephalosporin-β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Enterobacteriaceae (CRE) - as compared to colistin remains unknown. Methods: Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on resistance against carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study...
September 4, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28951106/in-vitro-interaction-of-ceftazidime-avibactam-in-combination-with-different-antimicrobials-against-kpc-producing-klebsiella-pneumoniae-clinical-isolates
#13
Paolo Gaibani, Russell E Lewis, Silvia L Volpe, Maddalena Giannella, Caterina Campoli, Maria Paola Landini, PierLuigi Viale, Maria Carla Re, Simone Ambretti
OBJECTIVES: Combination therapy has been recommended when using ceftazidime-avibactam (CAZ-AVI) for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal combination is unknown. Six common antimicrobial agents (ertapenem, imipenem, meropenem, gentamicin, tigecycline, and ciprofloxacin) were evaluated for synergy with the recently approved cephalosporin-β-lactamase inhibitor combination CAZ-AVI in this study. METHODS: Different antimicrobial combinations were tested against 13 KPC-Kp, including CAZ-AVI-susceptible (n=11) and resistant (n=2) clinical isolates...
September 22, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28916900/were-all-carbapenemases-created-equal-treatment-of-ndm-producing-extensively-drug-resistant-enterobacteriaceae-a-case-report-and-literature-review
#14
REVIEW
Vindana Chibabhai, Trusha Nana, Norma Bosman, Teena Thomas, Warren Lowman
PURPOSE: There is currently a paucity of published literature focused on the treatment of infections caused by NDM-producing organisms. METHODS: We describe a case of a bacteraemia caused by an extensively drug-resistant (XDR) New Delhi metallo-β-lactamase (NDM)-producing Serratia marcescens and review the treatment options for XDR NDM-producing Enterobacteriaceae. RESULTS: Infections caused by New Delhi beta-lactamase (NDM)-producing Enterobacteriaceae are becoming increasingly prevalent worldwide...
September 15, 2017: Infection
https://www.readbyqxmd.com/read/28893690/new-agents-for-the-treatment-of-infections-with-gram-negative-bacteria-restoring-the-miracle-or-false-dawn
#15
REVIEW
H Wright, R A Bonomo, D L Paterson
BACKGROUND: Antibiotic resistance in Gram-negative resistance has developed without a commensurate response in the successful development of antibiotic agents, though recent progress has been made. AIMS: This review aims to provide a summary of the existing evidence on efficacy, spectrum of activity and the development of resistance of new agents that have been licensed or have completed advanced clinical trials and that possess activity against resistant Gram-negative organisms...
October 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28893689/management-of-kpc-producing-klebsiella-pneumoniae-infections
#16
REVIEW
M Bassetti, D R Giacobbe, H Giamarellou, C Viscoli, G L Daikos, G Dimopoulos, F G De Rosa, E J Giamarellos-Bourboulis, G M Rossolini, E Righi, I Karaiskos, M Tumbarello, D P Nicolau, P L Viale, G Poulakou
BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas. AIMS: To provide practical suggestion for physicians dealing with the management of KPC-KP infections in critically ill patients, based on expert opinions. SOURCES: PubMed search for relevant publications related to the management of KPC-KP infections. CONTENTS: A panel of experts developed a list of 12 questions to be addressed...
September 9, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28886559/sewage-treatment-effluents-in-delhi-a-key-contributor-of-%C3%AE-lactam-resistant-bacteria-and-genes-to-the-environment
#17
Manisha Lamba, Shaikh Ziauddin Ahammad
Rapid emergence of antibiotic resistance (AR) in developing countries is posing a greater health risk and increasing the global disease burden. Lack of access to safe drinking water, poor sanitation and inadequate sewage treatment facilities in these countries are fueling the problem associated with emergence of AR. Rapid proliferation of AR mediated by treated and untreated discharges from sewage treatment plants (STPs) is a prime public health concern. This study aims to understand the occurrence, fate, and routes of proliferation of carbapenem (KPC) and extended spectrum β-lactam (ESBL) resistant bacteria, and selected resistant genes in the samples collected from different unit operations in 12 STPs in New Delhi over two seasons...
August 28, 2017: Chemosphere
https://www.readbyqxmd.com/read/28841710/inhibition-of-rock1-kinase-modulates-both-tumor-cells-and-stromal-fibroblasts-in-pancreatic-cancer
#18
Clifford J Whatcott, Serina Ng, Michael T Barrett, Galen Hostetter, Daniel D Von Hoff, Haiyong Han
ROCK, or Rho-associated coiled coil-containing protein kinase, is a member of the AGC kinase family and has been shown to play a role in cell migration, ECM synthesis, stress-fiber assembly, and cell contraction. Increased ROCK expression has been reported in multiple pathological conditions, including cancer. Here, we report increased expression of ROCK 1 in pancreatic tumor epithelial cells as well as in cancer associated fibroblasts (CAF). In our analysis, 62% of tumor samples exhibited ≥2+ in staining intensity by IHC analysis, versus 40% of adjacent normal tissue samples (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/28840351/activity-of-temocillin-and-15-other-agents-including-fosfomycin-and-colistin-against-enterobacteriaceae-in-hong-kong
#19
Margaret Ip, Christopher K Lai, Kitty S C Fung, K-Tak Wong, Chendi Zhu, Sebastien Van de Velde, Dominic N Tsang, Peter Hawkey
Limited data are available on temocillin susceptibilities in Enterobacteriaceae from Asian countries where antimicrobial resistance is prevalent. The in vitro activities of temocillin and 15 commonly used antimicrobials against 613 non-duplicate blood (n = 310) and urine (with clinically significant bacteriuria; n = 303) isolates of Enterobacteriaceae from patients who attended 3 out of 7 clusters of public hospitals of the Hospital Authority, Hong Kong, during 2015/2016 were tested. Minimum inhibitory concentrations (MICs) were determined by Clinical and Laboratory Standards Institute (CLSI) microbroth dilution (agar dilution with fosfomycin)...
August 25, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28837596/membrane-active-macromolecules-kill-antibiotic-tolerant-bacteria-and-potentiate-antibiotics-towards-gram-negative-bacteria
#20
Divakara S S M Uppu, Mohini M Konai, Paramita Sarkar, Sandip Samaddar, Isabel C M Fensterseifer, Celio Farias-Junior, Paramanandam Krishnamoorthy, Bibek R Shome, Octávio L Franco, Jayanta Haldar
Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria...
2017: PloS One
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