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Bonomo Robert

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https://www.readbyqxmd.com/read/28912448/a-general-reaction-mechanism-for-carbapenem-hydrolysis-by-mononuclear-and-binuclear-metallo-%C3%AE-lactamases
#1
María-Natalia Lisa, Antonela R Palacios, Mahesh Aitha, Mariano M González, Diego M Moreno, Michael W Crowder, Robert A Bonomo, James Spencer, David L Tierney, Leticia I Llarrull, Alejandro J Vila
Carbapenem-resistant Enterobacteriaceae threaten human health, since carbapenems are last resort drugs for infections by such organisms. Metallo-β-lactamases (MβLs) are the main mechanism of resistance against carbapenems. Clinically approved inhibitors of MBLs are currently unavailable as design has been limited by the incomplete knowledge of their mechanism. Here, we report a biochemical and biophysical study of carbapenem hydrolysis by the B1 enzymes NDM-1 and BcII in the bi-Zn(II) form, the mono-Zn(II) B2 Sfh-I and the mono-Zn(II) B3 GOB-18...
September 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28893775/a-nosocomial-outbreak-of-extensively-drug-resistant-xdr-acinetobacter-baumannii-isolates-containing-blaoxa-237-encoded-on-a-plasmid
#2
Andrea M Hujer, Paul G Higgins, Susan D Rudin, Genevieve L Buser, Steven H Marshall, Kyriaki Xanthopoulou, Harald Seifert, Laura J Rojas, T Nicholas Domitrovic, P Maureen Cassidy, Margaret C Cunningham, Robert Vega, Jon P Furuno, Christopher D Pfeiffer, Zintars G Beldavs, Meredith S Wright, Michael R Jacobs, Mark D Adams, Robert A Bonomo
Carbapenem antibiotics are among the mainstay for treating infections caused by Acinetobacter baumannii, especially in the Northwest United States where carbapenem resistant A. baumannii remain relatively rare. However, between June 2012 and October 2014, an outbreak of carbapenem-resistant A. baumannii occurred in 16 patients from 5 healthcare facilities in the state of Oregon. All isolates were defined as extensively-drug resistant (XDR). MLST revealed that the isolates belonged to sequence type 2 (international clone 2, IC2), and were greater than 95% similar by rep-PCR analysis...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28893690/new-agents-for-the-treatment-of-infections-with-gram-negative-bacteria-restoring-the-miracle-or-false-dawn
#3
REVIEW
Hugh Wright, Robert A Bonomo, David 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 completed advanced clinical trials that possess activity against resistant gram-negative organisms...
September 8, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28870269/failure-to-communicate-transmission-of-extensively-drug-resistant-bla-oxa-237-containing-acinetobacter-baumannii-multiple-facilities-in-oregon-2012-2014
#4
Genevieve L Buser, P Maureen Cassidy, Margaret C Cunningham, Susan Rudin, Andrea M Hujer, Robert Vega, Jon P Furuno, Steven H Marshall, Paul G Higgins, Michael R Jacobs, Meredith S Wright, Mark D Adams, Robert A Bonomo, Christopher D Pfeiffer, Zintars G Beldavs
OBJECTIVE To determine the scope, source, and mode of transmission of a multifacility outbreak of extensively drug-resistant (XDR) Acinetobacter baumannii. DESIGN Outbreak investigation. SETTING AND PARTICIPANTS Residents and patients in skilled nursing facilities, long-term acute-care hospital, and acute-care hospitals. METHODS A case was defined as the incident isolate from clinical or surveillance cultures of XDR Acinetobacter baumannii resistant to imipenem or meropenem and nonsusceptible to all but 1 or 2 antibiotic classes in a patient in an Oregon healthcare facility during January 2012-December 2014...
September 5, 2017: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/28830942/diabetes-exacerbates-infection-via-hyperinflammation-by-signaling-through-tlr4-and-rage
#5
Travis B Nielsen, Paul Pantapalangkoor, Jun Yan, Brian M Luna, Ken Dekitani, Kevin Bruhn, Brandon Tan, Justin Junus, Robert A Bonomo, Ann Marie Schmidt, Michael Everson, Frederick Duncanson, Terence M Doherty, Lin Lin, Brad Spellberg
For more than a century, diabetic patients have been considered immunosuppressed due to defects in phagocytosis and microbial killing. We confirmed that diabetic mice were hypersusceptible to bacteremia caused by Gram-negative bacteria (GNB), dying at inocula nonlethal to nondiabetic mice. Contrary to the pervasive paradigm that diabetes impedes phagocytic function, the bacterial burden was no greater in diabetic mice despite excess mortality. However, diabetic mice did exhibit dramatically increased levels of proinflammatory cytokines in response to GNB infections, and immunosuppressing these cytokines with dexamethasone restored their resistance to infection, both of which are consistent with excess inflammation...
August 22, 2017: MBio
https://www.readbyqxmd.com/read/28809565/dipicolinic-acid-derivatives-as-inhibitors-of-new-delhi-metallo-%C3%AE-lactamase-1
#6
Allie Y Chen, Pei W Thomas, Alesha C Stewart, Alexander Bergstrom, Zishuo Cheng, Callie Miller, Christopher R Bethel, Steven H Marshall, Cy V Credille, Christopher L Riley, Richard C Page, Robert A Bonomo, Michael W Crowder, David L Tierney, Walter Fast, Seth M Cohen
The efficacy of β-lactam antibiotics is threatened by the emergence and global spread of metallo-β-lactamase (MBL) mediated resistance, specifically New Delhi metallo-β-lactamase-1 (NDM-1). By utilization of fragment-based drug discovery (FBDD), a new class of inhibitors for NDM-1 and two related β-lactamases, IMP-1 and VIM-2, was identified. On the basis of 2,6-dipicolinic acid (DPA), several libraries were synthesized for structure-activity relationship (SAR) analysis. Inhibitor 36 (IC50 = 80 nM) was identified to be highly selective for MBLs when compared to other Zn(II) metalloenzymes...
September 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28807908/activity-of-the-%C3%AE-lactamase-inhibitor-ln-1-255-against-carbapenem-hydrolyzing-class-d-%C3%AE-lactamases-from-acinetobacter-baumannii
#7
Juan Carlos Vázquez-Ucha, María Maneiro, Marta Martínez-Guitián, John Buynak, Christopher R Bethel, Robert A Bonomo, Germán Bou, Margarita Poza, Concepción González-Bello, Alejandro Beceiro
The number of infections caused by Gram-negative pathogens carrying carbapenemases is increasing, and the group of carbapenem-hydrolyzing class D β-lactamases (CHDLs) is especially problematic. Several clinically important CHDLs have been identified in A. baumannii, including OXA-23, OXA-24/40, OXA-58, OXA-143, OXA-235, and the chromosomally encoded OXA-51. The selection and dissemination of carbapenem-resistant A. baumannii strains constitutes a serious global threat. Carbapenems have been successfully utilized as last resort antibiotics for the treatment of multi-drug-resistant A...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28782704/geographical-variation-in-therapy-for-bloodstream-infections-due-to-multidrug-resistant-enterobacteriaceae-a-post-hoc-analysis-of-the-increment-study
#8
Patrick N A Harris, M Diletta Pezzani, Belén Gutiérrez-Gutiérrez, Pierluigi Viale, Po-Ren Hsueh, Patricia Ruiz-Garbajosa, Mario Venditti, Mario Tumbarello, Carolina Navarro-Francisco, Esther Calbo, Murat Akova, Helen Giamarellou, Antonio Oliver, Benito Almirante, Oriol Gasch, Luis Martínez-Martínez, Mitchell J Schwaber, George Daikos, Johann Pitout, Carmen Peña, Alicia Hernández-Torres, Yohei Doi, Federico Pérez, Felipe Francisco Tuon, Evelina Tacconelli, Yehuda Carmeli, Robert A Bonomo, Álvaro Pascual, David L Paterson, Jesús Rodríguez-Baño
We aimed to describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). 1,482 patients in 12 countries were included from an observational study of BSI caused by ESBL-E or CPE. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of β-lactam/β-lactamase inhibitors (BLBLI) or carbapenems, targeted use of BLBLI for ESBL-E and use of targeted combination therapy for CPE...
August 3, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28625698/a-cold-hard-menace-a-contaminated-ice-machine-as-a-potential-source-for-transmission-of-carbapenem-resistant-acinetobacter-baumannii
#9
Anubhav Kanwar, T Nicholas Domitrovic, Sreelatha Koganti, Peter Fuldauer, Jennifer L Cadnum, Robert A Bonomo, Curtis J Donskey
During an investigation of potential sources of transmission of multidrug-resistant gram-negative bacilli on a spinal cord injury unit, we recovered genetically related carbapenem-resistant Acinetobacter baumannii isolates from the stool of 3 patients, the hands of a nurse, and an ice machine water outlet spout and drain. Our findings suggest that contaminated ice machines could serve as a potential reservoir for dissemination of multidrug-resistant gram-negative bacilli.
June 15, 2017: American Journal of Infection Control
https://www.readbyqxmd.com/read/28536161/correction-for-evans-et-al-informing-antibiotic-treatment-decisions-evaluating-rapid-molecular-diagnostics-to-identify-susceptibility-and-resistance-to-carbapenems-against-acinetobacter-spp-in-primers-iii
#10
Scott R Evans, Andrea M Hujer, Hongyu Jiang, Carol B Hill, Kristine M Hujer, Jose R Mediavilla, Claudia Manca, Thuy Tien T Tran, T Nicholas Domitrovic, Paul G Higgins, Harald Seifert, Barry N Kreiswirth, Robin Patel, Michael R Jacobs, Liang Chen, Rangarajan Sampath, Thomas Hall, Christine Marzan, Vance G Fowler, Henry F Chambers, Robert A Bonomo
No abstract text is available yet for this article.
June 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28521000/the-ecology-of-extended-spectrum-%C3%AE-lactamases-esbls-in-the-developed-world
#11
Yohei Doi, Alina Iovleva, Robert A Bonomo
Background: Since the initial appearance in the 1980s, Enterobacteriaceae producing extended-spectrum β-lactamase (ESBL) have increased in prevalence and emerged as a major antimicrobial-resistant pathogen. The source of these antimicrobial-resistant bacteria in the developed world is an area of active investigation. Methods: A standard internet search was conducted with a focus on the epidemiology and potential sources of ESBL-producing Enterobacteriaceae in the developed world...
April 1, 2017: Journal of Travel Medicine
https://www.readbyqxmd.com/read/28482143/discovery-of-1-hydroxypyridine-2-1h-thione-6-carboxylic-acid-as-a-first-in-class-low-cytotoxic-nanomolar-metallo-%C3%AE-lactamase-inhibitor
#12
Woo Shik Shin, Alexander Bergstrom, Robert A Bonomo, Michael W Crowder, Ramaiah Muthyala, Yuk Yin Sham
VIM-2 is one of the most common carbapenem-hydrolyzing metallo β-lactamases (MBL) found in many drug-resistant Gram-negative bacterial strains. Currently, there is a lack of effective lead compounds with optimal therapeutic potential within our drug development pipeline. Here we report the discovery of 1-hydroxypyridine-2(1H)-thione-6-carboxylic acid (3) as a first-in-class metallo β-lactamase inhibitor (MBLi) with a potent inhibition Ki of 13 nm against VIM-2 that corresponds to a remarkable 0.99 ligand efficiency...
June 7, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28468855/simple-screening-for-carbapenemase-producing-enterobacteriaceae-by-moxalactam-susceptibility-testing
#13
LETTER
Waka Imai, Masakazu Sasaki, Kotaro Aoki, Yoshikazu Ishii, Robert A Bonomo, Tse Hsien Koh, Hinako Murakami, Toshisuke Morita, Kazuhiro Tateda
No abstract text is available yet for this article.
July 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28461314/ndm-5-and-oxa-181-beta-lactamases-a-significant-threat-continues-to-spread-in-the-americas
#14
Laura J Rojas, Andrea M Hujer, Susan D Rudin, Meredith S Wright, T Nicholas Domitrovic, Steven H Marshall, Kristine M Hujer, Sandra S Richter, Eric Cober, Federico Perez, Mark D Adams, David van Duin, Robert A Bonomo
Among Gram-negative bacteria, carbapenem-resistant infections pose a serious and life-threatening challenge. Here, the CRACKLE network reports a sentinel detection and characterization of a carbapenem-resistant Klebsiella pneumoniae ST147 isolate harboring blaNDM-5 and blaOXA-181 from a young man who underwent abdominal surgery in India. blaNDM-5 was located on an IncFII plasmid of ≈90 kb, whereas blaOXA-181 was chromosomally encoded. Resistome and genome analysis demonstrated multiple copies of the transposable element IS26 and a "hot-spot region" in the IncFII plasmid...
July 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28442293/effect-of-appropriate-combination-therapy-on-mortality-of-patients-with-bloodstream-infections-due-to-carbapenemase-producing-enterobacteriaceae-increment-a-retrospective-cohort-study
#15
Belén Gutiérrez-Gutiérrez, Elena Salamanca, Marina de Cueto, Po-Ren Hsueh, Pierluigi Viale, José Ramón Paño-Pardo, Mario Venditti, Mario Tumbarello, George Daikos, Rafael Cantón, Yohei Doi, Felipe Francisco Tuon, Ilias Karaiskos, Elena Pérez-Nadales, Mitchell J Schwaber, Özlem Kurt Azap, Maria Souli, Emmanuel Roilides, Spyros Pournaras, Murat Akova, Federico Pérez, Joaquín Bermejo, Antonio Oliver, Manel Almela, Warren Lowman, Benito Almirante, Robert A Bonomo, Yehuda Carmeli, David L Paterson, Alvaro Pascual, Jesús Rodríguez-Baño
BACKGROUND: The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. METHODS: In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries...
July 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28428984/a-comparison-of-molecular-typing-methods-applied-to-enterobacter-cloacae-complex-hsp60-sequencing-rep-pcr-and-mlst
#16
Roberto A Viau, Lee M Kiedrowski, Barry N Kreiswirth, Mark Adams, Federico Perez, Dror Marchaim, Dubert M Guerrero, Keith S Kaye, Latania K Logan, Maria Virginia Villegas, Robert A Bonomo
Molecular typing using repetitive sequenced-based PCR (rep-PCR) and hsp60 sequencing were applied to a collection of diverse Enterobacter cloacae complex isolates. To determine the most practical method for reference laboratories, we analyzed 71 E. cloacae complex isolates from sporadic and outbreak occurrences originating from 4 geographic areas. While rep-PCR was more discriminating, hsp60 sequencing provided a broader and a more objective geographical tracking method similar to multilocus sequence typing (MLST)...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28418318/carbapenem-resistant-enterobacter-cloacae-in-patients-from-the-us-veterans-health-administration-2006-2015
#17
Brigid M Wilson, Nadim G El Chakhtoura, Sachin Patel, Elie Saade, Curtis J Donskey, Robert A Bonomo, Federico Perez
We analyzed carbapenem-resistant Enterobacteriaceae (CRE) trends among patients from the US Veterans Health Administration (VHA). After the emergence of CRE in the eastern United States, resistance rates remained stable in Klebsiella pneumoniae but increased in Enterobacter cloacae complex, suggesting a "second epidemic". VHA offers a vantage point for monitoring nationwide CRE trends.
May 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28398924/factors-leading-to-transmission-risk-of-acinetobacter-baumannii
#18
MULTICENTER STUDY
Kerri A Thom, Clare Rock, Sarah S Jackson, J Kristie Johnson, Arjun Srinivasan, Laurence S Magder, Mary-Claire Roghmann, Robert A Bonomo, Anthony D Harris
OBJECTIVES: To identify patient and healthcare worker factors associated with transmission risk of Acinetobacter baumannii during patient care. DESIGN: Prospective cohort study. SETTING: ICUs at a tertiary care medical center. PATIENTS: Adult ICU patients known to be infected or colonized with A. baumannii. MEASUREMENTS AND MAIN RESULTS: Cultures of skin, respiratory tract, and the perianal area were obtained from participants and evaluated for the presence of A...
July 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28350903/advancing-diagnostics-to-address-antibacterial-resistance-the-diagnostics-and-devices-committee-of-the-antibacterial-resistance-leadership-group
#19
Ephraim L Tsalik, Elizabeth Petzold, Barry N Kreiswirth, Robert A Bonomo, Ritu Banerjee, Ebbing Lautenbach, Scott R Evans, Kimberly E Hanson, Jeffrey D Klausner, Robin Patel
Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and use true gold standards for development. In contrast, infectious diseases diagnostics must contend with scores of potential pathogens, dozens of clinical syndromes, emerging pathogens, rapid evolution of existing pathogens and their associated resistance mechanisms, and the absence of gold standards in many situations...
March 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28350901/gram-negative-bacterial-infections-research-priorities-accomplishments-and-future-directions-of-the-antibacterial-resistance-leadership-group
#20
Yohei Doi, Robert A Bonomo, David C Hooper, Keith S Kaye, James R Johnson, Cornelius J Clancy, Joshua T Thaden, Martin E Stryjewski, David van Duin
Antimicrobial resistance in pathogenic gram-negative bacteria is one of the most pressing challenges in the field of infectious diseases and is one of 4 key areas of unmet medical need identified by the Antibacterial Resistance Leadership Group (ARLG). The mission of the Gram-Negative Committee is to advance our knowledge of these challenging infections and implement studies to improve patient outcomes. Studies have fallen primarily into 2 broad categories: prospective cohort studies and interventional trials...
March 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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