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Bonomo Robert

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https://www.readbyqxmd.com/read/28062685/development-and-validation-of-the-increment-esbl-predictive-score-for-mortality-in-patients-with-bloodstream-infections-due-to-extended-spectrum-%C3%AE-lactamase-producing-enterobacteriaceae
#1
Zaira Raquel Palacios-Baena, Belén Gutiérrez-Gutiérrez, Marina De Cueto, Pierluigi Viale, Mario Venditti, Alicia Hernández-Torres, Antonio Oliver, Luis Martínez-Martínez, Esther Calbo, Vicente Pintado, Oriol Gasch, Benito Almirante, José Antonio Lepe, Johann Pitout, Murat Akova, Carmen Peña-Miralles, Mitchell J Schwaber, Mario Tumbarello, Evelina Tacconelli, Julia Origüen, Nuria Prim, German Bou, Helen Giamarellou, Joaquín Bermejo, Axel Hamprecht, Federico Pérez, Manuel Almela, Warren Lowman, Po-Ren Hsueh, Carolina Navarro-San Francisco, Julián Torre-Cisneros, Yehuda Carmeli, Robert A Bonomo, David L Paterson, Álvaro Pascual, Jesús Rodríguez-Baño
BACKGROUND: Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality. METHODS: A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC)...
January 6, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27997706/exploring-the-potential-of-boronic-acids-as-inhibitors-of-oxa-24-40-%C3%AE-lactamase
#2
Josephine P Werner, Joshua M Mitchell, Magdalena A Taracila, Robert A Bonomo, Rachel A Powers
β-lactam antibiotics are crucial to the management of bacterial infections in the medical community. Due to overuse and misuse, clinically significant bacteria are now resistant to many commercially available antibiotics. The most widespread resistance mechanism to β-lactams is the expression of β-lactamase enzymes. To overcome β-lactamase mediated resistance, inhibitors were designed to inactivate these enzymes. However, current inhibitors (clavulanic acid, tazobactam, and sulbactam) for β-lactamases also contain the characteristic β-lactam ring, making them susceptible to resistance mechanisms employed by bacteria...
December 20, 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27974412/clinical-and-pathophysiological-overview-of-acinetobacter-infections-a-century-of-challenges
#3
REVIEW
Darren Wong, Travis B Nielsen, Robert A Bonomo, Paul Pantapalangkoor, Brian Luna, Brad Spellberg
SUMMARYAcinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity...
January 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/27965456/comprehensive-genome-analysis-of-carbapenemase-producing-enterobacter-spp-new-insights-into-phylogeny-population-structure-and-resistance-mechanisms
#4
Kalyan D Chavda, Liang Chen, Derrick E Fouts, Granger Sutton, Lauren Brinkac, Stephen G Jenkins, Robert A Bonomo, Mark D Adams, Barry N Kreiswirth
: Knowledge regarding the genomic structure of Enterobacter spp., the second most prevalent carbapenemase-producing Enterobacteriaceae, remains limited. Here we sequenced 97 clinical Enterobacter species isolates that were both carbapenem susceptible and resistant from various geographic regions to decipher the molecular origins of carbapenem resistance and to understand the changing phylogeny of these emerging and drug-resistant pathogens. Of the carbapenem-resistant isolates, 30 possessed blaKPC-2, 40 had blaKPC-3, 2 had blaKPC-4, and 2 had blaNDM-1 Twenty-three isolates were carbapenem susceptible...
December 13, 2016: MBio
https://www.readbyqxmd.com/read/27957505/bacterial-colonization-and-antibiotic-resistance-in-a-prospective-cohort-of-newborn-infants-during-the-first-year-of-life
#5
Sharon B Meropol, Kurt C Stange, Michael R Jacobs, Judith K Weiss, Saralee Bajaksouzian, Robert A Bonomo
BACKGROUND: Infants are virtually sterile at birth and frequently use antibiotics; our objective was to (1) characterize the longitudinal colonization with bacterial pathogens and associated antibiotic resistance in a cohort of community-dwelling infants in Northeast Ohio and (2) describe longitudinal concurrent antibiotic and daycare exposures. METHODS: For 35 newborns, nasopharyngeal swabs were cultured for Streptococcus pneumoniae, anterior nasal for Staphylococcus aureus, and perirectal for extended-spectrum beta-lactamase (ESBL)-producing Gram-negative enteric bacteria, at 3-month intervals for 12 months...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27940944/colistin-resistance-in-carbapenem-resistant-klebsiella-pneumoniae-laboratory-detection-and-impact-on-mortality
#6
Laura J Rojas, Madiha Salim, Eric Cober, Sandra S Richter, Federico Perez, Robert A Salata, Robert C Kalayjian, Richard R Watkins, Steve Marshall, Susan D Rudin, T Nicholas Domitrovic, Andrea M Hujer, Kristine M Hujer, Yohei Doi, Keith S Kaye, Scott Evans, Vance G Fowler, Robert A Bonomo, David van Duin
BACKGROUND: Polymyxins including colistin are an important "last-line" treatment for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKp). Increasing use of colistin has led to resistance to this cationic antimicrobial peptide. METHODS: A cohort nested within the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRACKLE) was constructed of patients with infection, or colonization with CRKp isolates tested for colistin susceptibility during the study period of December, 2011 to October, 2014...
December 10, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27872073/exploring-the-role-of-the-%C3%AE-loop-in-the-evolution-of-ceftazidime-resistance-in-the-pena-%C3%AE-lactamase-from-burkholderia-multivorans-an-important-cystic-fibrosis-pathogen
#7
Krisztina M Papp-Wallace, Scott A Becka, Magdalena A Taracila, Elise T Zeiser, Julian A Gatta, John J LiPuma, Robert A Bonomo
The unwelcome evolution of resistance to the advanced generation cephalosporin antibiotic, ceftazidime is hindering the effective therapy of Burkholderia cepacia complex (Bcc) infections. Regrettably, Bcc are highly resistant to most antibiotics, including polymyxins; ceftazidime and trimethoprim-sulfamethoxazole are the most effective treatment options. Unfortunately, resistance to ceftazidime is increasing and posing a health threat to populations susceptible to Bcc infection. We found that up to 36% of 146 tested Bcc clinical isolates were non-susceptible to ceftazidime...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27844027/prosthetic-valve-endocarditis-caused-by-bartonella-henselae-a-case-report-of-molecular-diagnostics-informing-nonsurgical-management
#8
Patricia Bartley, Emmanouil Angelakis, Didier Raoult, Rangarajan Sampath, Robert A Bonomo, Robin L P Jump
Identifying the pathogen responsible for culture-negative valve endocarditis often depends on molecular studies performed on surgical specimens. A patient with Ehlers-Danlos syndrome who had an aortic graft, a mechanical aortic valve, and a mitral anulloplasty ring presented with culture-negative prosthetic valve endocarditis and aortic graft infection. Research-based polymerase chain reaction (PCR)/electrospray ionization mass spectrometry on peripheral blood samples identified Bartonella henselae. Quantitative PCR targeting the16S-23S ribonucleic acid intergenic region and Western immunoblotting confirmed this result...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27795336/informing-antibiotic-treatment-decisions-evaluating-rapid-molecular-diagnostics-to-identify-susceptibility-and-resistance-to-carbapenems-against-acinetobacter-spp-in-primers-iii
#9
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
The widespread dissemination of carbapenem-resistant Acinetobacter spp. has created significant therapeutic challenges. At present, rapid molecular diagnostics (RMDs) that can identify this phenotype are not commercially available. Two RMD platforms, PCR combined with electrospray ionization mass spectrometry (PCR/ESI-MS) and molecular beacons (MB), for detecting genes conferring resistance/susceptibility to carbapenems in Acinetobacter spp. were evaluated. An archived collection of 200 clinical Acinetobacter sp...
January 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/27742735/%C3%AE-lactamases-a-focus-on-current-challenges
#10
REVIEW
Robert A Bonomo
β-Lactamases, the enzymes that hydrolyze β-lactam antibiotics, remain the greatest threat to the usage of these agents. In this review, the mechanism of hydrolysis is discussed for both those enzymes that use serine at the active site and those that require divalent zinc ions for hydrolysis. The β-lactamases now include >2000 unique, naturally occurring amino acid sequences. Some of the clinically most important of these are the class A penicillinases, the extended-spectrum β-lactamases (ESBLs), the AmpC cephalosporinases, and the carbapenem-hydrolyzing enzymes in both the serine and metalloenzyme groups...
January 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27741230/treatment-selection-choices-should-not-be-based-on-benefits-or-costs-alone-a-head-to-head-randomized-controlled-trial-of-antiviral-drugs-for-hepatitis-c
#11
Perica Davitkov, Apoorva Krishna Chandar, Amy Hirsch, Anita Compan, Marina G Silveira, Donald D Anthony, Suzanne Smith, Clare Gideon, Robert A Bonomo, Yngve Falck-Ytter
BACKGROUND: Clinicians often face dilemmas with decisions related to formulary choices when two similar drugs are simultaneously available in the market. We studied the comparative safety, effectiveness, and treatment costs of the two first generation direct-acting antiviral agents (DAA), boceprevir and telaprevir as uncertainty existed regarding the drug of choice between these two seemingly equally Hepatitis-C treatment options. METHODS: We randomly assigned 50 patients in an open-label, pragmatic randomized controlled trial (RCT) at a VA Medical Center to either boceprevir or telaprevir in combination with peginterferon and ribavirin, stratified by the presence of cirrhosis and prior treatment experience...
2016: PloS One
https://www.readbyqxmd.com/read/27712635/a-predictive-model-of-mortality-in-patients-with-bloodstream-infections-due-to-carbapenemase-producing-enterobacteriaceae
#12
Belén Gutiérrez-Gutiérrez, Elena Salamanca, Marina de Cueto, Po-Ren Hsueh, Pierluigi Viale, José Ramón Paño-Pardo, Mario Venditti, Mario Tumbarello, George Daikos, Vicente Pintado, Yohei Doi, Felipe Francisco Tuon, Ilias Karaiskos, Isabel Machuca, 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
OBJECTIVE: To develop a score to predict mortality in patients with bloodstream infections (BSIs) due to carbapenemase-producing Enterobacteriaceae (CPE). PATIENTS AND METHODS: A multinational retrospective cohort study (INCREMENT project) was performed from January 1, 2004, through December 31, 2013. Patients with clinically relevant monomicrobial BSIs due to CPE were included and randomly assigned to either a derivation cohort (DC) or a validation cohort (VC)...
October 2016: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/27624957/editorial-commentary-ceftazidime-avibactam-and-carbapenem-resistant-enterobacteriaceae-we-re-gonna-need-a-bigger-boat
#13
EDITORIAL
Brad Spellberg, Robert A Bonomo
No abstract text is available yet for this article.
December 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27623409/bisthiazolidines-a-substrate-mimicking-scaffold-as-an-inhibitor-of-the-ndm-1-carbapenemase
#14
Mariano M González, Magda Kosmopoulou, Maria F Mojica, Valerie Castillo, Philip Hinchliffe, Ilaria Pettinati, Jürgen Brem, Christopher J Schofield, Graciela Mahler, Robert A Bonomo, Leticia I Llarrull, James Spencer, Alejandro J Vila
Pathogenic Gram-negative bacteria resistant to almost all β-lactam antibiotics are a major public health threat. Zn(II)-dependent or metallo-β-lactamases (MBLs) produced by these bacteria inactivate most β-lactam antibiotics, including the carbapenems, which are "last line therapies" for life-threatening Gram-negative infections. NDM-1 is a carbapenemase belonging to the MBL family that is rapidly spreading worldwide. Regrettably, inhibitors of MBLs are not yet developed. Here we present the bisthiazolidine (BTZ) scaffold as a structure with some features of β-lactam substrates, which can be modified with metal-binding groups to target the MBL active site...
November 13, 2015: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27551008/successful-treatment-of-bloodstream-infection-due-to-metallo-%C3%AE-lactamase-producing-stenotrophomonas-maltophilia-in-a-renal-transplant-patient
#15
Maria F Mojica, Christopher P Ouellette, Amy Leber, M Brian Becknell, Monica I Ardura, Federico Perez, Masako Shimamura, Robert A Bonomo, Samuel L Aitken, Samuel A Shelburne
Stenotrophomonas maltophilia is an emerging multidrug-resistant (MDR) opportunistic pathogen for which new antibiotic options are urgently needed. We report our clinical experience treating a 19-year-old renal transplant recipient who developed prolonged bacteremia due to metallo-β-lactamase-producing S. maltophilia refractory to conventional treatment. The infection recurred despite a prolonged course of colistimethate sodium (colistin) but resolved with the use of a novel drug combination with clinical efficacy against the patient's S...
September 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27454763/on-the-path-to-untreatable-infections-colistin-use-in-agriculture-and-the-end-of-last-resort-antibiotics
#16
Richard R Watkins, Tara C Smith, Robert A Bonomo
No abstract text is available yet for this article.
September 2016: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/27419164/metallo-%C3%AE-lactamase-mbl-producing-enterobacteriaceae-in-united-states-children
#17
Latania K Logan, Robert A Bonomo
Metallo-β-lactamases (MBLs) are emerging as the most notable resistance determinants in Enterobacteriaceae. In many cases, the genes encoding MBLs are part of complex, mobile genetic elements that carry other resistance determinants. In the United States, there are increasing reports of MBL-producing Enterobacteriaceae, with New Delhi MBLs (NDMs) accounting for the majority of transmissible MBL infections. Many infections caused by NDM-producing bacteria are associated with international travel and medical tourism...
April 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27303030/cross-class-metallo-%C3%AE-lactamase-inhibition-by-bisthiazolidines-reveals-multiple-binding-modes
#18
Philip Hinchliffe, Mariano M González, Maria F Mojica, Javier M González, Valerie Castillo, Cecilia Saiz, Magda Kosmopoulou, Catherine L Tooke, Leticia I Llarrull, Graciela Mahler, Robert A Bonomo, Alejandro J Vila, James Spencer
Metallo-β-lactamases (MBLs) hydrolyze almost all β-lactam antibiotics and are unaffected by clinically available β-lactamase inhibitors (βLIs). Active-site architecture divides MBLs into three classes (B1, B2, and B3), complicating development of βLIs effective against all enzymes. Bisthiazolidines (BTZs) are carboxylate-containing, bicyclic compounds, considered as penicillin analogs with an additional free thiol. Here, we show both l- and d-BTZ enantiomers are micromolar competitive βLIs of all MBL classes in vitro, with Kis of 6-15 µM or 36-84 µM for subclass B1 MBLs (IMP-1 and BcII, respectively), and 10-12 µM for the B3 enzyme L1...
June 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27208773/antibiotic-resistance-in-the-twenty-first-century-current-concepts-and-future-directions
#19
EDITORIAL
Richard R Watkins, Robert A Bonomo
No abstract text is available yet for this article.
June 2016: Infectious Disease Clinics of North America
https://www.readbyqxmd.com/read/27208767/new-%C3%AE-lactamase-inhibitors-in-the-clinic
#20
REVIEW
Krisztina M Papp-Wallace, Robert A Bonomo
Given the serious medical burden of β-lactamases, many approaches are being used identify candidate agents for β-lactamase inhibition. Here, we review two β-lactam-β-lactamase inhibitor (BL-BLI) combinations, ceftolozane-tazobactam and ceftazidime-avibactam that recently entered the clinic. In addition, we focus on BL-BLI combinations in preclinical development that have demonstrated activity in clinical isolates via susceptibility testing and/or in in vivo models of infection. We highlight only the BLIs that are able to reduce the Clinical Laboratory Standards Institute (CLSI) breakpoints for the BL partner into the susceptible range...
June 2016: Infectious Disease Clinics of North America
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