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Bonomo Robert

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
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
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, polymerase chain reaction 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 spp...
October 26, 2016: Journal of Clinical Microbiology
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...
October 14, 2016: Cold Spring Harbor Perspectives in Medicine
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
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
Brad Spellberg, Robert A Bonomo
No abstract text is available yet for this article.
September 13, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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
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
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
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
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
Richard R Watkins, Robert A Bonomo
No abstract text is available yet for this article.
June 2016: Infectious Disease Clinics of North America
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
Richard R Watkins, Robert A Bonomo
The rapid and ongoing spread of antibiotic resistance poses a serious threat to global public health. The indiscriminant use of antibiotics in agriculture and human medicine along with increasingly connected societies has fueled the distribution of antibiotic-resistant bacteria. These factors together have led to rising numbers of infections caused by multidrug-resistant and pan-resistant bacteria, with increases in morbidity and mortality. This article summarizes the trends in antibiotic resistance, discusses the impact of antibiotic resistance on society, and reviews the use of antibiotics in agriculture...
June 2016: Infectious Disease Clinics of North America
Scott R Evans, Gene Pennello, Norberto Pantoja-Galicia, Hongyu Jiang, Andrea M Hujer, Kristine M Hujer, Claudia Manca, Carol Hill, Michael R Jacobs, Liang Chen, Robin Patel, Barry N Kreiswirth, Robert A Bonomo
The medical community needs systematic and pragmatic approaches for evaluating the benefit-risk trade-offs of diagnostics that assist in medical decision making. Benefit-Risk Evaluation of Diagnostics: A Framework (BED-FRAME) is a strategy for pragmatic evaluation of diagnostics designed to supplement traditional approaches. BED-FRAME evaluates diagnostic yield and addresses 2 key issues: (1) that diagnostic yield depends on prevalence, and (2) that different diagnostic errors carry different clinical consequences...
September 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Lisandro J González, Guillermo Bahr, Toshiki G Nakashige, Elizabeth M Nolan, Robert A Bonomo, Alejandro J Vila
Carbapenems, 'last-resort' β-lactam antibiotics, are inactivated by zinc-dependent metallo-β-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, because those enzymes are readily degraded in their nonmetallated form. However, the New Delhi metallo-β-lactamase (NDM-1) can persist under conditions of metal depletion...
July 2016: Nature Chemical Biology
Pranita D Tamma, Nuntra Suwantarat, Susan D Rudin, Latania K Logan, Patricia J Simner, Laura J Rojas, Maria F Mojica, Karen C Carroll, Robert A Bonomo
We report the first case of a child in the United States infected with an organism producing a Verona Integron-Encoded Metallo-β-Lactamase. This child succumbed to a ventilator-associated pneumonia caused by a Klebsiella pneumoniae producing this resistance mechanism.
September 2016: Journal of the Pediatric Infectious Diseases Society
Belén Gutiérrez-Gutiérrez, Salvador Pérez-Galera, Elena Salamanca, Marina de Cueto, Esther Calbo, Benito Almirante, Pierluigi Viale, Antonio Oliver, Vicente Pintado, Oriol Gasch, Luis Martínez-Martínez, Johann Pitout, Murat Akova, Carmen Peña, José Molina, Alicia Hernández, Mario Venditti, Nuria Prim, Julia Origüen, German Bou, Evelina Tacconelli, Mario Tumbarello, Axel Hamprecht, Helen Giamarellou, Manel Almela, Federico Pérez, Mitchell J Schwaber, Joaquín Bermejo, Warren Lowman, Po-Ren Hsueh, Marta Mora-Rillo, Clara Natera, Maria Souli, Robert A Bonomo, Yehuda Carmeli, David L Paterson, Alvaro Pascual, Jesús Rodríguez-Baño
The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients)...
July 2016: Antimicrobial Agents and Chemotherapy
Juan A Vallejo, Marta Martínez-Guitián, Juan C Vázquez-Ucha, Concepción González-Bello, Margarita Poza, John D Buynak, Christopher R Bethel, Robert A Bonomo, German Bou, Alejandro Beceiro
OBJECTIVES: Carbapenemases are the most important mechanism responsible for carbapenem resistance in Enterobacteriaceae. Among carbapenemases, OXA-48 presents unique challenges as it is resistant to β-lactam inhibitors. Here, we test the capacity of the compound LN-1-255, a 6-alkylidene-2'-substituted penicillanic acid sulfone, to inhibit the activity of the carbapenemase OXA-48. METHODS: The OXA-48 gene was cloned and expressed in Klebsiella pneumoniae and Escherichia coli in order to obtain MICs in the presence of inhibitors (clavulanic acid, tazobactam and sulbactam) and LN-1-255...
August 2016: Journal of Antimicrobial Chemotherapy
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