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Bonomo Robert

Melissa D Barnes, Christopher R Bethel, Jim Alsop, Scott A Becka, Joseph D Rutter, Krisztina M Papp-Wallace, Robert A Bonomo
Pseudomonas aeruginosa is a prevalent and life-threatening Gram-negative pathogen acquired predominantly by immunosuppressed patients during hospitalization. Relebactam, a diazabicyclooctane β-lactamase inhibitor, potently inactivates the Pseudomona s-Derived Cephalosporinase (PDC-3) with a k 2 / K of 41,400 M-1 s-1 and a k off of 0.00095 s-1 Relebactam restored susceptibility to imipenem in 62% of multidrug-resistant (MDR) P. aeruginosa clinical isolates, while only 21% of isolates were susceptible to imipenem-cilastatin alone...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Sandra S Richter, James Karichu, Joshua Otiso, Hillary Van Heule, George Keller, Eric Cober, Laura J Rojas, Andrea M Hujer, Kristine M Hujer, Steve Marshall, Frederico Perez, Susan D Rudin, T Nicholas Domitrovic, Keith S Kaye, Robert Salata, David van Duin, Robert A Bonomo
Colistin and polymyxin B MICs were determined for 106 carbapenem-resistant Klebsiella pneumoniae (CR-Kp) isolates using Sensititre Research Use Only GNX2F plates (Thermo Fisher) and compared to CLSI broth macrodilution (BMD) as the reference method. For colistin, EUCAST breakpoints were applied and testing of isolates with very major (VM) errors was repeated in duplicate by both methods to determine a majority result. Essential agreement (MIC ± one dilution) of GNX2F with the reference method was 97.1% for polymyxin B and 92...
January 9, 2018: Diagnostic Microbiology and Infectious Disease
Federico Perez, Robert A Bonomo
No abstract text is available yet for this article.
February 15, 2018: Lancet Infectious Diseases
Belinda Ostrowsky, Ritu Banerjee, Robert A Bonomo, Sara E Cosgrove, Lisa Davidson, Shira Doron, David N Gilbert, Amanda Jezek, John B Lynch, Edward J Septimus, Javeed Siddiqui, Nicole M Iovine
No abstract text is available yet for this article.
February 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Michiyoshi Nukaga, Krisztina M Papp-Wallace, Tyuji Hoshino, Scott T Lefurgy, Christopher R Bethel, Melissa D Barnes, Elise T Zeiser, J Kristie Johnson, Robert A Bonomo
Ceftazidime-avibactam is a "second generation" β-lactam-β-lactamase inhibitor combination that is effective against Enterobacteriaceae expressing class A extended-spectrum β-lactamases, class A carbapenemases and/or class C cephalosporinases. Knowledge of the interactions of avibactam, a diazabicyclooctane with different β-lactamases is required to anticipate future resistance threats. FOX family β-lactamases possess unique hydrolytic properties with a broadened substrate profile to include cephamycins, partly as a result of an isoleucine at position 346, instead of the conserved asparagine found in most AmpCs...
February 12, 2018: Antimicrobial Agents and Chemotherapy
Ephraim L Tsalik, Robert A Bonomo, Vance G Fowler
Recent advances in the field of infectious disease diagnostics have given rise to a number of host- and pathogen-centered diagnostic approaches. Most diagnostic approaches in contemporary infectious disease focus on pathogen detection and characterization. Host-focused diagnostics have recently emerged and are based on detecting the activation of biological pathways that are highly specific to the type of infecting pathogen (e.g., viral, bacterial, protozoan, fungal). Although this progress is encouraging, it is unlikely that any single diagnostic platform will fully address the clinician's need for actionable data with short turnaround times in all settings...
January 29, 2018: Annual Review of Medicine
Richard R Watkins, George Yendewa, Steven D Burdette, Sophia Horattas, Nairmeen Awad Haller, Caroline Mangira, Robert A Salata, Robert A Bonomo
OBJECTIVES: Spine infections lead to considerable morbidity and high cost to the global health care system. Currently, the evidence for using ceftaroline, an advanced-generation cephalosporin active against methicillin-resistant Staphylococcus aureus (MRSA), in spine infections is limited. METHODS: Describing Infections of the Spine treated with Ceftaroline (DISC) is a multicenter retrospective cohort study that evaluated ceftaroline for treating spine infections...
January 11, 2018: Journal of Global Antimicrobial Resistance
Nadim G El Chakhtoura, Elie Saade, Alina Iovleva, Mohamad Yasmin, Brigid Wilson, Federico Perez, Robert A Bonomo
Non-fermenting Gram-negative bacilli are at the center of the antimicrobial resistance epidemic. Acinetobacter baumannii and Pseudomonas aeruginosa are both designated with a threat level to human health of "serious" by the Centers for Disease Control and Prevention. Two other major non-fermenting Gram-negative bacilli, Stenotrophomonas maltophilia and Burkholderia cepacia complex, while not as prevalent, have devastating effects on vulnerable populations, such as those with cystic fibrosis, as well as immunosuppressed or hospitalized patients...
January 9, 2018: Expert Review of Anti-infective Therapy
Elsa De La Cadena, Adriana Correa, Juan Sebastián Muñoz, Laura J Rojas, Cristhian Hernández-Gómez, Christian Pallares, Federico Perez, Robert A Bonomo, Maria V Villegas
OBJECTIVES: To examine the population structure of representative carbapenem resistant Enterobacter cloacae complex (CR-Ecl) isolates from 8 different Colombian regions and to characterize their asociated β-lactamases. METHODS: Twenty-eight CR-Ecl isolates collected in Colombia between 2009 and 2013 through the Colombian Nosocomial Network were included. Antimicrobial susceptibility testing was performed by broth microdilution. Molecular detection of carbapenemases and extended-spectrum β-lactamases (ESBL), and the presence of Tn4401 was evaluated by PCR and sequencing...
December 20, 2017: Journal of Global Antimicrobial Resistance
Thomas M Harper, Cynthia M June, Magdalena A Taracila, Robert A Bonomo, Rachel A Powers, David A Leonard
OXA-239 is a class D carbapenemase isolated from an Acinetobacter baumannii strain found in Mexico. This enzyme is a variant of OXA-23 with three amino acid substitutions in or near the active site. These substitutions cause OXA-239 to hydrolyze late-generation cephalosporins and the monobactam aztreonam with greater efficiency than OXA-23. OXA-239 activity against the carbapenems doripenem and imipenem is reduced ∼3-fold and 20-fold, respectively. Further analysis demonstrated that two of the substitutions (P225S and D222N) are largely responsible for the observed alteration of kinetic parameters, while the third (S109L) may serve to stabilize the protein...
January 11, 2018: Biochemical Journal
Brandon Eilertson, Eric Cober, Sandra S Richter, Federico Perez, Robert A Salata, Robert C Kalayjian, Richard R Watkins, Yohei Doi, Keith S Kaye, Scott Evans, Vance G Fowler, Robert A Bonomo, Jack DeHovitz, Barry Kreiswirth, David van Duin
Background: Patients on chronic intermittent renal replacement therapy (RRT) are at risk for infection with carbapenem-resistant Enterobacteriaceae (CRE). However, the impact of RRT on outcomes after CRE infections remains to be defined. Here we perform a comparison of outcomes for CRE-infected patients with preserved renal function compared with CRE-infected patients on RRT. Methods: Cases and controls were defined from a prospective cohort of CRE-infected patients from the Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE)...
2017: Open Forum Infectious Diseases
Robert A Bonomo, Eileen M Burd, John Conly, Brandi M Limbago, Laurent Poirel, Julie A Segre, Lars F Westblade
The dramatic increase in the prevalence and clinical impact of infections caused by bacteria producing carbapenemases is a global health concern. Carbapenemase production is especially problematic when encountered in members of the family Enterobacteriaceae. Due to their ability to readily spread and colonize patients in health care environments, preventing the transmission of these organisms is a major public health initiative and coordinated international effort is needed to contain the risk of infection...
October 16, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Emilia Caselli, Chiara Romagnoli, Rachel A Powers, Magdalena A Taracila, Alexandra A Bouza, Hollister C Swanson, Kali A Smolen, Francesco Fini, Bradley J Wallar, Robert A Bonomo, Fabio Prati
Boronic acids are attracting a lot of attention as β-lactamase inhibitors, and in particular, compound S02030 ( Ki = 44 nM) proved to be a good lead compound against ADC-7 ( Acinetobacter-derived cephalosporinase), one of the most significant resistance determinants in A. baumannii. The atomic structure of the ADC-7/S02030 complex highlighted the importance of critical structural determinants for recognition of the boronic acids. Herein, to elucidate the role in recognition of the R2-carboxylate, which mimics the C3 /C4 found in β-lactams, we designed, synthesized, and characterized six derivatives of S02030 (3a)...
March 9, 2018: ACS Infectious Diseases
Alexandra A Bouza, Hollister C Swanson, Kali A Smolen, Alison L VanDine, Magdalena A Taracila, Chiara Romagnoli, Emilia Caselli, Fabio Prati, Robert A Bonomo, Rachel A Powers, Bradley J Wallar
Acinetobacter baumannii is a multidrug resistant pathogen that infects more than 12 000 patients each year in the US. Much of the resistance to β-lactam antibiotics in Acinetobacter spp. is mediated by class C β-lactamases known as Acinetobacter-derived cephalosporinases (ADCs). ADCs are unaffected by clinically used β-lactam-based β-lactamase inhibitors. In this study, five boronic acid transition state analog inhibitors (BATSIs) were evaluated for inhibition of the class C cephalosporinase ADC-7. Our goal was to explore the properties of BATSIs designed to probe the R1 binding site...
March 9, 2018: ACS Infectious Diseases
Natalia Blanco, Anthony D Harris, Clare Rock, J Kristie Johnson, Lisa Pineles, Robert A Bonomo, Arjun Srinivasan, Melinda M Pettigrew, Kerri A Thom
Introduction: Multi-drug resistant (MDR) Acinetobacter baumannii, associated with broad-spectrum antibiotic use, is an important nosocomial pathogen associated with morbidity and mortality. This study aimed to investigate the prevalence of MDR A. baumannii perirectal colonization among adult patients at ICU admission over a 5-year period, and to identify risk factors and outcomes associated with colonization.Methods: A retrospective cohort analysis of patients admitted to the medical (MICU) and surgical intensive care units (SICU) at the University of Maryland Medical Center from May 2005 to September 2009 was performed using perirectal surveillance cultures on admission...
November 13, 2017: Antimicrobial Agents and Chemotherapy
Kim Clarke, Sara Ricciardi, Tim Pearson, Izwan Bharudin, Peter K Davidsen, Michela Bonomo, Daniela Brina, Alessandra Scagliola, Deborah M Simpson, Robert J Beynon, Farhat Khanim, John Ankers, Mark A Sarzynski, Sujoy Ghosh, Addolorata Pisconti, Jan Rozman, Martin Hrabe de Angelis, Chris Bunce, Claire Stewart, Stuart Egginton, Mark Caddick, Malcolm Jackson, Claude Bouchard, Stefano Biffo, Francesco Falciani
Regular endurance training improves muscle oxidative capacity and reduces the risk of age-related disorders. Understanding the molecular networks underlying this phenomenon is crucial. Here, by exploiting the power of computational modeling, we show that endurance training induces profound changes in gene regulatory networks linking signaling and selective control of translation to energy metabolism and tissue remodeling. We discovered that knockdown of the mTOR-independent factor Eif6, which we predicted to be a key regulator of this process, affects mitochondrial respiration efficiency, ROS production, and exercise performance...
November 7, 2017: Cell Reports
Alexander Bergstrom, Andrew Katko, Zach Adkins, Jessica Hill, Zishuo Cheng, Mia Burnett, Hao Yang, Mahesh Aitha, M Rachel Mehaffey, Jennifer S Brodbelt, Kamaleddin H M E Tehrani, Nathaniel I Martin, Robert A Bonomo, Richard C Page, David L Tierney, Walter Fast, Gerard D Wright, Michael W Crowder
Metallo-β-lactamases (MBLs) are a growing threat to the continued efficacy of β-lactam antibiotics. Recently, aspergillomarasmine A (AMA) was identified as an MBL inhibitor, but the mode of inhibition was not fully characterized. Equilibrium dialysis and metal analysis studies revealed that 2 equiv of AMA effectively removes 1 equiv of Zn(II) from MBLs NDM-1, VIM-2, and IMP-7 when the MBL is at micromolar concentrations. Conversely,1 H NMR studies revealed that 2 equiv of AMA remove 2 equiv of Co(II) from Co(II)-substituted NDM-1, VIM-2, and IMP-7 when the MBL/AMA are at millimolar concentrations...
February 9, 2018: ACS Infectious Diseases
Melissa D Barnes, Marisa L Winkler, Magdalena A Taracila, Malcolm G Page, Eric Desarbre, Barry N Kreiswirth, Ryan K Shields, Minh-Hong Nguyen, Cornelius Clancy, Brad Spellberg, Krisztina M Papp-Wallace, Robert A Bonomo
The emergence of Klebsiella pneumoniae carbapenemases (KPCs), β-lactamases that inactivate "last-line" antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. The combination of ceftazidime (CAZ) and avibactam (AVI), a potent β-lactamase inhibitor, represents an attempt to overcome this formidable threat and to restore the efficacy of the antibiotic against Gram-negative bacteria bearing KPCs. CAZ-AVI-resistant clinical strains expressing KPC variants with substitutions in the Ω-loop are emerging...
October 31, 2017: MBio
Nadim G El Chakhtoura, Robert A Bonomo, Robin L P Jump
In older adults, pathophysiologic, clinical, and environmental factors all affect the presentation of infections. We explore how age-related changes influence the manifestation and evaluation of infections in this population. Specific topics include immunosenescence, age-related organ-specific physiologic changes, and frailty. We also describe clinical factors influencing infection risk and presentation in older adults, including temperature regulation, cognitive decline, and malnutrition. Finally, we discuss the influence of the setting in which older adults reside on the clinical evaluation of infection...
December 2017: Infectious Disease Clinics of North America
Rossana Rosa, Susan D Rudin, Laura J Rojas, Andrea M Hujer, Armando Perez-Cardona, Federico Perez, Robert A Bonomo, Octavio Martinez, Lilian M Abbo, Jose F Camargo
Infections with carbapenemase-producing carbapenem-resistant Enterobacteriaceae represent an emergent problem worldwide. Treatment of infections caused by New Delhi metallo-beta-lactamase (NDM)-harboring Enterobacteriaceae is particularly challenging as it frequently involves the use of nephrotoxic agents, which is problematic in kidney transplant recipients and non-renal transplant patients with marginal kidney function. We present two cases of urinary tract infections caused by NDM-harboring Enterobacteriaceae successfully treated with a combination of "double carbapenem" and oral fosfomycin...
February 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
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