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Author Robert A Bonomo

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Structural and biochemical characterization of the novel CTX-M-151 extended-spectrum β-lactamase and its inhibition by Avibactam.

Barbara Ghiglione, María Margarita Rodríguez, Florencia Brunetti, Krisztina M Papp-Wallace, Ayumi Yoshizumi, Yoshikazu Ishii, Robert A Bonomo, Gabriel Gutkind, Sebastián Klinke, Pablo Power,

The diazabicyclooctane (DBO) inhibitor, avibactam (AVI), reversibly inactivates most serine-β-lactamases including the CTX-M β-lactamases. Currently, more than 230 CTX-M unique members distributed in five clusters with less than 5% amino acid sequence divergence within each group are described. Recently, a variant named as CTX-M-151 was isolated from a <i>Salmonella</i> Choleraesuis ... Read more >>

Antimicrob Agents Chemother (Antimicrobial agents and chemotherapy)
[2021, :]

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A Multicentered Study of the Clinical and Molecular Epidemiology of TEM- and SHV-type Extended-Spectrum Beta-Lactamase Producing Enterobacterales Infections in Children.

Latania K Logan, Jared R Rispens, Rachel L Medernach, T Nicholas Domitrovic, Andrea M Hujer, Steven H Marshall, Susan D Rudin, Nadia K Qureshi, Xiaotian Zheng, Mary K Hayden, Robert A Weinstein, Robert A Bonomo,

<h4>Background</h4>Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales-(Ent) infections are increasing in pediatrics. Before CTX-M ESBL emerged, the most common infection-associated ESBL genes were TEM and SHV-type ESBLs. We sought to define the current epidemiology of Ent infections in children due to blaTEM and blaSHV (TEM-SHV-Ent).<h4>Methods</h4>A retrospective case-control analysis of children with TEM-SHV-Ent infections ... Read more >>

Pediatr Infect Dis J (The Pediatric infectious disease journal)
[2021, 40(1):39-43]

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Natural variants modify Klebsiella pneumoniae carbapenemase (KPC) acyl-enzyme conformational dynamics to extend antibiotic resistance.

Catherine L Tooke, Philip Hinchliffe, Robert A Bonomo, Christopher J Schofield, Adrian J Mulholland, James Spencer,

Class A serine β-lactamases (SBLs) are key antibiotic resistance determinants in Gram-negative bacteria. SBLs neutralize β-lactams via a hydrolytically labile covalent acyl-enzyme intermediate. Klebsiella pneumoniae carbapenemase (KPC) is a widespread SBL that hydrolyzes carbapenems, the most potent β-lactams; known KPC variants differ in turnover of expanded-spectrum oxyimino-cephalosporins (ESOCs), e.g. cefotaxime ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2020, :]

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Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR MAT): A Framework for Assessing Antibiotic Selection Strategies in the Presence of Drug Resistance.

Brigid M Wilson, Yunyun Jiang, Robin L P Jump, Roberto Viau Colindres, Federico Perez, Robert A Bonomo, Scott R Evans,

The complexities of antibiotic resistance mean that successful stewardship must consider both the effectiveness of a given antibiotic and the spectrum of that therapy to minimize imposing further selective pressure. To meet this challenge, we propose the Desirability of Outcome Ranking approach for the Management of Antimicrobial Therapy (DOOR MAT), ... Read more >>

Clin Infect Dis (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America)
[2020, :]

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The Ongoing Threat of Antimicrobial Resistance.

Richard R Watkins, Robert A Bonomo,

Infect Dis Clin North Am (Infectious disease clinics of North America)
[2020, 34(4):xiii-xiv]

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Structural Insights into Inhibition of the Acinetobacter-Derived Cephalosporinase ADC-7 by Ceftazidime and Its Boronic Acid Transition State Analog.

Brandy N Curtis, Kali A Smolen, Sara J Barlow, Emilia Caselli, Fabio Prati, Magdalena A Taracila, Robert A Bonomo, Bradley J Wallar, Rachel A Powers,

Extended-spectrum class C β-lactamases have evolved to rapidly inactivate expanded-spectrum cephalosporins, a class of antibiotics designed to be resistant to hydrolysis by β-lactamase enzymes. To better understand the mechanism by which <i><u>A</u>cinetobacter</i>-<u>d</u>erived <u>c</u>ephalosporinase-7 (ADC-7), a chromosomal AmpC enzyme, hydrolyzes these molecules, we determined the X-ray crystal structure of ADC-7 in ... Read more >>

Antimicrob Agents Chemother (Antimicrobial agents and chemotherapy)
[2020, 64(12):]

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A comprehensive and contemporary "snapshot" of β-lactamases in carbapenem resistant Acinetobacter baumannii.

Andrea M Hujer, Kristine M Hujer, David A Leonard, Rachel A Powers, Bradley J Wallar, Andrew R Mack, Magdalena A Taracila, Philip N Rather, Paul G Higgins, Fabio Prati, Emilia Caselli, Steven H Marshall, Thomas Clarke, Christopher Greco, Pratap Venepally, Lauren Brinkac, Barry N Kreiswirth, Derrick E Fouts, Robert A Bonomo, ,

Successful treatment of Acinetobacter baumannii infections require early and appropriate antimicrobial therapy. One of the first steps in this process is understanding which β-lactamase (bla) alleles are present and in what combinations. Thus, we performed WGS on 98 carbapenem-resistant A. baumannii (CR Ab). In most isolates, an acquired bla<sub>OXA</sub> carbapenemase ... Read more >>

Diagn Microbiol Infect Dis (Diagnostic microbiology and infectious disease)
[2020, 99(2):115242]

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Infectious Diseases Society of America Antimicrobial Resistant Treatment Guidance: Gram-Negative Bacterial Infections.

Pranita D Tamma, Samuel L Aitken, Robert A Bonomo, Amy J Mathers, David van Duin, Cornelius J Clancy,

<h4>Background</h4>This guidance document provides recommendations to clinicians for the treatment of infections caused by extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Antimicrobial resistant infections are commonly encountered in United States hospitals, result in significant morbidity and mortality.<h4>Methods</h4>A panel of six infectious ... Read more >>

Clin Infect Dis (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America)
[2020, :]

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1642. A Novel β-lactamase Inhibitor (Durlobactam, DUR) and β-Lactams Enhance Susceptibility Against Multidrug-Resistant (MDR) Mycobacterium abscessus (Mab)

Khalid M Dousa, Sebastian G Kurz, Christopher Bethel, Alita Miller, Robert A Bonomo,

Abstract <h4>Background</h4> Mab is a MDR nontuberculous mycobacterium that causes lung infections in patients with structural lung disease. Mab harbors a chromosomally encoded class A β-lactamase, BlaMab, able to hydrolyze penicillins, cephalosporins and carbapenems. L,D- and D,D-transpeptidases (L,D TP and D,D TP) shape peptidoglycan (PG) synthesis and contribute to cell ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2020, 7(Suppl 1):S810-S811]

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1325. Things that go Bump in the Night: Combating Klebsiella pneumoniae co-producing New Delhi metallo-beta-lactamase (NDM) and Mobile Colistin Resistance (MCR)

Nicholas M Smith, Liang Chen, Katie Rose Boissonneault, Thomas Lodise, Patricia N Holden, Juergen B Bulitta, Robert A Bonomo, Barry N Kreiswirth, Brian T Tsuji,

Abstract <h4>Background</h4> The scourge of MBLs among Gram negatives, such New Delhi Metallo-beta-lactamase-producing Klebsiella pneumoniae, has resulted in an overwhelming need for new treatmens. Worryingly, additional acquisition of plasmid-mediated polymyxin resistance through the mcr gene can produce strains resistant to all last line agents. The novel combination of aztreonam (ATM, ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2020, 7(Suppl 1):S673-S673]

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1250. Novel Boronic Acid Transition State Analogs (BATSI) with in vitro inhibitory activity against class A, B and C β-lactamases

Maria F Mojica, Christopher Bethel, Emilia Caselli, Magdalena A Taracila, Fabio Prati, Robert A Bonomo,

Abstract <h4>Background</h4> Catalytic mechanisms of serine β-lactamases (SBL; classes A, C and D) and metallo-β-lactamases (MBLs) have directed divergent strategies towards inhibitor design. SBL inhibitors act as high affinity substrates that -as in BATSIs- form a reversible, dative covalent bond with the conserved active site Ser. MBL inhibitors bind the ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2020, 7(Suppl 1):S643-S643]

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1444. Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia Anopheles

Mohamad Yasmin, Steven Marshall, Emma Marshall, Anna Cmolik, Helen Boucher, Alejandro Vila, Robert A Bonomo,

Abstract <h4>Background</h4> A 60-year-old woman with acute myeloid leukemia developed fever and cough post induction chemotherapy. Meropenem and vancomycin were administered as empiric therapy. A bloodstream infection due to resistant E. meningoseptica was initially identified. Ceftazidime-avibactam and aztreonam (ATM) were next administered. Minocycline and trimethoprim/sulfamethoxazole (TMP/SMX) were added as the ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2020, 7(Suppl 1):S725-S725]

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1256. In Vivo Activity and Structural Characterization of a New Generation γ-Lactam Siderophore Antibiotic Against Multidrug-Resistant Gram-Negative Bacteria and Acinetobacter spp

Joel Goldberg, Christopher Bethel, Andrea M Hujer, Steven Marshall, Magdalena A Taracila, Krisztina M Papp-Wallce, Vijay Kumar, Focco van den Akker, Mark Plummer, Robert A Bonomo,

Abstract <h4>Background</h4> Multidrug-resistant (MDR) A. baumannii presents a critical need for innovative antibacterial development. We have identified a new series of γ-lactam (oxopyrazole) antibiotics that target penicillin binding proteins (PBPs) and incorporate a siderophore moiety to facilitate periplasmic uptake. YU253911, an advanced iteration of this class shows potent in vitro ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2020, 7(Suppl 1):S645-S645]

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1437. Biochemical characterization of L1 and L2 β-lactamases from clinical isolates of Stenotrophomonas maltophilia

Maria F Mojica, Joseph Rutter, Magdalena A Taracila, Krisztina M Papp-Wallce, James Spencer, Alejandro J Vila, Robert A Bonomo,

Abstract <h4>Background</h4> Stenotrophomonas maltophilia is a Gram-negative, non-fermenting opportunistic pathogen. Two β-lactamases provide intrinsic resistance to β-lactams: a class B Metallo- β-lactamase L1, and a class A serine β-lactamase (SβL) L2. Recently, we described novel variants of the L1 and L2 in a collection of clinical S. maltophilia isolates collected ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2020, 7(Suppl 1):S723-S723]

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Overview: The Ongoing Threat of Antimicrobial Resistance.

Richard R Watkins, Robert A Bonomo,

The effectiveness of antibiotics continues to erode because of the relentless spread of antimicrobial resistance (AMR). Public and private foundations, professional organizations, and international health agencies recognize the threat posed by AMR and have issued calls for action. One of the main drivers of AMR is overprescription of antibiotics, both ... Read more >>

Infect Dis Clin North Am (Infectious disease clinics of North America)
[2020, 34(4):649-658]

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Drug-Resistant Tuberculosis: A Glance at Progress and Global Challenges.

Khalid M Dousa, Sebastian G Kurz, Charles M Bark, Robert A Bonomo, Jennifer J Furin,

Multidrug-resistant Mycobacterium tuberculosis remains a major public health threat; its management poses a significant economic burden. Treatment requires a programmatic approach with access to laboratory services, second-line medications, and adequate clinical resources. In recent years, we have seen rapid developments in diagnostic techniques with whole genome sequencing-based drug susceptibility prediction ... Read more >>

Infect Dis Clin North Am (Infectious disease clinics of North America)
[2020, 34(4):863-886]

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Efflux pumps as interventions to control infection caused by drug-resistance bacteria.

Nabeela Farhat, Abid Ali, Robert A Bonomo, Asad U Khan,

Antibiotic resistance has become a global concern for healthcare workers and physicians. Efflux pumps are one of the major mechanisms of resistance. Hence, we describe examples of natural efflux pump inhibitors used to combat antibiotic resistance. ... Read more >>

Drug Discov Today (Drug discovery today)
[2020, 25(12):2307-2316]

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AbGRI4, a novel antibiotic resistance island in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates.

Agnes P Chan, Yongwook Choi, Thomas H Clarke, Lauren M Brinkac, Richard C White, Michael R Jacobs, Robert A Bonomo, Mark D Adams, Derrick E Fouts,

<h4>Objectives</h4>To investigate the genomic context of a novel resistance island (RI) in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates and global isolates.<h4>Methods</h4>Using a combination of long and short reads generated from the Oxford Nanopore and Illumina platforms, contiguous chromosomes and plasmid sequences were determined. BLAST-based analysis was used to identify the ... Read more >>

J Antimicrob Chemother (The Journal of antimicrobial chemotherapy)
[2020, 75(10):2760-2768]

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1572. Combination Cefuroxime and Sulopenem is active in vitro against Mycobacterium abscessus

Khalid M Dousa, David C Nguyen, Sebastian G Kurz, Magdalena A Taracila, Christopher Bethel, Robert A Bonomo,

Abstract <h4>Background</h4> Mycobacterium abscessus (Mab) is a highly drug-resistant nontuberculous mycobacteria (NTM). Efforts to discover new treatments for Mab infections are accelerating with a focus on cell wall synthesis proteins (L, D-transpeptidases, LdtMab1-5, and D, D-carboxypeptidase) that are targeted by combination β-lactam antibiotics. The US Food and Drug Administration (FDA) ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2020, 7(Suppl 1):S785-S785]

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158. Intra- and Inter-hospital Epidemiology of Carbapenem-resistant klebsiella Pneumoniae in US Hospitals

Courtney Luterbach, Liang Chen, Blake Hanson, Michelle Earley, Lauren Komarow, Gregory Weston, Eric Cober, Julia Garcia Diaz, Keith S Kaye, W Charles Huskins, Jason C Gallagher, Robert A Bonomo, Cesar A Arias, Barry N Kreiswirth, David van Duin,

Abstract <h4>Background</h4> Carbapenem-resistant Enterobacterales (CRE) and specifically Klebsiella pneumoniae (CRKp) are a global threat. CRE rapidly spreading in a healthcare network may infect a distinct patient cohort or have higher virulence. We determined the impact of cluster assignment of CRKp on transmission dynamics and clinical outcomes. <h4>Methods</h4> CRACKLE-2 is a ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2020, 7(Suppl 1):S208-S209]

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1445. Deciphering the Role of the Y221H Ω-loop Substitution in Pseudomonas-derived Cephalosporinase (PDC) in Cephalosporin Resistance

Andrew R Mack, Melissa D Barnes, Magdalena A Taracila, Maria F Mojica, Vijay Kumar, Joseph Rutter, Focco van den Akker, Malcolm Page, Shozeb Haider, Robert A Bonomo,

Abstract <h4>Background</h4> Antimicrobial resistance is a major global health threat. Pseudomonas aeruginosa is a leading cause of nosocomial infections and a key opportunistic pathogen in cystic fibrosis. Multidrug resistant strains are classified as a “serious threat” by the CDC. Pseudomonas-derived cephalosporinase (PDC) is largely responsible for β-lactam antibiotic resistance in ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2020, 7(Suppl 1):S725-S726]

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1458. Uncharted territories: applying “precision medicine” to understand the treacherous landscape of extensively and multidrug resistant (XDR and MDR) Pseudomonas aeruginosa in a patient with cystic fibrosis and lung transplantation

Laura J Rojas, Mohamad Yasmin, Jacquelynn Benjamino, Steven Marshall, Kailynn DeRonde, Nikhil Krishnan, Federico Perez, Andrew Colin, Monica Cardenas, Octavio Martinez, Armando Perez-Cardona, Daniel Rhoads, Michael Jacobs, Jacob Scott, Mark D Adams, Lilian M Abbo, Lilian M Abbo, Robert A Bonomo,

Abstract <h4>Background</h4> Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with cystic fibrosis (CF). Herein, we describe our experience managing a young woman suffering from CF with XDR P. aeruginosa who underwent lung transplantation. We highlight the contemporary difficulties reconciling the clinical, microbiological, and genetic ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2020, 7(Suppl 1):S731-S731]

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Reply to Vena et al.

Jason M Pogue, Keith S Kaye, Robert A Bonomo, Federico Perez,

Clin Infect Dis (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America)
[2020, 71(7):1801-1802]

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Resistance to Novel β-Lactam-β-Lactamase Inhibitor Combinations: The "Price of Progress".

Krisztina M Papp-Wallace, Andrew R Mack, Magdalena A Taracila, Robert A Bonomo,

Significant advances were made in antibiotic development during the past 5 years. Novel agents were added to the arsenal that target critical priority pathogens, including multidrug-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales. Of these, 4 novel β-lactam-β-lactamase inhibitor combinations (ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam) reached clinical approval in the United States. With ... Read more >>

Infect Dis Clin North Am (Infectious disease clinics of North America)
[2020, 34(4):773-819]

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Longitudinal Colonization With Streptococcus pneumoniae During the First Year of Life in a Healthy Newborn Cohort.

Sharon B Meropol, Michael R Jacobs, Kurt C Stange, Saralee Bajaksouzian, Robert A Bonomo,

BACKGROUND:The objective of this study was to characterize longitudinal colonization with Streptococcus pneumoniae during the first year of life within a community newborn infant cohort, and assess the relationship between antibiotic exposure and colonization with antibiotic-resistant organisms. METHODS:During April 2013-February 2014, 326 infants were enrolled from an urban academic hospital ... Read more >>

J Pediatric Infect Dis Soc (Journal of the Pediatric Infectious Diseases Society)
[2020, 9(4):442-448]

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