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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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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)
[2021, 99(2):115242]

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Monitoring Ceftazidime-Avibactam and Aztreonam Concentrations in the Treatment of a Bloodstream Infection Caused by a Multidrug-Resistant Enterobacter sp. Carrying Both Klebsiella pneumoniae Carbapenemase-4 and New Delhi Metallo-β-Lactamase-1.

Mohamad Yasmin, Derrick E Fouts, Michael R Jacobs, Hanan Haydar, Steven H Marshall, Richard White, Roshan D'Souza, Thomas P Lodise, Daniel D Rhoads, Andrea M Hujer, Laura J Rojas, Claudia Hoyen, Federico Perez, Amy Edwards, Robert A Bonomo,

In an infection with an Enterobacter sp. isolate producing Klebsiella pneumoniae Carbapenemase-4 and New Delhi Metallo-β-Lactamase-1 in the United States, recognition of the molecular basis of carbapenem resistance allowed for successful treatment by combining ceftazidime-avibactam and aztreonam. Antimicrobial synergy testing and therapeutic drug monitoring assessed treatment adequacy. ... Read more >>

Clin Infect Dis (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America)
[2020, 71(4):1095-1098]

Cited: 2 times

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A Ceftazidime-Avibactam-Resistant and Carbapenem-Susceptible Klebsiella pneumoniae Strain Harboring bla KPC-14 Isolated in New York City.

Siqiang Niu, Kalyan D Chavda, Jie Wei, Chunhong Zou, Steven H Marshall, Puneet Dhawan, Deqiang Wang, Robert A Bonomo, Barry N Kreiswirth, Liang Chen,

Ceftazidime-avibactam is a potent antibiotic combination against <i>Klebsiella pneumoniae</i> carbapenemase (KPC)-producing <i>Enterobacteriaceae</i> Here, we describe a unique ceftazidime-avibactam-resistant and carbapenem-susceptible <i>K. pneumoniae</i> strain harboring a novel <i>bla</i> <sub>KPC-14</sub> variant. This strain was isolated from a New York City patient in 2003, which predates the introduction of avibactam. Despite resistance to ... Read more >>

mSphere (mSphere)
[2020, 5(4):]

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A γ-Lactam Siderophore Antibiotic Effective against Multidrug-Resistant Gram-Negative Bacilli.

Joel A Goldberg, Ha Nguyen, Vijay Kumar, Elizabeth J Spencer, Denton Hoyer, Emma K Marshall, Anna Cmolik, Margaret O'Shea, Steven H Marshall, Andrea M Hujer, Kristine M Hujer, Susan D Rudin, T Nicholas Domitrovic, Christopher R Bethel, Krisztina M Papp-Wallace, Latania K Logan, Federico Perez, Michael R Jacobs, David van Duin, Barry M Kreiswirth, Robert A Bonomo, Mark S Plummer, Focco van den Akker,

Treatment of multidrug-resistant Gram-negative bacterial pathogens represents a critical clinical need. Here, we report a novel γ-lactam pyrazolidinone that targets penicillin-binding proteins (PBPs) and incorporates a siderophore moiety to facilitate uptake into the periplasm. The MIC values of γ-lactam YU253434, 1, are reported along with the finding that 1 is ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, 63(11):5990-6002]

Cited: 1 time

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Carbapenem-Susceptible Klebsiella pneumoniae and Escherichia coli Isolates Carrying a Truncated KPC Carbapenemase: a Challenge for Rapid Molecular Diagnostics.

Hossein Salimnia, Jennifer Veltman, Pranatharthi H Chandrasekar, Jason M Pogue, Ryan Mynatt, Tanaz Salimnia, Steven H Marshall, Andrea M Hujer, Robert A Bonomo,

J Clin Microbiol (Journal of clinical microbiology)
[2020, 58(3):]

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A Single Salt Bridge in VIM-20 Increases Protein Stability and Antibiotic Resistance under Low-Zinc Conditions.

Zishuo Cheng, Ben A Shurina, Christopher R Bethel, Pei W Thomas, Steven H Marshall, Caitlyn A Thomas, Kundi Yang, Robert L Kimble, Jonathan S Montgomery, Matthew G Orischak, Callie M Miller, Jordan L Tennenbaum, Jay C Nix, David L Tierney, Walter Fast, Robert A Bonomo, Richard C Page, Michael W Crowder,

To understand the evolution of Verona integron-encoded metallo-β-lactamase (VIM) genes (<i>bla</i> <sub>VIM</sub>) and their clinical impact, microbiological, biochemical, and structural studies were conducted. Forty-five clinically derived VIM variants engineered in a uniform background and expressed in <i>Escherichia coli</i> afforded increased resistance toward all tested antibiotics; the variants belonging to the ... Read more >>

mBio (mBio)
[2019, 10(6):]

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594. A Multi-Centered Study of the Clinical and Molecular Epidemiology of AmpC Cephalosporinase-Producing (AmpC) Enterobacteriaceae (Ent) Infections in Children

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

Abstract Background AmpC producing Ent are an important cause of multidrug-resistant (MDR) infections in pediatrics. Since most AmpC Ent studies have been conducted in adults, we characterized the molecular epidemiology of AmpC Ent strains with transmissible resistance and identified factors associated with AmpC Ent infections in children. Methods A case–control ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2019, 6(Suppl 2):S280-S280]

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Identification of four patients with colistin-resistant Escherichia coli containing the mobile colistin resistance mcr-1 gene from a single health system in Michigan.

Oryan Henig, Laura J Rojas, Michael A Bachman, Susan D Rudin, Brenda M Brennan, Marty K Soehnlen, Kelly L Jones, John P Mills, Carey R Dombecki, Amanda M Valyko, Steven H Marshall, Robert A Bonomo, Keith S Kaye, Laraine Washer,

Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). ... Read more >>

Infect Control Hosp Epidemiol (Infection control and hospital epidemiology)
[2019, 40(9):1059-1062]

Cited: 1 time

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Community Origins and Regional Differences Highlight Risk of Plasmid-mediated Fluoroquinolone Resistant Enterobacteriaceae Infections in Children.

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

<h4>Background</h4>Fluoroquinolones are uncommonly prescribed in children, yet pediatric multidrug resistant (MDR) enterobacteriaceae (Ent) infections often reveal fluoroquinolone resistance (FQR). We sought to define the molecular epidemiology of FQR and MDR-Ent in children.<h4>Methods</h4>A case-control analysis of children with MDR-Ent infections at 3 Chicago hospitals was performed. Cases were children with third-generation ... Read more >>

Pediatr Infect Dis J (The Pediatric infectious disease journal)
[2019, 38(6):595-599]

Cited: 2 times

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A Multi-Centered Case-Case-Control Study of Factors Associated With Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Infections in Children and Young Adults.

Latania K Logan, David C Nguyen, Felicia A Scaggs Huang, Nadia K Qureshi, Angella Charnot-Katsikas, Allison H Bartlett, Xiaotian Zheng, Andrea M Hujer, T Nicholas Domitrovic, Steven H Marshall, Robert A Bonomo, Robert A Weinstein,

<h4>Background</h4>Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae (KPC-CRE) are multidrug-resistant organisms causing morbidity and mortality worldwide. KPC-CRE prevalence is increasing in pediatric populations, though multi-centered data are lacking. Identifying risk factors for KPC-CRE infection in children and classifying genotypes is a priority in this vulnerable population.<h4>Methods</h4>A case-case-control study of patients (0-22 years) ... Read more >>

Pediatr Infect Dis J (The Pediatric infectious disease journal)
[2019, 38(5):490-495]

Cited: 3 times

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The Clinical and Molecular Epidemiology of CTX-M-9 Group Producing Enterobacteriaceae Infections in Children.

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

<h4>Introduction</h4>The pandemic of extended-spectrum beta-lactamase-(ESBL)-producing Enterobacteriaceae (Ent) is strongly linked to the dissemination of CTX-M-type-ESBL-Ent. We sought to define the epidemiology of infections in children due to an emerging resistance type, CTX-M-9-group-producing-Ent (CTX-M-9-grp-Ent).<h4>Methods</h4>A retrospective matched case-control analysis of children with CTX-M-9-grp-Ent infections who received medical care at three Chicago area ... Read more >>

Infect Dis Ther (Infectious diseases and therapy)
[2019, 8(2):243-254]

Cited: 2 times

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2336. Resistance Mechanisms and Factors Associated With CTX-M-9 Group Extended-Spectrum β-Lactamase (ESBL)-Producing Infections in Children.

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

AbstractBackgroundThere is an increasing incidence of extended-spectrum β-lactamase (ESBL) producing infections in children. However, most studies focus only on CTX-M-1 group (CTX-M-15). We sought to define the epidemiology of the CTX-M-9 group (CTX-M-9) producing infections in children to devise more effective treatment and prevention strategies.MethodsA case–control study of ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2018, 5(Suppl 1):S694-S694]

Cited: 0 times

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2560. Multispecies Outbreak of KPC-2 Producing in a Chilean Pediatric Hospital.

Laura J Rojas, Steven H Marshall, Lina M Rivas, Maria Spencer, Joseph Rutter, Michael R Jacobs, Federico Perez, Paulina Coria, Francisca Valdivieso, Rafael Araos Bralic, Jose M Munita, Robert A Bonomo,

AbstractBackgroundCarbapenem-resistant (CRE) are a critical global health problem. We detected a surge of CRE cases in a pediatric hospital in Chile, a country with a low endemicity of KPC-producing organisms. Herein, we describe the molecular epidemiology of this outbreak.MethodsCRE isolates from clinical specimens and surveillance rectal swabs (obtained using ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2018, 5(Suppl 1):S70-S71]

Cited: 0 times

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2395. Mechanism-Based-Susceptibility Testing (MBST) Using Disc Diffusion Assays (DDA) to Guide Treatment of Multidrug- and Extensively Drug-Resistant Pseudomonas aeruginosa (MDR-XDR-Pa) in a Cystic Fibrosis (CF) Lung Transplant Recipient; Are We Ready for Combination Therapy vs. MDR-XDR-Pa?

Lilian M Abbo, Mohamad Yasmin, Steven H Marshall, Federico Perez, Mónica Corzo-Pedrosa, Jose F Camargo, Jacques Simkins, Laura Aragon, Shweta Anjan, Michele I Morris, Nicolas Brozzi, Mathias Loebe, Jesse Fulmer, Neeraj Sinha, Octavio Martinez, Armando Perez-Cardona, Andrew Colin, Christina Cloke, Robert A Bonomo,

Abstract <h4>Background</h4> Lung infections with MDR-XDR-Pa in patients with CF are challenging due to the emergence of antibiotic resistance. We applied MBST with DDA to guide combination antibiotic therapy in an 18-year-old woman with CF. We investigated if this approach can assist in choosing effective regimens. <h4>Methods</h4> Consecutive Pa respiratory ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2018, 5(Suppl 1):S714-S714]

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700. Identification and Whole-Genome Sequencing (WGS) of Meropenem-Vaborbactam (MV) Resistant Klebsiella pneumoniae (MVRKP) Among Patients Without Prior Exposure to MV: Collateral Damage

Mohamad Yasmin, Liang Chen, Steven H Marshall, Barry N Kreiswirth, Federico Perez, Robert A Bonomo,

Abstract Background MV is a newly approved β-lactam/β-lactamase inhibitor combination (BLIC) for the treatment of complicated urinary tract infections (cUTI). Vaborbactam is a cyclic boronic acid BLI that was mainly developed as a potent inhibitor of KPC carbapenemases and other Ambler class A&C enzymes. Vaborbactam is inactive against metallo-β-lactamases (MBL) ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2018, 5(Suppl 1):S252-S252]

Cited: 0 times

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Correction to Dipicolinic Acid Derivatives as Inhibitors of New Delhi Metallo-β-lactamase-1.

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,

J Med Chem (Journal of medicinal chemistry)
[2018, 61(14):6400]

Cited: 0 times

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Sequence heterogeneity of the PenA carbapenemase in clinical isolates of Burkholderia multivorans.

Scott A Becka, Elise T Zeiser, Steven H Marshall, Julian A Gatta, Kevin Nguyen, Indresh Singh, Chris Greco, Granger G Sutton, Derrick E Fouts, John J LiPuma, Krisztina M Papp-Wallace,

Multidrug-resistant gram-negative pathogens are a significant health threat. Burkholderia spp. encompass a complex subset of gram-negative bacteria with a wide range of biological functions that include human, animal, and plant pathogens. The treatment of infections caused by Burkholderia spp. is problematic due to their inherent resistance to multiple antibiotics. The ... Read more >>

Diagn Microbiol Infect Dis (Diagnostic microbiology and infectious disease)
[2018, 92(3):253-258]

Cited: 3 times

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Emergence of Resistance to Colistin During the Treatment of Bloodstream Infection Caused by Klebsiella pneumoniae Carbapenemase-Producing Klebsiella pneumoniae.

Anubhav Kanwar, Steven H Marshall, Federico Perez, Myreen Tomas, Michael R Jacobs, Andrea M Hujer, T Nicholas Domitrovic, Susan D Rudin, Laura J Rojas, Barry N Kreiswirth, Liang Chen, Miguel Quinones-Mateu, David van Duin, Robert A Bonomo, ,

We report the emergence of colistin resistance in <i>Klebsiella pneumoniae</i> carbapenemase (KPC)-producing <i>Klebsiella pneumoniae</i> after 8 days of colistin-based therapy, resulting in relapse of bloodstream infection and death. Disruption of the <i>mgrB</i> gene by insertion of a mobile genetic element was found to be the mechanism, which was replicated in ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2018, 5(4):ofy054]

Cited: 0 times

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Nosocomial Outbreak of Extensively Drug-Resistant Acinetobacter baumannii Isolates Containing blaOXA-237 Carried on a Plasmid.

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 mainstays for treating infections caused by <i>Acinetobacter baumannii</i>, especially in the Northwest United States, where carbapenem-resistant <i>A. baumannii</i> remains relatively rare. However, between June 2012 and October 2014, an outbreak of carbapenem-resistant <i>A. baumannii</i> occurred in 16 patients from five health care facilities in the ... Read more >>

Antimicrob Agents Chemother (Antimicrobial agents and chemotherapy)
[2017, 61(11):]

Cited: 5 times

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Failure to Communicate: Transmission of Extensively Drug-Resistant bla OXA-237-Containing Acinetobacter baumannii-Multiple Facilities in Oregon, 2012-2014.

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 ... Read more >>

Infect Control Hosp Epidemiol (Infection control and hospital epidemiology)
[2017, 38(11):1335-1341]

Cited: 6 times

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Dipicolinic Acid Derivatives as Inhibitors of New Delhi Metallo-β-lactamase-1.

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 ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2017, 60(17):7267-7283]

Cited: 22 times

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A Multicenter Study of the Clinical and Molecular Epidemiology of TEM- and SHV-type Extended- Spectrum β-Lactamase producing (ESBL) () Infections in Children.

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

AbstractBackgroundESBL infections are increasingly prevalent in the pediatric population; however, most ESBL studies have focused on adults and/or CTX-M-type strains. We sought to characterize the molecular epidemiology of ESBL strains and to identify factors associated with TEM- and SHV-type ESBL (TEMSHV ) infections in children.MethodsA case–control ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2017, 4(Suppl 1):S679-S679]

Cited: 0 times

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NDM-5 and OXA-181 Beta-Lactamases, a Significant Threat Continues To Spread in the Americas.

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 <i>Klebsiella pneumoniae</i> ST147 isolate harboring <i>bla</i><sub>NDM-5</sub> and <i>bla</i><sub>OXA-181</sub> from a young man who underwent abdominal surgery in India. <i>bla</i><sub>NDM-5</sub> was located on an IncFII plasmid of ... Read more >>

Antimicrob Agents Chemother (Antimicrobial agents and chemotherapy)
[2017, 61(7):]

Cited: 18 times

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Multidrug Resistant Pseudomonas aeruginosa Causing Prosthetic Valve Endocarditis: A Genetic-Based Chronicle of Evolving Antibiotic Resistance.

T Nicholas Domitrovic, Andrea M Hujer, Federico Perez, Steven H Marshall, Kristine M Hujer, Laila E Woc-Colburn, Mark Parta, Robert A Bonomo,

Background.  Successful treatment of infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa is thwarted by the emergence of antibiotic resistance and biofilm formation on prosthetic devices. Our aims were to decipher the molecular basis of resistance in a unique case of prosthetic valve endocarditis (PVE) caused by MDR P. aeruginosa. Methods. ... Read more >>

Open Forum Infect Dis (Open forum infectious diseases)
[2016, 3(4):ofw188]

Cited: 5 times

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