Literature DB >> 28223379

Mutations in blaKPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases.

Ghady Haidar1, Cornelius J Clancy2,3,4, Ryan K Shields5,3, Binghua Hao3, Shaoji Cheng5, M Hong Nguyen1,5,3.   

Abstract

We identified four blaKPC-3 mutations in ceftazidime-avibactam-resistant clinical Klebsiella pneumoniae isolates, corresponding to D179Y, T243M, D179Y/T243M, and EL165-166 KPC-3 variants. Using site-directed mutagenesis and transforming vectors into Escherichia coli, we conclusively demonstrated that mutant blaKPC-3 encoded enzymes that functioned as extended-spectrum β-lactamases; mutations directly conferred higher MICs of ceftazidime-avibactam and decreased the MICs of carbapenems and other β-lactams. Impact was strongest for the D179Y mutant, highlighting the importance of the KPC Ω-loop.
Copyright © 2017 American Society for Microbiology.

Entities:  

Keywords:  KPC; ceftazidime-avibactam; drug resistance mechanisms; site-directed mutagenesis

Mesh：

Substances：

Year:  2017        PMID： 28223379      PMCID： PMC5404534          DOI： 10.1128/AAC.02534-16

Source DB:  PubMed          Journal:  Antimicrob Agents Chemother        ISSN： 0066-4804            Impact factor:   5.191


  23 in total

Review 1.  Defining an extended-spectrum beta-lactamase.

Authors:  D M Livermore
Journal:  Clin Microbiol Infect       Date:  2008-01       Impact factor: 8.067

2.  Redefining extended-spectrum beta-lactamases: balancing science and clinical need.

Authors:  Christian G Giske; Arnfinn S Sundsfjord; Gunnar Kahlmeter; Neil Woodford; Patrice Nordmann; David L Paterson; Rafael Cantón; Timothy R Walsh
Journal:  J Antimicrob Chemother       Date:  2008-10-28       Impact factor: 5.790

3.  Exploring the role of a conserved class A residue in the Ω-Loop of KPC-2 β-lactamase: a mechanism for ceftazidime hydrolysis.

Authors:  Peter S Levitt; Krisztina M Papp-Wallace; Magdalena A Taracila; Andrea M Hujer; Marisa L Winkler; Kerri M Smith; Yan Xu; Michael E Harris; Robert A Bonomo
Journal:  J Biol Chem       Date:  2012-07-26       Impact factor: 5.157

4.  Impact of the MIC of piperacillin-tazobactam on the outcome of patients with bacteremia due to extended-spectrum-β-lactamase-producing Escherichia coli.

Authors:  Pilar Retamar; Lorena López-Cerero; Miguel Angel Muniain; Álvaro Pascual; Jesús Rodríguez-Baño
Journal:  Antimicrob Agents Chemother       Date:  2013-04-22       Impact factor: 5.191

Review 5.  β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β-lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options?

Authors:  Patrick N A Harris; Paul A Tambyah; David L Paterson
Journal:  Lancet Infect Dis       Date:  2015-02-23       Impact factor: 25.071

Review 6.  Extended-spectrum beta-lactamases: a clinical update.

Authors:  David L Paterson; Robert A Bonomo
Journal:  Clin Microbiol Rev       Date:  2005-10       Impact factor: 26.132

7.  Activity of ceftazidime/avibactam against isogenic strains of Escherichia coli containing KPC and SHV β-lactamases with single amino acid substitutions in the Ω-loop.

Authors:  Marisa L Winkler; Krisztina M Papp-Wallace; Robert A Bonomo
Journal:  J Antimicrob Chemother       Date:  2015-05-08       Impact factor: 5.790

Review 8.  Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae: considerations for diagnosis, prevention and drug treatment.

Authors:  Mark E Rupp; Paul D Fey
Journal:  Drugs       Date:  2003       Impact factor: 9.546

9.  Association between the Presence of Aminoglycoside-Modifying Enzymes and In Vitro Activity of Gentamicin, Tobramycin, Amikacin, and Plazomicin against Klebsiella pneumoniae Carbapenemase- and Extended-Spectrum-β-Lactamase-Producing Enterobacter Species.

Authors:  Ghady Haidar; Ammar Alkroud; Shaoji Cheng; Travis M Churilla; Bryce M Churilla; Ryan K Shields; Yohei Doi; Cornelius J Clancy; M Hong Nguyen
Journal:  Antimicrob Agents Chemother       Date:  2016-08-22       Impact factor: 5.191

10.  Phenotypic and enzymatic comparative analysis of the novel KPC variant KPC-5 and its evolutionary variants, KPC-2 and KPC-4.

Authors:  Daniel J Wolter; Philip M Kurpiel; Neil Woodford; Marie-France I Palepou; Richard V Goering; Nancy D Hanson
Journal:  Antimicrob Agents Chemother       Date:  2008-11-17       Impact factor: 5.191
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  73 in total

1.  Identifying Spectra of Activity and Therapeutic Niches for Ceftazidime-Avibactam and Imipenem-Relebactam against Carbapenem-Resistant Enterobacteriaceae.

Authors:  Ghady Haidar; Cornelius J Clancy; Liang Chen; Palash Samanta; Ryan K Shields; Barry N Kreiswirth; M Hong Nguyen
Journal:  Antimicrob Agents Chemother       Date:  2017-08-24       Impact factor: 5.191

2.  Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-Resistant Klebsiella pneumoniae Bacteremia and Abscess in a Liver Transplant Recipient.

Authors:  Vasilios Athans; Elizabeth A Neuner; Habiba Hassouna; Sandra S Richter; George Keller; Mariana Castanheira; Kyle D Brizendine; Amy J Mathers
Journal:  Antimicrob Agents Chemother       Date:  2018-12-21       Impact factor: 5.191

3.  Exploring the Landscape of Diazabicyclooctane (DBO) Inhibition: Avibactam Inactivation of PER-2 β-Lactamase.

Authors:  Melina Ruggiero; Krisztina M Papp-Wallace; Magdalena A Taracila; Maria F Mojica; Christopher R Bethel; Susan D Rudin; Elise T Zeiser; Gabriel Gutkind; Robert A Bonomo; Pablo Power
Journal:  Antimicrob Agents Chemother       Date:  2017-05-24       Impact factor: 5.191

4.  KPC-53, a KPC-3 Variant of Clinical Origin Associated with Reduced Susceptibility to Ceftazidime-Avibactam.

Authors:  Vincenzo Di Pilato; Noemi Aiezza; Valentina Viaggi; Alberto Antonelli; Luigi Principe; Tommaso Giani; Francesco Luzzaro; Gian Maria Rossolini
Journal:  Antimicrob Agents Chemother       Date:  2020-12-16       Impact factor: 5.191

5.  Evaluation of the Synergy of Ceftazidime-Avibactam in Combination with Meropenem, Amikacin, Aztreonam, Colistin, or Fosfomycin against Well-Characterized Multidrug-Resistant Klebsiella pneumoniae and Pseudomonas aeruginosa.

Authors:  Sandra Mikhail; Nivedita B Singh; Razieh Kebriaei; Seth A Rice; Kyle C Stamper; Mariana Castanheira; Michael J Rybak
Journal:  Antimicrob Agents Chemother       Date:  2019-07-25       Impact factor: 5.191

6.  Ceftazidime-Avibactam Resistance Associated with Increased bla KPC-3 Gene Copy Number Mediated by pKpQIL Plasmid Derivatives in Sequence Type 258 Klebsiella pneumoniae.

Authors:  Marco Coppi; Vincenzo Di Pilato; Francesco Monaco; Tommaso Giani; Pier Giulio Conaldi; Gian Maria Rossolini
Journal:  Antimicrob Agents Chemother       Date:  2020-03-24       Impact factor: 5.191

Review 7.  Recognizing and Overcoming Resistance to New Beta-Lactam/Beta-Lactamase Inhibitor Combinations.

Authors:  Stephanie Ho; Lynn Nguyen; Trang Trinh; Conan MacDougall
Journal:  Curr Infect Dis Rep       Date:  2019-09-09       Impact factor: 3.725

Review 8.  Epidemiology of β-Lactamase-Producing Pathogens.

Authors:  Karen Bush; Patricia A Bradford
Journal:  Clin Microbiol Rev       Date:  2020-02-26       Impact factor: 26.132

9.  Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime-Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

Authors:  Ryan K Shields; M Hong Nguyen; Liang Chen; Ellen G Press; Barry N Kreiswirth; Cornelius J Clancy
Journal:  Antimicrob Agents Chemother       Date:  2018-04-26       Impact factor: 5.191

10.  Verification of Ceftazidime-Avibactam and Ceftolozane-Tazobactam Susceptibility Testing Methods against Carbapenem-Resistant Enterobacteriaceae and Pseudomonas aeruginosa.

Authors:  Ryan K Shields; Cornelius J Clancy; A William Pasculle; Ellen G Press; Ghady Haidar; Binghua Hao; Liang Chen; Barry N Kreiswirth; M Hong Nguyen
Journal:  J Clin Microbiol       Date:  2018-01-24       Impact factor: 5.948
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