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      In Vivo Emergence of Resistance to Novel Cephalosporin–β-Lactamase Inhibitor Combinations through the Duplication of Amino Acid D149 from OXA-2 β-Lactamase (OXA-539) in Sequence Type 235 Pseudomonas aeruginosa

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          ABSTRACT

          Resistance development to novel cephalosporin–β-lactamase inhibitor combinations during ceftazidime treatment of a surgical infection by Pseudomonas aeruginosa was investigated. Both initial (97C2) and final (98G1) isolates belonged to the high-risk clone sequence type (ST) 235 and were resistant to carbapenems ( oprD), fluoroquinolones (GyrA-T83I, ParC-S87L), and aminoglycosides ( aacA7/aacA8/aadA6). 98G1 also showed resistance to ceftazidime, ceftazidime-avibactam, and ceftolozane-tazobactam. Sequencing identified bla OXA-2 in 97C2, but 98G1 contained a 3-bp insertion leading to the duplication of the key residue D149 (designated OXA-539). Evaluation of PAO1 transformants producing cloned OXA-2 or OXA-539 confirmed that D149 duplication was the cause of resistance. Active surveillance of the emergence of resistance to these new valuable agents is warranted.

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          Author and article information

          Journal
          Antimicrob Agents Chemother
          Antimicrob. Agents Chemother
          aac
          aac
          AAC
          Antimicrobial Agents and Chemotherapy
          American Society for Microbiology (1752 N St., N.W., Washington, DC )
          0066-4804
          1098-6596
          3 July 2017
          24 August 2017
          September 2017
          : 61
          : 9
          : e01117-17
          Affiliations
          Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa), Palma de Mallorca, Spain
          Author notes
          Address correspondence to Antonio Oliver, antonio.oliver@ 123456ssib.es .

          Citation Fraile-Ribot PA, Mulet X, Cabot G, del Barrio-Tofiño E, Juan C, Pérez JL, Oliver A. 2017. In vivo emergence of resistance to novel cephalosporin–β-lactamase inhibitor combinations through the duplication of amino acid D149 from OXA-2 β-lactamase (OXA-539) in sequence type 235 Pseudomonas aeruginosa. Antimicrob Agents Chemother 61:e01117-17. https://doi.org/10.1128/AAC.01117-17.

          Author information
          http://orcid.org/0000-0002-6452-9945
          http://orcid.org/0000-0001-9327-1894
          Article
          PMC5571340 PMC5571340 5571340 01117-17
          10.1128/AAC.01117-17
          5571340
          28674059
          d1f948e0-fcdf-431a-9f66-9881a301d8c3
          Copyright © 2017 American Society for Microbiology.

          All Rights Reserved.

          History
          : 29 May 2017
          : 27 June 2017
          : 29 June 2017
          Page count
          Figures: 1, Tables: 2, Equations: 0, References: 31, Pages: 5, Words: 2924
          Funding
          Funded by: Ministerio de Economía y Competitividad of Spain, Instituto de Salud Carlos III
          Award ID: RD12/0015/0006
          Award ID: RD15/00160004
          Award ID: PI15/00088
          Award Recipient : Antonio Oliver
          Categories
          Mechanisms of Resistance
          Custom metadata
          September 2017

          extended-spectrum OXA, Pseudomonas aeruginosa ,multidrug resistance,ceftolozane-tazobactam,ceftazidime-avibactam

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