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Mutations in blaKPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases.
Antimicrob Agents Chemother. 2017 05; 61(5)AA

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.

Authors+Show Affiliations

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.University of Pittsburgh, Pittsburgh, Pennsylvania, USA cjc76@pitt.edu. XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.University of Pittsburgh, Pittsburgh, Pennsylvania, USA. XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.University of Pittsburgh, Pittsburgh, Pennsylvania, USA.University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. University of Pittsburgh, Pittsburgh, Pennsylvania, USA. XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28223379

Citation

Haidar, Ghady, et al. "Mutations in blaKPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum Β-Lactamases." Antimicrobial Agents and Chemotherapy, vol. 61, no. 5, 2017.
Haidar G, Clancy CJ, Shields RK, et al. Mutations in blaKPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases. Antimicrob Agents Chemother. 2017;61(5).
Haidar, G., Clancy, C. J., Shields, R. K., Hao, B., Cheng, S., & Nguyen, M. H. (2017). Mutations in blaKPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases. Antimicrobial Agents and Chemotherapy, 61(5). https://doi.org/10.1128/AAC.02534-16
Haidar G, et al. Mutations in blaKPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum Β-Lactamases. Antimicrob Agents Chemother. 2017;61(5) PubMed PMID: 28223379.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutations in blaKPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases. AU - Haidar,Ghady, AU - Clancy,Cornelius J, AU - Shields,Ryan K, AU - Hao,Binghua, AU - Cheng,Shaoji, AU - Nguyen,M Hong, Y1 - 2017/04/24/ PY - 2016/11/28/received PY - 2017/02/07/accepted PY - 2017/2/23/pubmed PY - 2018/1/13/medline PY - 2017/2/23/entrez KW - KPC KW - ceftazidime-avibactam KW - drug resistance mechanisms KW - site-directed mutagenesis JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 61 IS - 5 N2 - 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. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/28223379/Mutations_in_blaKPC_3_That_Confer_Ceftazidime_Avibactam_Resistance_Encode_Novel_KPC_3_Variants_That_Function_as_Extended_Spectrum_β_Lactamases_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=28223379 DB - PRIME DP - Unbound Medicine ER -