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. 2020 Jul 22;64(8):e00321-20.
doi: 10.1128/AAC.00321-20. Print 2020 Jul 22.

KPC-50 Confers Resistance to Ceftazidime-Avibactam Associated with Reduced Carbapenemase Activity

Laurent Poirel  1   2   3 , Xavier Vuillemin  4 , Mario Juhas  4 , Amandine Masseron  4 , Ursina Bechtel-Grosch  5 , Simon Tiziani  6 , Stefano Mancini  7 , Patrice Nordmann  4   2   3   8
Affiliations

KPC-50 Confers Resistance to Ceftazidime-Avibactam Associated with Reduced Carbapenemase Activity

Laurent Poirel et al. Antimicrob Agents Chemother. .

Abstract

KPC-50 is a KPC-3 variant identified from a Klebsiella pneumoniae clinical isolate recovered in Switzerland in 2019. Compared to KPC-3, KPC-50 shows (i) a three-amino-acid insertion (Glu-Ala-Val) between amino acids 276 and 277, (ii) an increased affinity to ceftazidime, (iii) a decreased sensitivity to avibactam, explaining the ceftazidime-avibactam resistance, and (iv) an association with a sharp reduction of its carbapenemase activity.

Keywords: KPC; Klebsiella pneumoniae; ceftazidime-avibactam.

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Figures

FIG 1
FIG 1
Analysis of ceftazidime hydrolysis. (A) KPC-50 and KPC-3 (1 μM enzyme) hydrolysis of 25 μM ceftazidime (CAZ) at room temperature. (B and C) Competitive inhibition curves determined with 50 μM nitrocefin and increasing concentrations of CAZ with 0.1 μM KPC-50 (B) and 0.1 μM KPC-3 (C) at room temperature. Nitrocefin absorbance was measured.
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