Characterization of a KPC-84 harboring Klebsiella pneumoniae ST11 clinical isolate with ceftazidime-avibactam resistance.

Publisher: Springer Country of Publication: Germany NLM ID: 8804297 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1435-4373 (Electronic) Linking ISSN: 09349723 NLM ISO Abbreviation: Eur J Clin Microbiol Infect Dis Subsets: MEDLINE

Publication: Berlin : Springer
Original Publication: [Wiesbaden, Federal Republic of Germany] : Vieweg, [c1988-

Klebsiella pneumoniae*/genetics ; Klebsiella pneumoniae*/drug effects ; Klebsiella pneumoniae*/enzymology ; Klebsiella pneumoniae*/isolation & purification ; Azabicyclo Compounds*/pharmacology ; Ceftazidime*/pharmacology ; Drug Combinations* ; beta-Lactamases*/genetics ; beta-Lactamases*/metabolism ; Microbial Sensitivity Tests* ; Klebsiella Infections*/microbiology ; Klebsiella Infections*/drug therapy ; Anti-Bacterial Agents*/pharmacology ; Bacterial Proteins*/genetics ; Bacterial Proteins*/metabolism; Humans ; Drug Resistance, Multiple, Bacterial/genetics ; China ; Amino Acid Substitution ; Escherichia coli/genetics ; Escherichia coli/drug effects

A novel KPC variant, KPC-84, identified in a Klebsiella pneumoniae isolate from China, exhibits a threonine (T) to proline (P) amino acid substitution at Ambler position 243(T243P), altering from the KPC-2 sequence. Cloning and expression of bla KPC-84 in Escherichia coli, with subsequent MIC assessments, revealed increased resistance to ceftazidime-avibactam and significantly reduced carbapenemase activity compared to KPC-2. Kinetic measurements showed that KPC-84 exhibited sligthly higher hydrolysis of ceftazidime and reduced affinity for avibactam compared to KPC-2. This study emphasizes the emerging diversity of KPC variants with ceftazidime-avibactam resistance, underscoring the complexity of addressing carbapenem-resistant Klebsiella pneumoniae infections.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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81861138055 National Natural Science Foundation of China; 312190022 West China Hospital of Sichuan University

Keywords: Klebsiella pneumoniae; Ceftazidime-avibactam; KPC

0 (Azabicyclo Compounds)
9M416Z9QNR (Ceftazidime)
0 (avibactam, ceftazidime drug combination)
0 (Drug Combinations)
EC 3.5.2.6 (beta-Lactamases)
0 (Anti-Bacterial Agents)
0 (Bacterial Proteins)
EC 3.5.2.6 (carbapenemase)

Date Created: 20240807 Date Completed: 20240916 Latest Revision: 20240925

20240925

10.1007/s10096-024-04910-y

39110337