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Emergence of ceftazidime/avibactam resistance in carbapenem-resistant Klebsiella pneumoniae in China

Zhang, P. ; Shi, Q. ; Hu, H. ; Hong, B. ; Wu, X. ; Du, X. ; Akova, M. ; Yu, Y.

Clinical microbiology and infection, 2020-01, Vol.26 (1), p.124.e1-124.e4 [Periódico revisado por pares]

England: Elsevier Ltd

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  • Título:
    Emergence of ceftazidime/avibactam resistance in carbapenem-resistant Klebsiella pneumoniae in China
  • Autor: Zhang, P. ; Shi, Q. ; Hu, H. ; Hong, B. ; Wu, X. ; Du, X. ; Akova, M. ; Yu, Y.
  • Assuntos: blaKPC ; Carbapenem-resistant Klebsiella pneumoniae ; Ceftazidime/avibactam ; Metallo-β-lactamase ; Ω-loop
  • É parte de: Clinical microbiology and infection, 2020-01, Vol.26 (1), p.124.e1-124.e4
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: The aim was to investigate the activity of ceftazidime/avibactam (CAZ/AVI) against carbapenem-resistant Klebsiella pneumoniae (CRKP) and identify the resistance mechanisms before CAZ/AVI coming to Chinese market. Clinical CRKP isolates were continuously collected from 36 tertiary hospitals in China from 1 March 2017 to 31 July 2017. CAZ/AVI MICs were determined by agar dilution method. CAZ/AVI resistant isolates were submitted to whole genome sequencing. The copy number and relative expression of blaKPC were determined by quantitative PCR. A total of 872 CRKP isolates were collected, and MIC50 and MIC90 of CAZ/AVI were 4 and 8 mg/L. The resistant rate of CAZ/AVI was 3.7% (32/872). Among the resistant isolates, 53.1% (17/32) were metallo-β-lactamase-producing K. pneumoniae (MBL-KP), 40.6% (13/32) were Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) and 6.3% (2/32) produced both MBL and KPC. One of the KPC-KP with high level CAZ/AVI resistance (>128 mg/L) harboured mutated blaKPC-2 (D179Y). In 12 wild-type blaKPC-2 isolates, the relative copy number and expression of blaKPC-2 gene were 2.5-fold and 2.7-fold higher than that in the CAZ/AVI MIC ≤0.5 mg/L group (p < 0.05), and when added avibactam at a fixed concentration of 8 mg/L, 91.7% (11/12) isolates could restore susceptibility. Resistance against CAZ/AVI in CRKP emerged before clinical use of CAZ/AVI in China, although most of the CRKP isolates maintained the susceptibility. MBL production, blaKPC-2 point mutation and high KPC expression played an important role in CAZ/AVI resistance.
  • Editor: England: Elsevier Ltd
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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