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J Microbiol Immunol Infect. 2017 Oct;50(5):653-661. doi: 10.1016/j.jmii.2017.03.003. Epub 2017 Jun 28.

The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan.

Author information

1
Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan.
2
Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
3
National Institutes of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
4
Department of Internal Medicine and Medical Research, Chi Mei Medical Center, Tainan, Taiwan; Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.
5
Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
6
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
7
Department of Clinical Pathology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
8
Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
9
Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: d830166@gmail.com.

Abstract

BACKGROUND:

Epidemiology of fosfomycin susceptibility and the plasmid-mediated fosfomycinase genes of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in Taiwan remain unclear.

METHODS:

642 CRKP clinical isolates were collected from a nation-wide surveillance study (16 hospitals) in Taiwan in 2012-2013. Antimicrobial susceptibilities were determined. PFGE and MLST determined the clonal relatedness. Carbapenemases and fosfomycinases genes were detected by PCR, and their flanking regions were determined by PCR and sequencing. Synergistic activity of meropenem with fosfomycin was examined by the checkerboard method.

RESULTS:

In total, 36.4% (234/642) of CRKP isolates in Taiwan were resistant to fosfomycin. Among 234 fosfomycin-resistant CRKP isolates, PFGE analysis revealed 81 pulsotypes. Pulsotype XXIII (n = 63) was predominant and belonged to ST11. 71 had carbapnemases (65 blaKPC-2-positive, 1 blaVIM-1-positive and 5 blaIMP-8-positive) and 62 had fosfomycinases (35 fosA3-positive and 27 foskp96-positive). Only 18.5% (5/27) of foskp96-positive isolates carried foskp96 and blaKPC-2, while 71.4% (25/35) of fosA3-positive isolates contained fosA3 and blaKPC-2. There were five types of flanking sequences for fosA3, and 85.7% (30/35) of fosA3 genes were flanked by IS26, suggesting possible horizontal gene transfer. Synergistic effect of fosfomycin and meropenem was observed in all 25 randomly selected pulsotype XXIII strains (100%; 25/25), even those containing fosfomycinase (48%, 12/25) or carbapnemase (96%, 24/25).

CONCLUSIONS:

A clone (pulsotype XXIII, ST11) has been found to be prevailing among fosfomycin-resistant CRKP in Taiwan. According to the in vitro data, the combination of fosfomycin and meropenem is a potentially alternative choice.

KEYWORDS:

Carbapenem resistance; Fosfomycin; bla(KPC-2); fosA3; foskp96

PMID:
28705769
DOI:
10.1016/j.jmii.2017.03.003
[Indexed for MEDLINE]
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