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

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...

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Main Authors: Sung-Pin Tseng, Sheng-Fan Wang, Ling Ma, Ting-Yin Wang, Tsung-Ying Yang, L. Kristopher Siu, Yin-Ching Chuang, Pei-Shan Lee, Jann-Tay Wang, Tsu-Lan Wu, Jung-Chung Lin, Po-Liang Lu
Format: Article
Language:English
Published: Elsevier 2017-10-01
Series:Journal of Microbiology, Immunology and Infection
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1684118217300920
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author Sung-Pin Tseng
Sheng-Fan Wang
Ling Ma
Ting-Yin Wang
Tsung-Ying Yang
L. Kristopher Siu
Yin-Ching Chuang
Pei-Shan Lee
Jann-Tay Wang
Tsu-Lan Wu
Jung-Chung Lin
Po-Liang Lu
author_facet Sung-Pin Tseng
Sheng-Fan Wang
Ling Ma
Ting-Yin Wang
Tsung-Ying Yang
L. Kristopher Siu
Yin-Ching Chuang
Pei-Shan Lee
Jann-Tay Wang
Tsu-Lan Wu
Jung-Chung Lin
Po-Liang Lu
author_sort Sung-Pin Tseng
collection DOAJ
description 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.
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spelling doaj.art-f86a2e1d49fe4214825e91be174fc7452022-12-21T17:33:17ZengElsevierJournal of Microbiology, Immunology and Infection1684-11822017-10-0150565366110.1016/j.jmii.2017.03.003The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in TaiwanSung-Pin Tseng0Sheng-Fan Wang1Ling Ma2Ting-Yin Wang3Tsung-Ying Yang4L. Kristopher Siu5Yin-Ching Chuang6Pei-Shan Lee7Jann-Tay Wang8Tsu-Lan Wu9Jung-Chung Lin10Po-Liang Lu11Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, TaiwanNational Institutes of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanDepartment of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, TaiwanNational Institutes of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanDepartment of Internal Medicine and Medical Research, Chi Mei Medical Center, Tainan, TaiwanDepartment of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanDepartment of Clinical Pathology, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanDivision of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDepartment of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanBackground: 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.http://www.sciencedirect.com/science/article/pii/S1684118217300920FosfomycinCarbapenem resistancefosA3foskp96blaKPC-2
spellingShingle Sung-Pin Tseng
Sheng-Fan Wang
Ling Ma
Ting-Yin Wang
Tsung-Ying Yang
L. Kristopher Siu
Yin-Ching Chuang
Pei-Shan Lee
Jann-Tay Wang
Tsu-Lan Wu
Jung-Chung Lin
Po-Liang Lu
The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan
Journal of Microbiology, Immunology and Infection
Fosfomycin
Carbapenem resistance
fosA3
foskp96
blaKPC-2
title The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan
title_full The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan
title_fullStr The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan
title_full_unstemmed The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan
title_short The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan
title_sort plasmid mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem resistant klebsiella pneumoniae isolates in taiwan
topic Fosfomycin
Carbapenem resistance
fosA3
foskp96
blaKPC-2
url http://www.sciencedirect.com/science/article/pii/S1684118217300920
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