Xiucai Zhang1, Wenzi Bi2, Lijiang Chen1, Yizhi Zhang1, Renchi Fang1, Jianming Cao3, Tieli Zhou4. 1. Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. 2. Department of Clinical Laboratory, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang Province, China. 3. School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: wzcjming@163.com. 4. Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: wyztli@163.com.
Abstract
OBJECTIVES: The aim of this study was to investigate the mechanisms of fosfomycin resistance and epidemiological characteristics in fosfomycin-resistant enterococci in China. METHODS: A collection of 761 enterococcal clinical isolates from a teaching hospital in Wenzhou, China were studied. The fosfomycin susceptibility of the isolates was investigated by the agar dilution method. The isolates were also analysed for mechanisms of re fosfomycin resistance by PCR and quantitative real-time PCR. Furthermore, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed to analyse the molecular epidemiological characteristics of the fosfomycin-resistant isolates. RESULTS: In this study, 0.3% (1/372) of Enterococcus faecalis and 4.9% (19/389) of Enterococcus faecium clinical isolates were found to be resistant to fosfomycin. Among the 20 fosfomycin-resistant isolates, 5 harboured the fosB gene, 10 carried multiple amino acid substitutions in MurA, and 6 showed high-level expression of the fosX gene; of note, 1 isolate simultaneously carried fosB and amino acid mutation in MurA. Furthermore, a high degree of homology in the fosfomycin-resistant enterococci was confirmed using MLST and PFGE. CONCLUSION: These finding demonstrate that the fosB gene, mutations in the fosfomycin target enzyme MurA, and a high expression level of fosX were the resistance mechanisms in these fosfomycin-resistant enterococci.
OBJECTIVES: The aim of this study was to investigate the mechanisms of fosfomycin resistance and epidemiological characteristics in fosfomycin-resistant enterococci in China. METHODS: A collection of 761 enterococcal clinical isolates from a teaching hospital in Wenzhou, China were studied. The fosfomycin susceptibility of the isolates was investigated by the agar dilution method. The isolates were also analysed for mechanisms of re fosfomycin resistance by PCR and quantitative real-time PCR. Furthermore, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed to analyse the molecular epidemiological characteristics of the fosfomycin-resistant isolates. RESULTS: In this study, 0.3% (1/372) of Enterococcus faecalis and 4.9% (19/389) of Enterococcus faecium clinical isolates were found to be resistant to fosfomycin. Among the 20 fosfomycin-resistant isolates, 5 harboured the fosB gene, 10 carried multiple amino acid substitutions in MurA, and 6 showed high-level expression of the fosX gene; of note, 1 isolate simultaneously carried fosB and amino acid mutation in MurA. Furthermore, a high degree of homology in the fosfomycin-resistant enterococci was confirmed using MLST and PFGE. CONCLUSION: These finding demonstrate that the fosB gene, mutations in the fosfomycin target enzyme MurA, and a high expression level of fosX were the resistance mechanisms in these fosfomycin-resistant enterococci.