Antimicrobial susceptibility and mechanisms of fosfomycin resistance in extended-spectrum beta-lactamase-producing Escherichia coli strains from urinary tract infections inWenzhou, China

作者：Bi, Wenzi; Li, Bin; Song, Jiangning; Hong, Youliang; Zhang, Xiaoxiao; Liu, Haiyang; Lu, Hong; Zhou, Tieli^*; Cao, Jianming^*

来源：International Journal of Antimicrobial Agents, 2017, 50(1): 29-34.

DOI：10.1016/j.ijantimicag.2017.02.010

• Escherichia coli
• Extended-spectrum beta-lactamase
• Fosfomycin
• fosA3

Fosfomycin in combination with various antibiotics represents an excellent clinically efficacious regimen for the treatment of urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)producing Escherichia coli. Underlying mechanisms of fosfomycin resistance remain largely uncharacterised. To investigate the antibacterial efficacy of fosfomycin against ESBL-producing E. coli, 356 non-repetitive ESBL-producing E. coli clinical isolates were collected from urine specimens from patients with UTI in Wenzhou, China, from January 2011 to December 2015. Antimicrobial sensitivity testing indicated that 6.7% (24/356) of the ESBL-producing E. coli strains were resistant to fosfomycin. The fosA3 gene encoding a fosfomycin-modifying enzyme was detected in 20 isolates by PCR and sequencing, alone or in combination with other ESBL determinants. Conjugation experiments and Southern blotting demonstrated that 70% (14/20) of the fosA3-positive isolates possessed transferable plasmids (ca. 54.2 kb) coharbouring the ESBL resistance gene blaCTX-M and the fosfomycin resistance gene fosA3. Among the four fosfomycin-resistant fosA3-negative E. coli isolates, three contained amino acid substitutions (Ile28Asn and Phe30Leu in MurA and Leu297Phe in GlpT). The results indicate that presence of the fosA3 gene is the primary mechanism of fosfomycin resistance in ESBL-producing E. coli isolates in Wenzhou, China. In addition, a plasmid (ca. 54.2 kb) co-harbouring fosA3 and blaCTX-M genes is horizontally transferable. Furthermore, a low degree of homology in the fosfomycin-resistant E. coli was confirmed using multilocus sequence typing (MLST), suggesting that there is no obvious phenomenon of clonal dissemination.

• 出版日期2017-7
• 单位温州医科大学