ORIGINAL ARTICLE Dissemination of plasmid-mediated fosfomycin resistance fosA3 among multidrug-resistant Escherichia coli from livestock and other animals P.L. Ho 1,2 , J. Chan 1 , W.U. Lo 1 , P.Y. Law 1 , Z. Li 1 , E.L. Lai 1 and K.H. Chow 1 1 Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong, China 2 Carol Yu Center for Infection, University of Hong Kong, Pokfulam, Hong Kong, China Keywords antimicrobial drug resistance, CTX-M beta-lactamase, Enterobacteriaceae, fosfomycin resistance, plasmids. Correspondence Pak-Leung Ho, Division of Infectious Diseases, Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong SAR, China. E-mail: plho@hkucc.hku.hk 2013/1565: received 3 September 2012, revised 29 November 2012 and accepted 4 December 2012 doi:10.1111/jam.12099 Abstract Aims: To investigate plasmid-mediated fosfomycin resistance related to fosA3 in Escherichia coli isolates collected from different animals in Hong Kong, China, 2008–2010. Methods and Results: In total, 2106 faecal specimens from 210 cattle, 214 pigs, 460 chickens, 398 stray cats, 368 stray dogs and 456 wild rodents were cultured. The faecal colonization rates of fosfomycin-resistant E. coli were as follows: 112% in pigs, 86% in cattle, 73% in chickens, 24% in dogs, 08% in cats and 15% in rodents. The cultures yielded 1693 isolates of which 831 were extended-spectrum b-lactamases (ESBL) producers. Fosfomycin-resistant isolates were more likely than fosfomycin-susceptible isolates to be producers of ESBL and to have resistance to chloramphenicol, ciprofloxacin, cotrimoxazole, gentamicin and tetracycline. Of the 101 fosfomycin-resistant isolates, 97 (960%) isolates were fosA3 positive and 94 (931%) were bla CTX-M positive. PCR mapping showed that the fosA3-containing regions were flanked by IS26, both upstream and downstream in 81 (835%) isolates, and by an upstream bla CTX-M-14 -containing transposon-like structure (DISEcp1-bla CTX-M- 14 -DIS903 or ISEcp1-IS10 -bla CTX-M-14 -DIS903) and a downstream IS26 in 14 (144%) isolates. For the remaining two isolates, fosA3 was flanked by a downstream IS26 but the upstream part cannot be defined. In a random subset of 18 isolates, fosA3 was carried on transferable plasmids with sizes of 50–200 kb and the following replicons: F2:A-B- (n = 3), F16:A1:B- (n = 2), F24:A-B- (n = 1), N (n = 1), B/O (n = 1) and untypeable (n = 3). Significance and Impact of the Study: This study demonstrates the emergence of fosA3-mediated fosfomycin resistance among multidrug-resistant E. coli isolates from various animals. IS26 transposon-like structures might be the main vehicles for dissemination of fosA3. Introduction The spread of extended-spectrum b-lactamases (ESBLs) and carbapenemases in Enterobacteriaceae has renewed interest to revisit the clinical use of old antibiotics such as fosfomycin for treating infections (Falagas et al. 2010; Gutierrez et al. 2010; Soraci et al. 2011). In Escherichia coli, resistance to fosfomycin is uncommon and is mainly caused by chromosomal factors (Takahata et al. 2010). However, two novel plasmid-mediated fosfomycin enzymes, FosA3 and FosC2 have been found among CTX-M-producing E. coli in Japan (Wachino et al. 2010). Furthermore, a recent study involving strains from pets in China demonstrated that 29 of 33 fosfomycin-resistant E. coli were positive for the plasmid-mediated fosA3 gene and all of them were CTX-M producers (Hou et al. 2012). It is often held that exposure to antibiotics is a major factor in maintaining antimicrobial resistance. Nonetheless, high prevalence of certain antibiotic-resis- tant genes has been detected in bacteria originating from Journal of Applied Microbiology 114, 695--702 © 2012 The Society for Applied Microbiology 695 Journal of Applied Microbiology ISSN 1364-5072