Increase in antimicrobial resistance and emergence of major international high-risk clonal lineages in dogs and cats with urinary tract infection: 16 year retrospective study Ca ´ tia Marques 1 , Adriana Belas 1 , Andreia Franco 1 , Catarina Aboim 1 , Luı ´s Telo Gama 2 and Constanc¸a Pomba 1 * 1 Laboratory of Resistance to Antibiotics and Biocides, CIISA, Faculdade de Medicina Veterina ´ ria, Universidade de Lisboa (FMV-UL), Lisbon, Portugal; 2 Animal Genetic Resources, CIISA, Faculdade de Medicina Veterina ´ ria, Universidade de Lisboa (FMV-UL), Lisbon, Portugal *Corresponding author. Tel: !351-21-365-2837; Fax: !351-21-365-2897; E-mail: cpomba@fmv.ulisboa.pt Received 11 June 2017; returned 1 August 2017; revised 22 September 2017; accepted 4 October 2017 Objectives: To evaluate temporal trends in antimicrobial resistance, over 16 years, in bacteria isolated from dogs and cats with urinary tract infection (UTI) and the clonal lineages of bacteria harbouring critical antimicrobial re- sistance mechanisms. Methods: Antimicrobial susceptibility testing was conducted for 948 bacteria isolated from dogs and cats with UTI (1999–2014). Resistance mechanisms were detected by PCR, namely ESBL/AmpC in third-generation ceph- alosporin (3GC)-resistant Escherichia coli and Proteus mirabilis, mecA in methicillin-resistant staphylococci, and aac(6 0 )-Ieaph(2 00 )-Ia and aph(2 00 )-1d in high-level gentamicin-resistant (HLGR) enterococci. Resistant bacteria were typed by MLST, and temporal trends in E. coli and Enterobacteriaceae antimicrobial resistance were deter- mined by logistic regression. Results: Enterobacteriaceae had a significant temporal increase in resistance to amoxicillin/clavulanate, 3GCs, trimethoprim/sulfamethoxazole, fluoroquinolones, gentamicin and tetracycline (P , 0.001). An increase in MDR was also detected (P , 0.0001). 3GC resistance was mainly caused by the presence of bla CTX-M-15 and bla CMY-2 in E. coli and the presence of bla CMY-2 in P. mirabilis. Two major 3GC-resistant E. coli clonal lineages were detected: O25b:H4-B2-ST131 and ST648. The mecA gene was detected in 9.2% (n " 11/119) of Staphylococcus spp., including MRSA clonal complex (CC) 5 (n " 2) and methicillin-resistant Staphylococcus epidermidis CC5 (n " 4). A temporal increase in MDR methicillin-resistant Staphylococcus pseudintermedius was detected (P " 0.0069). Some ampicillin-resistant and/or HLGR Enterococcus spp. were found to belong to hospital-adapted CCs, namely Enterococcus faecalis ST6-CC6 (n " 1) and Enterococcus faecium CC17 (n " 8). Conclusions: The temporal increase in antimicrobial resistance and in MDR bacteria causing UTI in dogs and cats creates important therapeutic limitations in veterinary medicine. Furthermore, the detection of MDR high-risk clonal lineages raises public health concerns since companion animals with UTI may contribute to the spread of such bacteria. Introduction Urinary tract infections (UTIs) are frequently diagnosed in veterin- ary medicine 1 and may require antimicrobial treatment. 2 Since antimicrobial resistance is known to change geographically and over time, 3 updated and long-term studies are critical to investi- gate the spread of antimicrobial resistance. Escherichia coli and Proteus mirabilis are the most frequently isolated Gram-negative bacteria from dogs and cats with UTI, while Staphylococcus spp. and Enterococcus spp. are the most common Gram-positive bac- teria. 1,4 These bacteria, isolated from dogs and cats, may harbour clinically and epidemiologically important resistance mechanisms of human and veterinary relevance such as ESBL, 5,6 cephalospori- nases (AmpC), 7 PBP2a 8 and high-level gentamicin resistance (HLGR) bifunctional enzyme. 9 Moreover, the detection of MDR bac- teria in dogs and cats is being increasingly reported, 7,8 posing a dif- ficult veterinary therapeutic challenge and often requiring the use of antimicrobials critically important to humans. 10 With the grow- ing contact between companion animals and humans, the risk of animal-to-human transfer of such bacteria is of concern. 11 Additionally, several studies have shown that dogs and cats may share uropathogenic bacteria with the remaining household members. 12 Therefore, the identification of the clonal lineages of V C The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com. 377 J Antimicrob Chemother 2018; 73: 377–384 doi:10.1093/jac/dkx401 Advance Access publication 9 November 2017 Downloaded from https://academic.oup.com/jac/article-abstract/73/2/377/4609341 by guest on 30 May 2020