Fluoroquinolone resistance is being increasingly identified in both human and veterinary practice. In this study, a total of 41 multidrug-resistant (MDR) Escherichia coli isolates from canine extraintestinal infections were examined to compare fluoroquinolone minimum inhibitory concentrations (MICs) for enrofloxacin, marbofloxacin, and pradofloxacin. In addition, plasmid-mediated quinolone resistance (PMQR) mechanisms were investigated and chromosomal fluoroquinolone resistance mechanisms were examined and characterized. Isolates represented 3 clonal groups (CGs) cultured from canine extraintestinal infections (61% involved the urinary tract), and were obtained from 22 dogs from 1999 to 2004. Isolates from each CG had the PMQR genes qnrA1, qnrB2, qnrS1, and qepA, and all isolates in the study were resistant to fluoroquinolones. Qnr genes were identified in 83% of isolates (n = 34) and multiple Qnr genes were identified in 59% (n = 24). Chromosomal resistance mechanisms were characterized for fluoroquinolones in 13 representative isolates. Three mutations in the quinolone resistance determining region (QRDR) were identified in CG1 isolates. An additional parC mutation was identified in CG2 and CG3 isolates; this was seen in higher fluoroquinolone MICs than in CG1. Organic solvent tolerance was detected in 61.5% of isolates, and enhanced efflux was noted in all 13 isolates based on a 4-fold or greater decrease in enrofloxacin MIC when incubated with an efflux pump inhibitor. An acrR mutation (with the potential to cause acrAB multidrug efflux pump overexpression) was identified in CG1 strains. In sum, these findings collectively suggested that fluoroquinolone resistance in this population of MDR E coli isolates was due to chromosomal target mutations in QRDR, enhanced efflux, and transferable PMQR mechanisms. Study supported by Bayer Healthcare

Commentary: This report provides additional evidence supporting judicious antibiotic use by medical professionals through the identification of diverse resistance mechanisms of E coli isolates to fluoroquinolones. Fluoroquinolones are powerful players in our therapeutic arsenal, and future elucidation of resistance mechanisms and phenotypes will allow prevention of increased clinical resistance in current and future drug classes. Isolates in this study were drawn from canine extraintestinal infections and can serve as a source pool for fluoroquinolone-resistant organisms in clinical patients.—Indu Mani, DVM, DSc

Fluoroquinolone resistance mechanisms in multidrug-resistant Escherichia coli isolated from extraintestinal infections in dogs. Gibson JS, Cobbold RN, Kyaw-Tanner MT, et al. VET MICROBIOL 146:161-166, 2010.