Characterization of quinolone resistance mechanisms in Enterobacteriaceae isolated from companion animals in Europe (ComPath II study).

ComPath is an ongoing European programme dedicated to monitor antibiotic susceptibility of bacterial pathogens from diseased dogs and cats. The objective was to characterize determinants associated with quinolone resistance among 160 enrofloxacin non-wild type strains (100 Escherichia coli, 45 Proteus mirabilis, 14 Klebsiella pneumoniae, 1 Enterobacter cloacae) selected among 843 non-duplicate Enterobacteriaceae isolates collected in 12 European countries (2013-2014). These strains with non-wild type MICs of ≥0.25 mg/L, for P. mirabilis ≥0.5 mg/L, were screened for PMQR determinants (qnr, oqxAB, qepA and aac(6')-Ib-cr), and for QRDR mutations in gyrA, gyrB, parC and parE genes. Among them, 20% (32/160) carried at least one PMQR (18/32 qnrB, qnrS or qnrD, 10/32 aac(6')-Ib-cr and 13/32 oqxAB), and 80% (128/160) no PMQR. qnrB was detected in 3 E. coli, 2 K. pneumoniae and 1 E. cloacae strains; qnrS in 6 E. coli and 1 P. mirabilis and aac(6')-Ib-cr in 4 E. coli, 5 K. pneumoniae and 1 E. cloacae strains. All qnrD1 were detected in P. mirabilis. oqxAB was detected in 12/14 K. pneumoniae and 1 E. cloacae. No qepA genes were detected. From the 32 PMQR-positive strains, 10 showed enrofloxacin MICs ≤2 mg/L and 22 MICs ≥8 mg/L, the latter carrying 1-4 mutations in QRDR. For the 128 non-PMQR strains, 37 showed enrofloxacin MICs ≤2 mg/L with 0-2 QRDR mutations, and 91 MICs ≥4 mg/L carrying 1-4 QRDR mutations. In conclusion, qnr was the major PMQR and qnrD only detected in Proteeae. Mutations in QRDR play a markedly greater role in mediating fluoroquinolone resistance than PMQR.