The objective of the study was to assess the prevalence of plasmid-mediated quinolone resistance (PMQR) genes (qnrA, qnrB, qnrC, qnrD, qnrS, aac(6')-Ib-cr, qepA, and oqxAB) in a collection of 120 extended-spectrum β-lactamases (ESBLs)-producing enterobacteria and to characterize them. Overall, PMQR determinants were detected in 72 (60%) isolates (20 Escherichia coli, 32 Klebsiella pneumoniae, and 20 Enterobacter cloacae). PMQR frequencies were as follows: qnr genes (25.8%), oqxAB (21.6%), and aac(6')-Ib-cr variant (19.2%). Four qnr alleles were identified as qnrB1 (83.8%), qnrB4 (6.4%), qnrB2 (3.2%), and qnrS1 (6.4%). qnr genes were mainly detected in E. cloacae (50%), aac(6')-Ib-cr in E. coli (47.5%), and oqxAB in K. pneumoniae (65%). Overall, blaCTX-M-15 (90.3%) was the most prevalent blaESBL type followed by blaSHV-12 (6.4%) and blaSHV-27 (2.7%). Rates of mutations in gyrA and parC genes were 75% for E. coli, 72.8% for K. pneumoniae, and 50% for E. cloacae. Isolates with mutations in their quinolone resistance-determining regions exhibited high fluoroquinolones resistance levels compared to those with wild ones. Genetic study of PMQR-harboring isolates revealed a great genomic diversity among each Enterobacteriaceae species. Our findings indicate the high prevalence of PMQR determinants among ESBL-producing Enterobacteriaceae isolates from our hospital and their diffusion in various unrelated CTX-M-15-producing clones.