In 1998, the first plasmid-mediated gene involved in quinolone resistance (currently named qnrA1) was reported. Extra qnr-like plasmid-mediated genes (qnrB, qnrS, qnrC, qnrD) and their chromosomal homologues have also been characterized. These genes code for a pentapeptide repeat protein that protects type II topoisomerases from quinolones. Since then, there have been reports of two other plasmid-mediated resistance mechanisms: the modification of quinolones with a piperazinyl substituent by the acetyltransferase, Aac(6')-Ib-cr; and active efflux by QepA and OqxAB, pumps related to major facilitator superfamily (MFS) transporters. These genes have a wide geographic distribution (mainly in Enterobacteriaceae). Because of the difficulties of phenotypic detection of this type of resistance, its real prevalence is only partially known. One important point is that although these mechanisms cause only low-level resistance, they favor and complement the selection of other resistance mechanisms.