ABSTRACT We studied a collection of 105 clinical enterobacteria with unusual phenotypes of quinolone susceptibility to analyze the occurrence of plasmid-mediated quinolone resistance (PMQR) and oqx genes and their implications for quinolone susceptibility. The oqxA and oqxB genes were found in 31/34 (91%) Klebsiella pneumoniae and 1/3 Klebsiella oxytoca isolates. However, the oqxA - and oqxB -harboring isolates lacking other known quinolone resistance determinants showed wide ranges of susceptibility to nalidixic acid and ciprofloxacin. Sixty of the 105 isolates (57%) harbored at least one PMQR gene [ qnrB19 , qnrB10 , qnrB2 , qnrB1 , qnrS1 , or aac ( 6 ′) -Ib-cr )], belong to 8 enterobacterial species, and were disseminated throughout the country, and most of them were categorized as susceptible by the current clinical quinolone susceptibility breakpoints. We developed a disk diffusion-based method to improve the phenotypic detection of aac ( 6 ′) -Ib-cr . The most common PMQR genes in our collection [ qnrB19 , qnrB10 , and aac ( 6 ′) -Ib-cr ] were differentially distributed among enterobacterial species, and two different epidemiological settings were evident. First, the species associated with community-acquired infections ( Salmonella spp. and Escherichia coli ) mainly harbored qnrB19 (a unique PMQR gene) located in small ColE1-type plasmids that might constitute its natural reservoirs. qnrB19 was not associated with an extended-spectrum β-lactamase phenotype. Second, the species associated with hospital-acquired infections ( Enterobacter spp., Klebsiella spp., and Serratia marcescens ) mainly harbored qnrB10 in IS CR1 -containing class 1 integrons that may also have aac ( 6 ′) -Ib-cr as a cassette within the variable region. These two PMQR genes were strongly associated with an extended-spectrum β-lactamase phenotype. Therefore, this differential distribution of PMQR genes is strongly influenced by their linkage or lack of linkage to integrons.