Emerging Plasmid-Mediated Quinolone Resistance Associated with the qnr Gene in Klebsiella pneumoniae Clinical Isolates in the United States

Abstract

Although quinolone resistance commonly results from chromosomal mutation, recent studies indicate that such resistance can also be transferred on plasmids carrying the gene responsible, qnr. One hundred ten ciprofloxacin-resistant clinical isolates of Klebsiella pneumoniae and Escherichia coli from the United States were screened for the qnr gene by PCR and Southern hybridization of plasmid DNA. Conjugation experiments were done with azide-resistant E. coli J53 as the recipient and selection with azide and sulfonamide, a resistance frequently linked to qnr. EcoRI and BamHI digests of qnr-hybridizing plasmids were subjected to electrophoresis on agarose gels and probed with qnr by Southern hybridization. qnr was detected in 8 (11.1%) of 72 K. pneumoniae strains. These eight positive strains were from six states in the United States. qnr was not found in any of the 38 E. coli strains tested. Quinolone resistance was transferred from seven of the eight probe-positive strains. Transconjugants with qnr-hybridizing plasmids had 32-fold increases in ciprofloxacin MICs relative to E. coli J53. For all eight strains, the sequence of qnr was identical to that originally reported. By size and restriction digests, four plasmids were related to the first-reported plasmid, pMG252, and three were different. Five new qnr plasmids encoded FOX-5 ␤-lactamase, as did pMG252, but two others produced SHV-7 extended-spectrum ␤-lactamase. Transferable plasmid-mediated quinolone resistance associated with qnr is now widely distributed in quinolone-resistant clinical strains of K. pneumoniae in the United States. Plasmid-determined quinolone resistance contributes to the increasing quinolone resistance of K. pneumoniae isolates and to the linkage previously observed between resistance to quinolones and the latest ␤-lactam antibiotics.Quinolone resistance is usually caused by chromosomal mutations, but plasmid-mediated quinolone resistance has been discovered recently. The gene responsible for plasmid-mediated resistance, qnr, was found on plasmids varying in size from 54 to Ն180 kb in clinical isolates of Klebsiella pneumoniae and Escherichia coli from which low-level quinolone resistance could be transferred to a sensitive recipient by conjugation (11,19). Although our previous study showed that qnr was present in 8% of quinolone-resistant clinical isolates of E. coli from Shanghai, China (19), surveys for the presence of qnr are few, and in those few surveys qnr has rarely been found in clinical strains from other areas of the world (6, 15). More information on the prevalence of qnr in clinical strains is needed to understand its importance and contribution to the development of quinolone resistance.Our previous study found that qnr is located in complex In4 family class 1 integrons In36 and In37 (19), which are also known as complex sul1-type integrons because of the presence of duplicate qacE⌬1 and sul1genes. This relationship is supported by in vitro susceptibility results on transconjugants containing plasmids carrying qnr, showing...

Prevalence of qnr Genes and Antibiotic Susceptibility Patterns among Clinical Isolates of Klebsiella Pneumoniae in West of Iran

“…This rate of qnr prevalence was consistent with some studies carried out in Taiwan and the USA (15,16). Prevalence of qnr in the present study was also higher than that shown in other areas in Brazil (2.3%), Singapore (5.2%) and the USA (11.1%) [12,13,17]. In contrast, it was much lower than the prevalence of qnr genes detected in Malaysia (48.9%) and China (65.5%) [14,19].…”

“…Although the qnr gene indicates a low level of resistance to quinolones, its attendance aids the selection of chromosomal mutations, facilitating increased resistance in the host strain [9][10][11]. Frequency of qnr genes PMQR associated with the qnr genes in different human clinical enterobacterial isolates was determined first in the USA in 1994 using a K. pneumoniae isolate (later termed qnrA1) [9], which was then widely reported worldwide [12][13][14][15][16][17][18][19]. However, no study has been done on prevalence of qnr genes among enterobacterial clinical isolates in Iran.…”

Contribution of Multi‐Antimicrobial Resistance to the Population of Antimicrobial ResistantEscherichia coliIsolated from Apparently Healthy Pigs in Japan

“…Resistance to quinolones is mainly due to mutations in the quinoloneresistance determining region of DNA gyrase and topoisomerase IV (19). In Japan, there are no reports about plasmid-mediated quinolone resistance as reported in other countries (5,13,23,24). Hence, it is likely that the occurrence of resistance against nalidixic acid is not linked to the prevalence of multi-antimicrobial resistance.…”

Prevalence of Plasmids Mediated <i>Pseudomonas aeruginosa</i> Resistant Genes from Burn Wound Patients at the University of Benin Teaching Hospital Benin City, Nigeria

“…Conjugation was carried on the isolates; according to Wang et al 31 and Yutaka et al 36 with Ps. aeruginosa strain ATCC 10145 used as the recipient mating strains were incubated at 37°C for 18 hours without shaking.…”