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Antimicrobial Agents and Chemotherapy, May 2005, p. 2146-2147, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.2146-2147.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

LETTER TO THE EDITOR

Further Identification of Plasmid-Mediated Quinolone Resistance Determinant in Enterobacteriaceae in Turkey


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LETTER
 
Quinolone resistance arises mostly from chromosomal mutations in genes coding for DNA gyrase (topoisomerase II) and genes coding for outer membrane proteins in members of the family Enterobacteriaceae (6). However, plasmid-mediated resistance to quinolones has been reported in 1998 from a Klebsiella pneumoniae strain isolated from Birmingham, Ala. (3). This determinant, named Qnr (and recently renamed QnrA according to G. A. Jacoby's suggestion), is a 218-amino-acid protein that binds to subunits of the DNA gyrase, preventing further binding of quinolones (7, 8). QnrA confers resistance to nalidixic acid and increases the MICs of fluoroquinolones by four- to eightfold (10). Published data report the spread of qnr-positive enterobacterial isolates mostly from the United States, Southeast Asia, and more recently from Europe (1-3, 9, 11). Several qnrA-like-positive enterobacterial isolates produced clavulanic acid-inhibited extended-spectrum ß-lactamases (ESBLs) (1, 2, 9, 11). Thus, we have screened for qnrA-like genes in nalidixic acid-resistant and ESBL-positive enterobacterial isolates from the university hospital of Istanbul in Turkey, a country located between Europe and Asia.

Screening was performed among nonclonally strains distributed as follows: six Escherichia coli isolates and one Klebsiella pneumoniae isolate from 2002; two E. coli isolates and one K. pneumoniae isolate from 2003; and 28 E. coli isolates, five K. pneumoniae isolates, four Enterobacter cloacae isolates, and two Citrobacter freundii isolates from 2004. Out of a total of 49 ESBL-positive strains, two strains (E. cloacae 14300 and C. freundii Lut) (4%) were positive for qnrA-like genes using PCR technique and detection primers, as reported previously (2). E. cloacae 14300 was from a skin abscess of a 33-year-old injured male, whereas C. freundii LUT was from an urinary tract infection of a 63-year-old male after 12 days of treatment with ciprofloxacin. A quinolone resistance determinant from fluoroquinolone-resistant clinical strains was transferred by conjugation using E. coli strain J53 that was resistant to azide, as detailed previously (2). According to disk diffusion susceptibility testing and MIC determinations (4), E. cloacae transconjugants were resistant to nalidixic acid, chloramphenicol, tetracycline, kanamycin, tobramycin, streptomycin, sulfamides, and trimethoprim, whereas C. freundii transconjugants were also resistant to gentamicin and rifampin. Transconjugants and clinical isolates had an ESBL-positive resistance profile that caused us to analyze their ß-lactamase and plasmid content also using a series of techniques reported elsewhere (2, 5). E. cloacae 14300 harbored the QnrA determinant as previously reported (7) located on a 50-kb conjugative plasmid in association with the blaSHV-5 gene, whereas C. freundii Lut harbored two plasmids of 170 and 80 kb. In the latter case, the 170-kb conjugative plasmid harbored a qnrA gene, a blaVEB-1 ESBL gene, whereas the nonconjugative 80-kb plasmid harbored the blaOXA-48 ß-lactamase gene. In both cases, the qnrA gene was preceded by the CR1 element containing the Orf513 and providing sequence promoters for its expression as demonstrated previously (2).

Identification of QnrA associated with SHV-5-like ESBL (SHV-7) was performed previously (9), whereas the ESBL VEB-1 has been identified recently from a QnrA-positive E. coli isolate from France (2). The carbapenem resistance of C. freundii Lut was explained by the production of a carbapenem-hydrolyzing ß-lactamase OXA-48 as reported initially in a K. pneumoniae isolate isolated from the same city (5).

From a general point of view, this report underlines the spread of a plasmid-mediated quinolone resistance determinant in Enterobacteriaceae with its peculiar association with ESBLs. It also identified ESBL VEB-1 from another part of the world. Interestingly, association of QnrA now with the powerful carbapenemase OXA-48 gives rise to an unknown level of multidrug resistance.


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ACKNOWLEDGMENTS
 
This work was funded by a grant from the Ministère de l'Education Nationale et de la Recherche (UPRES-EA3539), Université Paris XI, France, and by a grant from the European Community (6th PCRD, LSHM-CT-2003-503335).


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Hasan Nazic
Department of Microbiology
Istanbul Faculty of Medicine
Istanbul, Turkey

Laurent Poirel
Patrice Nordmann*
Service de Bactériologie-Virologie
Hôpital de Bicêtre
Assistance Publique/Hôpitaux de Paris
Faculté de Médecine Paris-Sud
Université Paris XI
94275 Le Kremlin-Bicêtre, France

* Phone: 33-1-45-21-36-32, Fax: 33-1-45-21-63-40, E-mail: nordmann.patrice{at}bct.ap-hop-paris.fr

Antimicrobial Agents and Chemotherapy, May 2005, p. 2146-2147, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.2146-2147.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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  • Tamang, M. D., Seol, S. Y., Oh, J.-Y., Kang, H. Y., Lee, J. C., Lee, Y. C., Cho, D. T., Kim, J. (2008). Plasmid-Mediated Quinolone Resistance Determinants qnrA, qnrB, and qnrS among Clinical Isolates of Enterobacteriaceae in a Korean Hospital. Antimicrob. Agents Chemother. 52: 4159-4162 [Abstract] [Full Text]  
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