The purpose of this study was to determine prevalence and molecular characterization of plasmid-mediated quinolone resistance (PMQR) genes [qnrA, qnrB, qnrC, qnrD, qnrS, aac(6′)-Ib-cr, qepA, and oqxAB] among extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella spp. isolates from bloodcultures in Hungary. A total of 103 isolates were tested for quinolone susceptibility by microdilution method and PMQR genes were detected by polymerase chain reaction. About 40 ESBL-producing E. coli (39%) and 50 ESBL-producing Klebsiella spp. strains (48%) were resistant to ciprofloxacin; 40 ESBL-producing E. coli (39%) and 47 ESBL-producing Klebsiella spp. strains (45%) were resistant to levofloxacin; and 88 strains including 40 ESBL-producing E. coli (39%) and 48 (47%) ESBL-producing Klebsiella spp. were resistant to moxifloxacin. Among the 103 ESBL-producing isolates, 77 (75%) isolates (30 E. coli and 47 Klebsiella spp.) harbored PMQR genes. The most commonly detected gene was aac(6′)-Ib-cr (65%). The occurrence of qnrS gene was 6%. Interestingly, qnrA, qnrB, qnrC, qnrD, and qepA were not found in any isolates. Among 77 PMQR-positive isolates, 27 (35.1%) and 1 (1.3%) carried two and three different PMQR genes, respectively. Only Klebsiella spp. harbored more than one PMQR genes. Observing prevalence of PMQR genes in the last 8 years, the increasing incidence of aac(6′)-Ib-cr and oqxAB can be seen. Our results highlight high frequency of PMQR genes among ESBL-producing Klebsiella pneumoniae and E. coli isolates with an increasing dynamics in Hungary.
Robicsek, A., Jacoby, G. A., Hooper, D. C.: The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis 6, 629–640 (2006).
Levine, C., Hiasa, H., Marians, K. J.: DNA gyrase and topoisomerase IV: Biochemical activities, physiological roles during chromosome replication, and drug sensitivities. Biochim Biophys Acta 1400, 29–43 (1998).
Jacoby, G. A.: Mechanisms of resistance to quinolones. Clin Infect Dis 41, 120–126 (2005).
Huang, W. M.: Bacterial diversity based on type II DNA topoisomerase genes. Annu Rev Genet 30, 79–107 (1996).
Mazzariol, A., Zuliani, J., Cornaglia, G., Rossolini, G. M., Fontana, R.: AcrAB efflux system: Expression and contribution to fluoroquinolone resistance in Klebsiella spp. Antimicrob Agents Chemother 46, 3984–3986 (2002).
EUCAST: http:\\www.eucast.org.
CLSI: http:\\www.clsi.org.
Martinez-Martinez, L., Pascual, A., Jacoby, G. A.: Quinolone resistance from a transferable plasmid. Lancet 14, 797–799 (1998).
Rodríguez-Martínez, J. M., Cano, M. E., Velasco, C., Martínez-Martínez, L., Pascual, A.: Plasmid-mediated quinolone resistance: An update. J Infect Chemother 17, 149–182 (2011).
Kocsis, B., Kocsis, E., Fontana, R., Cornaglia, G., Mazzariol, A.:Identification of bla LAP-2 and qnrS1 genes in the internationally successful Klebsiella pneumoniae ST147 clone. J Med Microbiol 62, 269–273 (2013).
Robicsek, A., Strahilevitz, J., Sahm, D. F., Jacoby, G. A., Hooper, D. C.: qnr Prevalence in ceftazidime-resistant Enterobacteriaceae isolates from the United States. Antimicrob Agents Chemother 50, 2872–2874 (2006).
Jacoby, G. A., Walsh, K. E., Mills, D. M., Walker, V. J., Oh, H., Robicsek, A., Hooper, D. C.: qnrB, another plasmid-mediated gene for quinolone resistance. Antimicrob Agents Chemother 50, 1178–1182 (2006).
Wang, M., Guo, Q., Xu, X., Wang, X., Ye, X., Wu, S., Hooper, D. C.: New plasmid-mediated quinolone resistance gene, qnrC, found in a clinical isolate of Proteus mirabilis. Antimicrob Agents Chemother 53, 1892–1897 (2009).
Cavaco, L. M., Hasman, H., Xia, S., Aarestrup, F. M.: qnrD, a novel gene conferring transferable quinolone resistance in Salmonella enterica serovars Kentucky and Bovismorbificans of human origin. Antimicrob Agents Chemother 53, 603–608 (2009).
Park, C. H., Robicsek, A., Jacoby, G. A., Sahm, D., Hooper, D. C.: Prevalence in the United States of aac(6)-Ib-cr encoding a ciprofloxacin-modifying enzyme. Antimicrob Agents Chemother 50, 3953–3955 (2006).
Kim, H. B., Wang, M., Park, C. H., Kim, E. C., Jacoby, G. A., Hooper, D. C.: oqxAB encoding a multidrug efflux pump in human clinical isolates of Enterobacteriaceae. Antimicrob Agents Chemother 53, 3582–3584 (2009).
Yamane, K., Wachino, J., Suzuki, S., Arakawa, Y.: Plasmid-mediated qepA gene among Escherichia coli clinical isolates from Japan. Antimicrob Agents Chemother 52, 1564–6 (2008).
Szabó, D., Kocsis, B., Rókusz, L., Szentandrássy, J., Katona, K., Kristóf, K., Nagy, K.: First detection of plasmid-mediated, quinolone resistance determinants qnrA, qnrB, qnrS and aac(6′)-Ib-cr in extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Budapest, Hungary. J Antimicrob Chemother 62, 630–632 (2008).
Yang, H., Chen, H., Yang, Q., Chen, M., Wang, H.: High prevalence of plasmid-mediated quinolone resistance genes qnr and aac(6′)-Ib-cr in clinical isolates of Enterobacteriaceae from nine teaching hospitals in China. Antimicrob Agents Chemother 52, 4268–4273 (2008).
Anuar, A. S. S., Yusof, M. Y. M., Tay, S. T.: Prevalence of plasmid-mediated qnr determinants and gyrase alteration in Klebsiella pneumoniae isolated from a university teaching hospital in Malaysia. Eur Rev Med Pharmacol Sci 17, 1744–1747 (2013).
Wang, M., Sahm, D. F., Jacoby, G. A., Hooper D. C. : Emerging plasmid-mediated quinolone resistance associated with the qnr gene in Klebsiella pneumoniae clinical isolates in the United States. Antimicrob Agents Chemother 48, 1295–1299 (2004).
Teo, J. W. P., Ng, K. Y., Lin, R. T. P.: Detection and genetic characterisation of qnrB in hospital isolates of Klebsiella pneumoniae in Singapore. Int J Antimicrob Agents 33, 177–180 (2009).
Kocsis, B., Mazzariol, A., Kocsis, E., Koncan, R., Fontana, R., Cornaglia, G.: Prevalence of plasmid-mediated quinolone resistance determinants in Enterobacteriaceae strains isolated in North-East Italy. J Chemother 25, 36–40 (2013).
Minarini, L. A. R., Poirel, L., Cattoir, V., Darini, A. L. C., Nordmann, P.: Plasmid-mediated quinolone resistance determinants among enterobacterial isolates from outpatients in Brazil. J Antimicrob Chemother 62, 474–478 (2008).
Mazzariol, A., Kocsis, B., Koncan, R., Kocsis, E., Lanzafame, P., Cornaglia, G.: Description and plasmid characterization of qnrD determinants in Proteus mirabilis and Morganella morganii. Clin Microbiol Infect 18, 46–48 (2012).
Guillard, T., Grillon, A., de Champs, C., Cartier, C., Madoux, J., Berçot, B., Lebreil, A. L., Lozniewski, A., Riahi, J., Vernet-Garnier, V., Cambau, E.: Mobile insertion cassette elements found in small non-transmissible plasmids in Proteeae may explain qnrD mobilization. PLoS One 9, 87801 (2014).
Shams, E., Firoozeh, F., Moniri, R., Zibaei, M.: Prevalence of plasmid-mediated quinolone resistance genes among extended-spectrum β -Lactamase-producing Klebsiella pneumoniae human isolates in Iran. J Pathog 434391 (2015).
Briales, A., Rodríguez-Martínez, J. M., Velasco, C., de Alba, P. D., Rodríguez-Baño, J., Martínez-Martínez, L., Pascual, A.: Prevalence of plasmid-mediated quinolone resistance determinants qnr and aac(6′)-Ib-cr in Escherichia coli and Klebsiella pneumoniae producing extended-spectrum β-lactamases in Spain. Int J Antimicrob Agents 39, 431–434 (2012).
Hansen, L. H., Jensen, L. B., Sorensen, H. I., Sorensen, S. J.: Substrate specificity of the OqxAB multidrug efflux pump in Escherichia coli and selected enteric bacteria. J Antimicrob Chemother 60, 145–147 (2007).
Rodríguez-Martínez, J. M., de Alba, P. D., Briales, A., Machuca, J., Lossa, M., Fernández-Cuenca, F., Rodríguez Baño, J., Martínez-Martínez, L., Pascual, Á.: Contribution of OqxAB efflux pumps to quinolone resistance in extended-spectrum-β-lactamase-producing Klebsiella pneumoniae. J Antimicrob Chemother 68, 68–73 (2013).
Yuan, J., Xu, X., Guo, Q., Zhao, X., Ye, X., Guo, Y., Wang, M.: Prevalence of the oqxAB gene complex in Klebsiella pneumoniae and Escherichia coli clinical isolates. J Antimicrob Chemother 67, 1655–1659 (2012).
Ferjani, S., Saidani, M., Amine, F. S., Boutiba-Ben Boubaker, I.: Prevalence and characterization of plasmid-mediated quinolone resistance genes in extended-spectrum β-lactamase-producing Enterobacteriaceae in a Tunisian hospital. Microb Drug Resist 21, 158–66 (2015).
Füzi, M.: Has the use of fluoroquinolones facilitated the widespread dissemination of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase producing Klebsiella pneumoniae in the health care setting? Acta Microbiol Immunol Hung 61, 399–405 (2014).
Melegh, S., Schneider, G., Horváth, M., Jakab, F., Emődy, L., Tigyi, Z.: Identification and characterization of CTX-M-15 producing Klebsiella pneumoniae clone ST101 in a Hungarian university teaching hospital. Acta Microbiol Immunol Hung 62, 233–245 (2015).
Szabo, R., Böröcz, K.: Infections and antimicrobial use among institutionalized residents in Hungary: Increasing need of microbiological surveillance. Acta Microbiol Immunol Hung 62, 29–44 (2015).
Somily, A. M., Garaween, G. A., Abukhalid, N., Absar, M. M., Senok, A. C.: Comparison of molecular and phenotypic methods for the detection and characterization of carbapenem resistant Enterobacteriaceae. Acta Microbiol Immunol Hung 63, 69–81 (2016).