title: Co-existence of plasmid-mediated quinolone resistance determinants and mutations in gyrA and parC among fluoroquinolone-resistant clinical Enterobacteriaceae isolated in a tertiary hospital in Warsaw, Poland.
abstract: Plasmid-mediated quinolone resistance (PMQR) determinants and the distribution of mutations in the quinolone resistance-determining regions (QRDRs) of gyrA and parC were investigated in 215 ciprofloxacin-resistant (MIC>1mg/L) clinical Enterobacteriaceae collected during a 6-month prospective study in a tertiary hospital in Warsaw, Poland. PMQR determinants were present in 49 isolates (22.8%), among which aac(6')-Ib-cr and qnrB1 predominated (85.7% and 26.5%, respectively). Mutations in gyrA and parC QRDRs were detected among 89.8% of isolates (MIC≥4mg/L). Changes in Ser-83, Ala-84 and Asp-87 in GyrA and Ser-80 and Glu-84 in ParC were detected. Five isolates with ciprofloxacin MICs in the range 1.5-16 mg/L were found to have unaltered QRDRs, with PMQR as the only fluoroquinolone (FQ) resistance trait detected. The remaining 44 PMQR-positive isolates were found to carry altered QRDRs. Three substitutions (two in GyrA and one in ParC) were detected in 23 isolates, whilst 8 isolates carried four mutations (two in GyrA and two in ParC). One isolate of Klebsiella pneumoniae with two amino acid substitutions in the ParC QRDR in the presence of aac(6')-Ib-cr and qnrB1 had a ciprofloxacin MIC of 16mg/L. The results presented here show that FQ resistance in these clinical Enterobacteriaceae is a complex interplay between PMQR determinants and mutations in gyrA and parC rather than a single stepwise accumulation of mutations in the gyrase and topoisomerase subunits. In addition, these results show the role of PMQR determinants in promoting QRDR mutations and the acquisition of high-level FQ resistance in clinical settings.
authors.affiliation: Department of Bacteriology, National Institute of Public Health - National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland. Electronic address: kpiekarska@pzh.gov.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Piekarska
authors.affiliation: Department of Bacteriology, National Institute of Public Health - National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wołkowicz
authors.affiliation: Department of Bacteriology, National Institute of Public Health - National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Zacharczuk
authors.affiliation: Department of Bacteriology, National Institute of Public Health - National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Rzeczkowska
authors.affiliation: Department of Bacteriology, National Institute of Public Health - National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Chróst
authors.affiliation: Department of Laboratory Diagnostics, Military Institute of Medicine, Szaserów 128, 04-141 Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Bareja
authors.affiliation: Department of Laboratory Diagnostics, Military Institute of Medicine, Szaserów 128, 04-141 Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Olak
authors.affiliation: Department of Bacteriology, National Institute of Public Health - National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Gierczyński
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics* / Q000378:metabolism; D027101:DNA Topoisomerase IV / Q000235:genetics*; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D050505:Mutant Proteins / Q000235:genetics; D010957:Plasmids; D011044:Poland; D011446:Prospective Studies; D015363:Quinolones / Q000494:pharmacology*; D062606:Tertiary Care Centers
chemical_list: D000900:Anti-Bacterial Agents; D050505:Mutant Proteins; D015363:Quinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase
keywords: Enterobacteriaceae; PMQR; Poland; QRDR mutations