title: Frequent detection of plasmid-mediated quinolone resistance (qnr) genes in multidrug-resistant Enterobacteriaceae blood isolates, Hong Kong.
abstract: Plasmid-mediated quinolone resistance (qnr) genes confer low-level resistance but provide background for selection of highly-resistant strains. We investigated their prevalence and significance in clinical Enterobacteriaceae bacteremic isolates in Hong Kong. A prospective, hospital-based study was conducted (January 2008 to March 2009). Consecutive, non-duplicate blood isolates of extended-spectrum-β-lactamase (ESBL) and/or plasmid-mediated AmpC (PMAmpC) β-lactamase-producing Enterobacteriaceae were collected and subjected to qnr genes detection using multiplex PCR. Direct sequencing was performed to characterize the qnr and the co-existing bla genes. Clinical and microbiological variables, including antimicrobial resistance profiles, were compared between infections by 'qnr-positive' and 'qnr-negative' Enterobacteriaceae. Altogether 199 ESBL/PMAmpC-producing Enterobacteriaceae isolates were studied. qnr genes were detected in 20 % (qnrB, n = 24; qnrS, n = 16; qnrA, n = 0), of which 85% were Klebsiella spp. There was a strong association with PMAmpC genes (qnrB and DHA-1; p < 0.001). 'qnr-positive' isolates were more commonly hospital-acquired (60.0% vs 35.8%; adjusted OR 2.68, 95%CI 1.32-5.46) and multidrug-resistant (e.g. amoxicillin-clavulanate 90-100%, piperacillin-tazobactam 40-57%, ceftazidime 53-78%; sulfamethoxazole/trimethoprim 60-70%; ciprofloxacin 53-65%, levofloxacin 35-48%). Patients with 'qnr-positive' Enterobacteriaceae bacteremia had a higher 30-day mortality (45% vs 22%, p = 0.003). High Pitt bacteremia score, development of pneumonia, and failure to receive susceptible fluoroquinolone (adjusted HR 4.27; 95%CI 1.45-12.61) or carbapenem (adjusted HR 3.04; 95%CI 1.49-6.20) treatment were independent factors associated with death. A high proportion of ESBL/PMAmpC-producing Enterobacteriaceae (typically Klebsiella) bacteremic isolates carried qnr. These strains were multidrug-resistant, which was associated with inappropriate treatment and high fatality. Further dissemination of qnr and selection of fluoroquinolone/β-lactam-resistant strains should be closely monitored and controlled.
authors: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, 9/F, Clinical Sciences Building, Shatin, Hong Kong SAR, China.
authors: C C
authors: CC
authors: Lee
authors: G
authors: G
authors: Lui
authors: M
authors: M
authors: Ip
authors: T K W
authors: TK
authors: Ling
authors: N
authors: N
authors: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015331:Cohort Studies; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000453:epidemiology* / Q000382:microbiology; D005260:Female; D005798:Genes, Bacterial; D006723:Hong Kong / Q000453:epidemiology; D006761:Hospitals; D006801:Humans; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D010957:Plasmids; D015995:Prevalence; D011446:Prospective Studies; D015363:Quinolones / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D015363:Quinolones