Prevalence and diversity of qnr alleles in AmpC-producing Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii and Serratia marcescens: A multicentre study from Korea

Objectives: To investigate the prevalence of qnr determinants, their influence on quinolone susceptibility and their association with other plasmid-mediated genes in AmpC-producing Enterobacteriaceae without any selection criteria. Methods: A total of 644 consecutive, non-duplicate isolates of Enterobacter cloacae (186), Enterobacter aerogenes (154), Citrobacter freundii (138) and Serratia marcescens (166) were examined. We performed antimicrobial susceptibility testing and PCR for qnr determinants (qnrA, qnrB and qnrS), extended-spectrum β-lactamase (ESBL) (bla_TEM, bla_SHV and bla_CTX-M), orf513, orf1005 and bla_DHA-1 To differentiate qnr subtypes, restriction enzyme analysis and sequencing was performed. Results: The prevalence of qnr determinants was high in C. freundii (38.4%) and E. cloacae (28.5%), but low in E. aerogenes (3.2%) and S. marcescens (2.4%). qnrA1 was most frequent in E. cloacae, and qnrB was prevalent in C. freundii. All the qnrA- and qnrB4-positive isolates showed ciprofloxacin MICs ≥ 0.5 mg/L and nalidixic acid MICs ≥ 16 mg/L. However, the B1 and B2 subtypes showed a wide range of quinolone MICs. In relation to ESBLs, we found that qnrA1, qnrB2 and qnrB4 producers were significantly more frequent among ESBL producers (P< 0.05). Twelve of 13 qnrB4 producers harboured bla_DHA-1. orf513 was detected in 43 isolates of the 47 isolates with co-resident qnr and ESBL genes. None of the qnr producers harboured orf1005. Conclusions: The prevalence of qnrA and qnrB was high among C. freundii and E. cloacae in Korea and there were characteristics unique to the qnr subtypes. Quinolones should be used cautiously in these species, especially when they are ESBL producers.