Shin So Youn, Kwon Kye Chul, Park Jong Woo, Song Jeong Hoon, Ko Young Hyun, Sung Ji Youn, Shin Hae Won, Koo Sun Hoe
Department of Laboratory Medicine, Chungnam National University College of Medicine, Daejeon, Korea.
Korean J Lab Med. 2009 Dec;29(6):541-50. doi: 10.3343/kjlm.2009.29.6.541.
Concomitant quinolone resistance in extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is a crucial problem in the clinical management of infections. In foreign countries, the fluoroquinolone acetylating aminoglycoside-(6)-N-acetyltransferase (aac[6']-Ib-cr) gene, a novel plasmid-mediated quinolone resistance determinant has been reported to occur in conjunction with qnr. We aim to investigate the prevalence and characteristics of concomitant aac(6')-Ib-cr and qnr expression in ESBL-producing Escherichia coli and Klebsiella pneumoniae in Korea.
Between December 2007 and April 2008, we collected 60 and 69 clonally unrelated non-repetitive clinical isolates of ESBL-producing E. coli and K. pneumoniae, respectively. We studied the expressions of 11 types of ESBL-encoding genes, 4 types of 16s rRNA methylase genes; rmtA, rmtB, rmtC and armA, 3 types of qnr genes; qnrA, qnrB, qnrS and aac(6')-Ib. The presence of aac(6')-Ib-cr variants was detected by sequencing. The involvement of integrons was studied using multiplex PCR and sequencing of gene-cassette arrays. Conjugation experiments were performed to confirm plasmid-mediated resistance and the relationships among co-harbored genes.
We observed a high prevalence of the cr variant (61.1%) of aac(6')-Ib, and the prevalence of this variant in qnr and aac(6')-Ib-co-harboring isolates (67.4%) was higher than in qnr-negative isolates (51.7%). The high prevalence of the cr variant was significantly related to the high minimum inhibitory concentrations (MICs) of ciprofloxacin, tobramycin, and amikacin and indicated the statistically significant roles of qnrB, qnrS, rmtA, and rmtB in quinolone and aminoglycoside resistance.
The aac(6')-Ib-cr variants were widespread and showed significant relation to the high-level quinolone and aminoglycoside resistance in ESBL-producing E. coli and K. pneumoniae.
产超广谱β-内酰胺酶（ESBL）的肠杆菌科细菌中喹诺酮类药物的同时耐药是感染临床管理中的一个关键问题。在国外，氟喹诺酮乙酰化氨基糖苷-（6）-N-乙酰基转移酶（aac[6']-Ib-cr）基因，一种新型的质粒介导的喹诺酮耐药决定簇，已被报道与qnr同时出现。我们旨在调查韩国产ESBL的大肠埃希菌和肺炎克雷伯菌中aac(6')-Ib-cr和qnr共表达的流行情况及特征。
在2007年12月至2008年4月期间，我们分别收集了60株和69株产ESBL的大肠埃希菌和肺炎克雷伯菌的非克隆相关、非重复临床分离株。我们研究了11种ESBL编码基因、4种16s rRNA甲基化酶基因（rmtA、rmtB、rmtC和armA）、3种qnr基因（qnrA、qnrB、qnrS）和aac(6')-Ib的表达情况。通过测序检测aac(6')-Ib-cr变体的存在。使用多重PCR和基因盒阵列测序研究整合子的参与情况。进行接合实验以确认质粒介导的耐药性以及共携带基因之间的关系。
我们观察到aac(6')-Ib的cr变体（61.1%）的高流行率，并且该变体在qnr和aac(6')-Ib共携带分离株中的流行率（67.4%）高于qnr阴性分离株（51.7%）。cr变体的高流行率与环丙沙星、妥布霉素和阿米卡星的高最低抑菌浓度（MIC）显著相关，并表明qnrB、qnrS、rmtA和rmtB在喹诺酮类和氨基糖苷类耐药中具有统计学意义的作用。
aac(6')-Ib-cr变体广泛存在，并与产ESBL的大肠埃希菌和肺炎克雷伯菌的高水平喹诺酮类和氨基糖苷类耐药显著相关。
