Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Int J Antimicrob Agents. 2010 Apr;35(4):387-91. doi: 10.1016/j.ijantimicag.2009.12.005.
Fluoroquinolone (FQ) resistance is usually caused by point mutations within the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and/or parE. However, little is known about the worldwide increase in FQ-resistant Escherichia coli or, more specifically, about the geographical distribution of QRDR mutations and the clonal spread of isolates. In this study, we analysed 68 FQ-resistant E. coli isolates from eight Asian countries using QRDR amino acid mutation patterns and examined their susceptibility to FQs. Of the isolates, 38% had mutations at S83 and D87 of GyrA and S80 of ParC (MM/-/M-/-) and 34% had mutations at S83 and D87 of GyrA, S80 of ParC and S458 of ParE (MM/-/M-/M). MIC(50) values (minimum inhibitory concentrations for 50% of the isolates) for isolates with at least mutation at S458 of ParE for ciprofloxacin and prulifloxacin were relatively higher than MIC(50) values of isolates without this mutation. Based on their geographic distribution and the QRDR mutation patterns, the isolates were divided into a common type in which the organisms were isolated from three or more countries, and a local type in which the isolates were from one or two countries. Mutation types at S83L and D87N in GyrA and S80I in ParC with no or another site in the QRDR were the most frequent among the FQ-resistant isolates, especially among the common type. Gene typing indicated that isolates in the common type were not similar between countries. These data suggest that the increase in FQ-resistant E. coli strains is mainly generated by mutations in the QRDR in each geographical area rather than through intercontinental spread.
氟喹诺酮（FQ）耐药性通常是由喹诺酮耐药决定区（QRDR）中gyrA、gyrB、parC 和/或 parE 的点突变引起的。然而，对于世界范围内 FQ 耐药大肠杆菌的增加，或者更具体地说，对于 QRDR 突变的地理分布和分离株的克隆传播，了解甚少。在这项研究中，我们使用 QRDR 氨基酸突变模式分析了来自八个亚洲国家的 68 株 FQ 耐药大肠杆菌，并检查了它们对 FQ 的敏感性。在这些分离株中，38%的分离株在 GyrA 的 S83 和 D87 以及 ParC 的 S80 处发生突变（MM/-/M-/-），34%的分离株在 GyrA 的 S83 和 D87、ParC 的 S80 和 ParE 的 S458 处发生突变（MM/-/M-/M）。对于至少在 ParE 的 S458 处发生突变的环丙沙星和普卢利沙星的分离株，MIC50（分离株的 50%最小抑菌浓度）值相对较高，而没有这种突变的分离株的 MIC50 值较低。根据它们的地理分布和 QRDR 突变模式，将分离株分为常见型，即从三个或更多国家分离到的分离株，以及本地型，即从一个或两个国家分离到的分离株。在 GyrA 的 S83L 和 D87N 以及 ParC 的 S80I 处发生突变，QRDR 中没有或发生其他部位的突变类型是 FQ 耐药分离株中最常见的突变类型，尤其是在常见型中。基因分型表明，常见型的分离株在国家之间并不相似。这些数据表明，FQ 耐药大肠杆菌菌株的增加主要是由每个地理区域的 QRDR 突变产生的，而不是通过洲际传播产生的。
