Wueppenhorst Nicole, Stueger Hans-Peter, Kist Manfred, Glocker Erik
National Reference Centre for Helicobacter pylori, Department of Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Hospital Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany.
J Antimicrob Chemother. 2009 Apr;63(4):648-53. doi: 10.1093/jac/dkp003. Epub 2009 Feb 3.
The aim of this study was to estimate the frequency of triple- and quadruple-resistant Helicobacter pylori isolated in Germany, to characterize those isolates molecular genetically and to identify risk factors for the development of multiresistance.
Antimicrobial susceptibility to metronidazole, clarithromycin, amoxicillin, tetracycline, ciprofloxacin/levofloxacin and rifampicin in 1118 clinical isolates obtained between July 2006 and December 2007 was tested by the Etest method. For patients harbouring triple- or quadruple-resistant strains (n = 169), data on prior eradication therapies and underlying diseases were collected and evaluated. A select number of quadruple- and triple-resistant strains were examined for resistance-mediating mutations in their 23S rRNA, 16S rRNA, gyrA and rpoB genes, respectively.
From 1118 clinical isolates, 13.4% (n = 150) showed phenotypic resistance to metronidazole, clarithromycin and quinolones and 0.9% (n = 10) to metronidazole, clarithromycin and rifampicin; one isolate exhibited resistance to clarithromycin, quinolones and rifampicin. In eight isolates (0.7%), we detected phenotypic quadruple resistance to metronidazole, clarithromycin, quinolones and rifampicin or tetracycline. Triple- and quadruple-resistant strains harboured resistance-associated mutations in their 23S rRNA, 16S rRNA, gyrA or rpoB genes and were nearly exclusively isolated from patients who had already been unsuccessfully treated on multiple occasions.
We show that more than 15% of H. pylori strains isolated from routine samples in the German National Reference Centre are resistant to three or more antimicrobials and identified prior unsuccessful eradication therapies as a key factor for the development of multiresistance. Our data emphasize the need for further comprehensive surveillance studies monitoring the role of treatment regimens in antimicrobial resistance in H. pylori.
本研究旨在评估德国分离出的对三联和四联抗菌药物耐药的幽门螺杆菌的频率，从分子遗传学角度对这些分离株进行特征分析，并确定多药耐药发生的危险因素。
采用Etest法检测了2006年7月至2007年12月间获得的1118株临床分离株对甲硝唑、克拉霉素、阿莫西林、四环素、环丙沙星/左氧氟沙星和利福平的药敏情况。对于携带三联或四联耐药菌株的患者（n = 169），收集并评估了其既往根除治疗和基础疾病的数据。分别对部分四联和三联耐药菌株的23S rRNA、16S rRNA、gyrA和rpoB基因进行耐药介导突变检测。
在1118株临床分离株中，13.4%（n = 150）对甲硝唑、克拉霉素和喹诺酮类药物表现出表型耐药，0.9%（n = 10）对甲硝唑、克拉霉素和利福平耐药；1株对克拉霉素、喹诺酮类药物和利福平耐药。在8株（0.7%）中，检测到对甲硝唑、克拉霉素、喹诺酮类药物和利福平或四环素的表型四联耐药。三联和四联耐药菌株在其23S rRNA、16S rRNA、gyrA或rpoB基因中存在耐药相关突变，且几乎均从多次治疗失败的患者中分离得到。
我们发现，德国国家参考中心从常规样本中分离出的幽门螺杆菌菌株中，超过15%对三种或更多抗菌药物耐药，并确定既往根除治疗失败是多药耐药发生的关键因素。我们的数据强调需要进一步开展全面的监测研究，以监测治疗方案在幽门螺杆菌抗菌药物耐药中的作用。
