Ziver-Sarp Tevhide, Yuksel-Mayda Pelin, Saribas Suat, Demiryas Suleyman, Gareayaghi Nesrin, Ergin Sevgi, Tasci Ihsan, Ozbey Dogukan, Bal Kadir, Erzin Yusuf, Akkus Seher, Bahar-Tokman Hrisi, Demirci Mehmet, Tufan-Kocak Banu, Kocazeybek Bekir
Clin Lab. 2021 Oct 1;67(10). doi: 10.7754/Clin.Lab.2021.210843.
Spontaneous point mutations in genes encoding gyrA/B subunits of DNA gyrase are responsible for fluoroquinolone resistance. We aimed to determine the clarithromycin and levofloxacin resistance phenotypically in H. pylori strains and to investigate the mutations responsible for levofloxacin resistance and the effects of these mutations on dual antibiotic resistance.
A total of 65 H. pylori isolates were included. The E-test method was used for the clarithromycin and le-vofloxacin antimicrobial susceptibility test. Real-time PCR was used to detect the point mutations.
Twenty-four (36.9%) of 65 H. pylori strains were phenotypically resistant to clarithromycin and 14 (21.5%) to levofloxacin. The phenotypic levofloxacin resistance rate of strains with Asn87Lys and Asp91Asn mutations were significantly higher (gyrA gene) (p < 0.05). The phenotypic levofloxacin resistance rate of strains with Arg484Lys and Asp481Glu mutations were significantly higher (gyrB gene) (p < 0.05). The Asn87Lys mutation increased the risk of phenotypes being resistant to levofloxacin 70.156 times and Asp91Asn mutation increased 125,427 times higher. Seven (10.8%) of 65 H. pylori strains showed dual resistance to both levofloxacin and clarithromycin. The rate of being dual resistant with A2143G mutation (clarithromycin resistance) was found to be significantly higher (p < 0.05).
The Asn87Lys and Asp91Asn mutations in the gyrA gene had a phenotypically enhancing effect on levofloxacin resistance, while the presence of Asp481Glu and Arg484Lys mutations in the gyrB gene did not. The existence of dual resistance was developed with the increase in clarithromycin and levofloxacin resistance rates.
编码DNA旋转酶A/B亚基的基因发生自发点突变会导致对氟喹诺酮类药物产生耐药性。我们旨在从表型上确定幽门螺杆菌菌株对克拉霉素和左氧氟沙星的耐药性，并研究导致左氧氟沙星耐药的突变及其对双重抗生素耐药性的影响。
共纳入65株幽门螺杆菌分离株。采用E-test法进行克拉霉素和左氧氟沙星抗菌药敏试验。采用实时荧光定量PCR检测点突变。
65株幽门螺杆菌菌株中，24株（36.9%）对克拉霉素表型耐药，14株（21.5%）对左氧氟沙星表型耐药。携带Asn87Lys和Asp91Asn突变的菌株（gyrA基因）对左氧氟沙星的表型耐药率显著更高（p<0.05）。携带Arg484Lys和Asp481Glu突变的菌株（gyrB基因）对左氧氟沙星的表型耐药率显著更高（p<0.05）。Asn87Lys突变使对左氧氟沙星表型耐药的风险增加70.156倍，Asp91Asn突变增加125427倍。65株幽门螺杆菌菌株中有7株（10.8%）对左氧氟沙星和克拉霉素均耐药。发现携带A2143G突变（克拉霉素耐药）的双重耐药率显著更高（p<0.05）。
gyrA基因中的Asn87Lys和Asp91Asn突变对左氧氟沙星耐药性具有表型增强作用，而gyrB基因中Asp481Glu和Arg484Lys突变则没有。随着克拉霉素和左氧氟沙星耐药率的增加，出现了双重耐药性。
