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比较消化不良患者来源的幽门螺杆菌菌株中新的和经典的与克拉霉素耐药相关的点突变及其对表型克拉霉素耐药的影响。

Comparison of new and classical point mutations associated with clarithromycin resistance in Helicobacter pylori strains isolated from dyspeptic patients and their effects on phenotypic clarithromycin resistance.

机构信息

Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey.

Beykent University Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey.

出版信息

J Med Microbiol. 2019 Apr;68(4):566-573. doi: 10.1099/jmm.0.000944. Epub 2019 Feb 6.

Abstract

PURPOSE

We aimed to investigate the presence of three recently identified point mutations (A2115G, G2141A and A2144T) of the 23 S rRNA gene and compare them with the three most frequently encountered point mutations (A2142G, A2142C and A2143G) in Helicobacter pylori strains in Turkey.

METHODOLOGY

A total of 63 patients (mean 47.08±12.27) were included. The E-test method (for clarithromycin) was used for the clarithromycin antimicrobial susceptibility test of isolated H. pylori strains. Real-time PCR was used to detect the point mutations.

RESULTS

A total of 24 out of 63 H. pylori strains (38.1%) were detected as clarithromycin resistant (>0.5 mg l ). The new A2115G (n:6, 25%), A2144T (n:7, 29.1%) and G2141A, 8 (n:8, 33.3%) mutations and the classical A2142G (n:8, 33.3%) and A2143G (n:11, 45.8%) point mutations were detected in the 24 clarithromycin-resistant strains. The A2144T point mutation had the highest median MIC value (3 mg l ) amongst the new mutations, but the classical mutations (A2142G and A2143G) had the highest median MIC values (256 mg l ) overall. The presence of the A2115G (OR:31.66), A2144T (OR:36.92) or G2141A (OR:28.16) mutations increased the likelihood of clarithromycin resistance in H. pylori strains by 31.66-, 36.92- and 28.16-fold (ORs), respectively, according to the binary logistic regression analysis.

CONCLUSION

We concluded that classical mutations of the 23 S rRNA gene resulted in higher clarithromycin MIC values than new mutations. These new point mutations caused moderate elevations in the MIC values of clarithromycin-resistant H. pylori strains.

摘要

目的

我们旨在研究 23S rRNA 基因中最近发现的三个点突变(A2115G、G2141A 和 A2144T)的存在,并将其与土耳其幽门螺杆菌菌株中最常见的三个点突变(A2142G、A2142C 和 A2143G)进行比较。

方法

共纳入 63 例患者(平均年龄 47.08±12.27 岁)。采用 E 试验法(克拉霉素)对分离的幽门螺杆菌菌株进行克拉霉素抗菌药敏试验。采用实时 PCR 检测点突变。

结果

63 株幽门螺杆菌菌株中,共有 24 株(38.1%)被检测为克拉霉素耐药(>0.5mg/ml)。在 24 株克拉霉素耐药菌株中,检测到新的 A2115G(n:6,25%)、A2144T(n:7,29.1%)和 G2141A(n:8,33.3%)突变以及经典的 A2142G(n:8,33.3%)和 A2143G(n:11,45.8%)点突变。新突变中 A2144T 点突变的中位 MIC 值最高(3mg/ml),但经典突变(A2142G 和 A2143G)的中位 MIC 值总体最高(256mg/ml)。二元逻辑回归分析显示,A2115G(OR:31.66)、A2144T(OR:36.92)或 G2141A(OR:28.16)突变的存在使幽门螺杆菌菌株对克拉霉素耐药的可能性分别增加 31.66 倍、36.92 倍和 28.16 倍。

结论

我们得出结论,23S rRNA 基因的经典突变导致克拉霉素 MIC 值升高,而新突变导致克拉霉素耐药的幽门螺杆菌菌株 MIC 值中度升高。

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