Alfizah Hanafiah, Norazah Ahmad, Hamizah Razlan, Ramelah Mohamed
Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia.
Bacteriology Unit, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia.
J Med Microbiol. 2014 May;63(Pt 5):703-709. doi: 10.1099/jmm.0.069781-0.
Antibiotic resistance is increasing worldwide, and it has been regarded as the main factor reducing the efficacy of Helicobacter pylori therapy. The aim of this study was to determine the phenotype and genotype of antibiotic-resistant strains of H. pylori in the Malaysian population and to evaluate the impact of antibiotic resistance to eradication outcome. One hundred and sixty-one H. pylori isolates were analysed in this study. Metronidazole, clarithromycin, fluoroquinolone, amoxicillin and tetracycline susceptibilities were determined by Etest. PCR followed by DNA sequencing was carried out to determine mutations. The medical records of the patients infected with resistant strains were reviewed to determine the eradication outcome. Metronidazole resistance was encountered in 36.6 % of H. pylori isolates, whereas clarithromycin and fluoroquinolone resistance was observed in 1.2 and 1.9 % of isolates, respectively. All strains tested were susceptible to amoxicillin and tetracycline. Frameshift and nonsense mutations in rdxA and frxA genes resulting in stop codons contributed to metronidazole resistance, which leads to reduced eradication efficacy. A2142G and A2143G mutations of 23S rRNA were identified as causing failure of the eradication therapy. Mutation at either codon 87 or 91 of the gyrA gene was identified in fluoroquinolone-resistant strains. However, the effect of resistance could not be assessed. This study showed that frameshift and nonsense mutations in rdxA or frxA genes and point mutations in the 23S rRNA affected the efficacy of H. pylori eradication therapy.
抗生素耐药性在全球范围内不断增加,并且它已被视为降低幽门螺杆菌治疗疗效的主要因素。本研究的目的是确定马来西亚人群中幽门螺杆菌抗生素耐药菌株的表型和基因型,并评估抗生素耐药性对根除结果的影响。本研究分析了161株幽门螺杆菌分离株。通过Etest测定甲硝唑、克拉霉素、氟喹诺酮、阿莫西林和四环素的敏感性。进行聚合酶链反应(PCR)后测序以确定突变情况。对感染耐药菌株患者的病历进行回顾以确定根除结果。36.6%的幽门螺杆菌分离株对甲硝唑耐药,而分别有1.2%和1.9%的分离株对克拉霉素和氟喹诺酮耐药。所有测试菌株对阿莫西林和四环素敏感。rdxA和frxA基因中的移码突变和无义突变导致终止密码子,这导致了甲硝唑耐药,进而导致根除疗效降低。23S rRNA的A2142G和A2143G突变被确定为导致根除治疗失败。在氟喹诺酮耐药菌株中鉴定出gyrA基因第87或91密码子处的突变。然而,耐药的影响无法评估。本研究表明,rdxA或frxA基因中的移码突变和无义突变以及23S rRNA中的点突变影响了幽门螺杆菌根除治疗的疗效。