Miftahussurur Muhammad, Cruz Modesto, Subsomwong Phawinee, Jiménez Abreu José A, Hosking Celso, Nagashima Hiroyuki, Akada Junko, Yamaoka Yoshio
Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.
Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas.
Am J Trop Med Hyg. 2017 May;96(5):1050-1059. doi: 10.4269/ajtmh.16-0729. Epub 2017 Feb 13.
Abstract antibiotic susceptibility in the Dominican Republic has not been monitored. We assessed antibiotic susceptibility in the Dominican Republic, and analyzed mutations associated with antibiotic resistance. We recruited 158 dyspeptic patients in Santo Domingo and used agar dilution to test susceptibility to five antibiotics. Polymerase chain reaction-based sequencing was used to assess , , , , and 23S rRNA mutations; next-generation sequencing was used to identify other metronidazole resistance-associated genes. Among 64 strains isolated, we identified two (3.1%), one (1.6%), and no strains with clarithromycin, amoxicillin, and tetracycline resistance, respectively. Moreover, high frequency of metronidazole resistance (53/64, 82.8%) was observed, whereas levofloxacin resistance is emerging (23/64, 35.9%). We identified many and mutations in metronidazole-resistant strains, but no synergistic effect was apparent. We revealed novel mutations in , , , and , irrespective of and mutations. Novel mutations at Ser-14 of and Arg-221 of were associated with different levels of metronidazole resistance. Most levofloxacin-resistant strains had a substitution at Asn-87 of , including the strain with the highest levofloxacin resistance, whereas only three substitutions were found at Ser-479 of with no synergistic effect. Besides the 23S rRNA A2142G mutation, we observed another mutation at T1958G in both clarithromycin-resistant strains. We confirmed high metronidazole and levofloxacin resistance associated with genetic mutations in the Dominican Republic. However, prevalence of clarithromycin resistance was low, suggesting that standard clarithromycin-based triple therapy remains useful as initial treatment of infection.
多米尼加共和国尚未对抗生素敏感性进行监测。我们评估了多米尼加共和国的抗生素敏感性,并分析了与抗生素耐药性相关的突变。我们在圣多明各招募了158名消化不良患者,采用琼脂稀释法检测对五种抗生素的敏感性。基于聚合酶链反应的测序用于评估、、、和23S rRNA突变;下一代测序用于鉴定其他与甲硝唑耐药相关的基因。在分离出的64株菌株中,我们分别鉴定出两株(3.1%)、一株(1.6%)对克拉霉素、阿莫西林耐药的菌株,未发现对四环素耐药的菌株。此外,观察到甲硝唑耐药的高频现象(53/64,82.8%),而左氧氟沙星耐药现象正在出现(23/64,35.9%)。我们在甲硝唑耐药菌株中鉴定出许多和突变,但未发现明显的协同效应。我们揭示了、、、和中的新突变,与和突变无关。和的Ser-14和Arg-221处的新突变与不同水平的甲硝唑耐药相关。大多数左氧氟沙星耐药菌株在的Asn-87处有一个替换,包括左氧氟沙星耐药性最高的菌株,而在的Ser-479处仅发现三个替换,且无协同效应。除了23S rRNA A2142G突变外,我们在两株克拉霉素耐药菌株中均观察到T1958G处的另一个突变。我们证实在多米尼加共和国,甲硝唑和左氧氟沙星耐药与基因突变相关。然而,克拉霉素耐药的患病率较低,这表明基于克拉霉素的标准三联疗法作为感染的初始治疗仍然有用。