巴西幽门螺杆菌对克拉霉素和氟喹诺酮类药物耐药性的检测：一项全国性调查。
Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil: A national survey.
作者信息
Sanches Bruno Squarcio, Martins Gustavo Miranda, Lima Karine, Cota Bianca, Moretzsohn Luciana Dias, Ribeiro Laercio Tenorio, Breyer Helenice P, Maguilnik Ismael, Maia Aline Bessa, Rezende-Filho Joffre, Meira Ana Carolina, Pinto Henrique, Alves Edson, Mascarenhas Ramiro, Passos Raissa, de Souza Julia Duarte, Trindade Osmar Reni, Coelho Luiz Gonzaga
机构信息
Bruno Squarcio Sanches, Gustavo Miranda Martins, Karine Lima, Bianca Cota, Luciana Dias Moretzsohn, Ana Carolina Meira, Henrique Pinto, Edson Alves, Raissa Passos, Julia Duarte de Souza, Osmar Reni Trindade, Luiz Gonzaga Coelho, Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 30130-100, Brazil.
出版信息
World J Gastroenterol. 2016 Sep 7;22(33):7587-94. doi: 10.3748/wjg.v22.i33.7587.
AIM
To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods.
METHODS
The primary antibiotic resistance rates of Helicobacter pylori (H. pylori) were determined from November 2012 to March 2015 in the Southern, South-Eastern, Northern, North-Eastern, and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female, mean age 43 years (range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using GenoType HelicoDR (Hain Life Science, Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies, multiplex amplification, and reverse hybridization.
RESULTS
Clarithromycin resistance was found in 83 (16.9%) patients, and fluoroquinolone resistance was found in 66 (13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones (P = 0.55 and P = 0.06, respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3% (21/490) of patients. The A2147G mutation was present in 90.4% (75/83), A2146G in 16.9% (14/83) and A2146C in 3.6% (3/83) of clarithromycin-resistant patients. In 10.8% (9/83) of clarithromycin-resistant samples, more than 01 mutation in the 23S rRNA gene was noticed. In fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. D91N mutation was observed in 34.8% (23/66), D91G in 18.1% (12/66), N87K in 16.6% (11/66) and D91Y in 13.6% (9/66) of cases. Among fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test.
CONCLUSION
The H. pylori clarithromycin resistance rate in Brazil is at the borderline (15%-20%) for applying the standard triple therapy. The fluoroquinolone resistance rate (13.5%) is equally concerning.
目的
采用分子方法评估巴西幽门螺杆菌对克拉霉素和氟喹诺酮类药物的耐药性。
方法
2012年11月至2015年3月期间，在巴西的南部、东南部、北部、东北部和中西部地区测定幽门螺杆菌（H. pylori）的主要抗生素耐药率。纳入490例此前从未接受过该感染治疗的幽门螺杆菌患者[女性占66%，平均年龄43岁（范围：18 - 79岁）]。所有患者均接受了胃窦和胃体活检的胃镜检查，并使用GenoType HelicoDR（德国海因生命科学公司）进行分子检测。该检测用于检测幽门螺杆菌的存在，并鉴定负责克拉霉素和氟喹诺酮耐药性的基因中的点突变。分子检测过程分为三个步骤：从活检组织中提取DNA、多重扩增和反向杂交。
结果
83例（16.9%）患者存在克拉霉素耐药，66例（13.5%）患者存在氟喹诺酮耐药。巴西不同地区对克拉霉素或氟喹诺酮的耐药性无统计学差异（分别为P = 0.55和P = 0.06）。4.3%（21/490）的患者对克拉霉素和氟喹诺酮双重耐药。克拉霉素耐药患者中，90.4%（75/83）存在A2147G突变，16.9%（14/83）存在A2146G突变，3.6%（3/83）存在A2146C突变。在10.8%（9/83）的克拉霉素耐药样本中，23S rRNA基因中发现了不止1个突变。在氟喹诺酮耐药样本中，37.9%（25/66）显示出GenoType HelicoDR检测未指定的突变。34.8%（23/66）的病例中观察到D91N突变，18.1%（12/66）观察到D91G突变，16.6%（11/66）观察到N87K突变，13.6%（9/66）观察到D91Y突变。在氟喹诺酮耐药样本中，37.9%（25/66）显示出GenoType HelicoDR检测未指定的突变。
结论
巴西幽门螺杆菌对克拉霉素的耐药率处于应用标准三联疗法的临界值（15% - 20%）。氟喹诺酮耐药率（13.5%）同样令人担忧。
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