药物敏感性及CYP2C19基因检测对难治性儿童幽门螺杆菌感染根除率的影响

Effectiveness of eradication regimen based on the bacterial susceptibility and CYP2C19 genotype in children with refractory Helicobacter pylori infection

目的探讨对幽门螺杆菌(Hp)经验性根除方案效果欠佳患儿进行Hp培养+药敏试验以及CYP2C19基因检测的意义。方法前瞻性观察性队列研究。选择2017年12月至2018年5月在保定市儿童医院经阿莫西林+克拉霉素+奥美拉唑治疗失败的156例Hp感染患儿为研究对象,其中92例进行了Hp培养及基因检测。根据培养结果分为三组:(1)92例中75例培养成功,为培养成功组,根据药敏及CYP2C19基因结果个体化治疗;(2)92例中的17例培养失败,为培养失败组,根据CYP2C19基因结果治疗;(3)64例未进行Hp培养及CYP2C19基因检测的患儿为经验治疗组,经验性给予阿莫西林+甲硝唑+奥美拉唑+铋剂四联治疗。对患儿的耐药情况、CYP2C19基因多态性以及三组的治疗效果进行分析。组间比较采用χ^2检验。结果Hp培养+药敏结果:75例培养成功的患儿中,72例(96%)克拉霉素耐药,3例(4%)甲硝唑耐药,5例(7%)左氧氟沙星耐药,5例(7%)利福平耐药,1例(1%)四环素耐药,阿莫西林、呋喃唑酮无耐药。92例进行CYP2C19基因检测的患儿中强代谢型43例(47%),弱代谢型9例(10%),中间代谢型40例(43%)。培养成功组根除率为99%(74/75);培养失败组根除率为88%(15/17);经验治疗组根除率为72%(46/64)。培养成功组患儿的治疗成功率高于培养失败组和经验治疗组(χ^2=21.325,P<0.05);培养成功组患儿治疗成功率高于经验治疗组(χ^2=21.005,P<0.05);而培养失败组与经验治疗组差异无统计学意义(χ^2=1.154,P=0.283)。结论对于根除效果不理想的Hp感染患儿应进行Hp培养+药敏试验以及CYP2C19基因检测以指导治疗。

Objective To evaluate the effectiveness of eradication therapy based on Helicobacter pylori(Hp)susceptibility and CYP2C19 genotype in children with refractory Hp infection.Methods In this prospective observational cohort study,156 children with Hp refractory to amoxicillin+clarithromycin+omeprazole triple regimen in Baoding Children's Hospital from December 2017 to May 2018 were enrolled.Ninety-two of them underwent Hp culture and CYP2C19 detection.Seventy-five cases with positive Hp culture were defined as culture successful group and were treated according to Hp susceptibility and CYP2C19 genotype.Seventeen cases with negative Hp culture were defined as culture failed group and were treated only based on the results of CYP2C19 genotype.Sixty-four children who did not have Hp culture and CYP2C19 gene testing were defined as the empirical eradication therapy group and were treated with quadruple regimen(amoxicillin+metronidazole+omeprazole+bismuth).Bacterial resistance,CYP2C19 polymorphism and therapeutic effectiveness between the three groups were compared using chi-square test.Results Among the 75 positive Hp culture results,72(96%)were resistant to clarithromycin,3(4%)were resistant to metronidazole,5(7%)were resistant to levofloxacin,5(7%)were resistant to rifampicin,1(1%)was resistant to tetracycline,and none was resistant to amoxicillin and furazolidone.The CYP2C19 polymorphism in 92 patients showed that 43(47%)were extensive metabolizer(EM),9(10%)were poor metabolizer(PM),and 40(43%)were intermediate metabolizer(IM).In terms of the effectiveness,eradication rate in the culture successful group,culture failed group and empirical eradication therapy group were 99%(74/75),88%(15/17)and 72%(46/64),respectively(χ^2=21.325,P<0.05).The eradication rate in the culture successful group was significantly higher than that in empirical eradication therapy group(χ^2=21.005,P<0.05),while there was no difference between empirical eradication therapy group and culture failed group(χ^2=1.154,P=0.283).Conclusion Eradication regimen based on bacterial susceptibility and CYP2C19 genotype should be considered in children with refractory Hp infection.