Yang Tiankuo, Hu Renwei, Tang Xiaoqiong, Shen Yalin, Tay Alfred, Pi Xuenan, Wang Gang, Debowski Aleksandra W, Stubbs Keith A, Benghezal Mohammed, Marshall Barry J, Li Hong, Tang Hong
West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China.
Precis Clin Med. 2020 Jun;3(2):127-135. doi: 10.1093/pcmedi/pbaa010. Epub 2020 Mar 17.
Increasing resistance to antibiotics has ledthat molecular testing is appropriate as a sub to adoption of seven different bismuth quadruple therapies (BQT) in China without differentiation of first-line or second-line regimens. The objective of this study was to evaluate the efficacy of susceptibility-guided BQT for patients who had experienced previous treatment failures. A total of 133 patients was included and was successfully cultured from 101 patients (75.9%) for subsequent antimicrobial susceptibility testing (AST). Based on the AST results, 88 patients completed one of five AST-guided 14-day BQT regimens: esomeprazole and bismuth colloidal pectin, along with either, amoxicillin and clarithromycin (EBAC), amoxicillin and levofloxacin (EBAL), amoxicillin and furazolidone (EBAF), amoxicillin and tetracycline (EBAT), or tetracycline and furazolidone (EBTF). eradication rates were 100% for EBAC (5/5), EBAL (13/13), EBAF (14/14), and EBTF (43/43), but 76.9% for EBAT (10/13). The three patients that failed the EBAT regimen were all cured after subsequent treatment with the EBTF regimen. Our study demonstrates the excellent efficacy of the AST-guided BQT for referred patients, and that the current EBAT regimen, used in clinics, needs to be optimized. In addition, 57 of the isolates were subjected to whole-genome sequencing. Analysis of the sequences revealed that point mutations in 23S rRNA correlated well with the phenotypic clarithromycin resistance with a concordance of 91.2%, while the concordance between phenotypic levofloxacin resistance and point mutations was 82.3%. This suggests that molecular testing is appropriate as a substitute for AST as a more rapid and cost-effective method for determining clarithromycin and levofloxacin resistance in Chinese patients.
抗生素耐药性的增加导致在中国不加区分一线或二线治疗方案就采用七种不同的铋四联疗法(BQT)。本研究的目的是评估药敏指导下的BQT对既往治疗失败患者的疗效。共纳入133例患者,其中101例(75.9%)成功培养出细菌用于后续的抗菌药物敏感性试验(AST)。根据AST结果,88例患者完成了五种AST指导的14天BQT方案之一:埃索美拉唑和果胶铋,联合阿莫西林和克拉霉素(EBAC)、阿莫西林和左氧氟沙星(EBAL)、阿莫西林和呋喃唑酮(EBAF)、阿莫西林和四环素(EBAT)或四环素和呋喃唑酮(EBTF)。EBAC(5/5)、EBAL(13/13)、EBAF(14/14)和EBTF(43/43)的根除率为100%,但EBAT(10/13)为76.9%。EBAT方案治疗失败的3例患者在随后接受EBTF方案治疗后均治愈。我们的研究证明了AST指导的BQT对转诊患者具有优异的疗效,并且目前临床使用的EBAT方案需要优化。此外,对57株分离株进行了全基因组测序。序列分析显示,23S rRNA中的点突变与克拉霉素表型耐药性相关性良好,一致性为91.2%,而左氧氟沙星表型耐药性与点突变之间的一致性为82.3%。这表明分子检测作为一种更快速且经济有效的方法,适合替代AST来确定中国患者的克拉霉素和左氧氟沙星耐药性。