Susceptibility-guided bismuth quadruple therapies for resistant Helicobacter pylori infections

Tiankuo Yang; Renwei Hu; Xiaoqiong Tang; Yalin Shen; Alfred Tay; Xuenan Pi; Gang Wang; Aleksandra W Debowski; Keith A Stubbs; Mohammed Benghezal; Barry J Marshall; Hong Li; Hong Tang

doi:10.1093/pcmedi/pbaa010

Susceptibility-guided bismuth quadruple therapies for resistant Helicobacter pylori infections

Precis Clin Med. 2020 Jun;3(2):127-135. doi: 10.1093/pcmedi/pbaa010. Epub 2020 Mar 17.

Authors

Affiliations

¹ 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.
² Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China.
³ Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands 6009, Australia.
⁴ Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, West China Hospital, Chengdu 610041, China.
⁵ School of Molecular Sciences, University of Western Australia, Nedlands 6009, Australia.

Abstract

Increasing Helicobacter pylori 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 H. pylori 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). H. pylori 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 H. pylori 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 gyrA 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.

Keywords: Helicobacter pylori; antibiotic resistance; antimicrobial susceptibility testing; rescue therapy; whole-genome sequencing.