Multicentre, cross-sectional surveillance of Helicobacter pylori prevalence and antibiotic resistance to clarithromycin and levofloxacin in urban China using the string test coupled with quantitative PCR
Authors: Liang Wang, Zhengkang Li, Chin Yen Tay, Barry J Marshall, Bing Gu, Yan Tian, Xubo Dai, Hong Du, Qiong Dai, Cui Feng, Qi Fang, Yanjiang Huang, Yizhong Hu, Min He, Guochu Hu, Hui Huang, Qixin Li, Mingbo Liu, Junhong Li, Jinhua Luo, Zhifang Lin, Fen Li, Haitao Liu, Dong Xia, Baohua Man, Jianhong Ma, Shifu Tang, Bofu Tang, Jiliang Wang, Tao Wu, Xiaoling Wang, Handong Wang, Shuchun Wang, Jing Xu, Jiancheng Xu, Qingquan Xie, Rongzhang Xie, Yunxian Ye, Gailing Yuan, Xingcheng Zhu, Shulei Zhao, Wenbi Zou, Liyan Zhang, Bin Zhou
Journal: The Lancet Microbe (2024)

Antibiotic-resistant Helicobacter pylori infections pose a considerable burden on health care in China.1Wang Y Du J Zhang D et al.Primary antibiotic resistance in Helicobacter pylori in China: a systematic review and meta-analysis.J Glob Antimicrob Resist. 2023; 34: 30-38Crossref PubMed Scopus (1) Google Scholar However, the existing knowledge of H pylori prevalence and antibiotic resistance in urban China is derived from heterogeneous testing methodologies and studied populations.2Ren S Cai P Liu Y et al.Prevalence of Helicobacter pylori infection in China: a systematic review and meta-analysis.J Gastroenterol Hepatol. 2022; 37: 464-470Crossref PubMed Scopus (82) Google Scholar The string test is a minimally invasive method used to obtain gastric fluid samples3Schneider RE Torres M Solis C Passarelli L Schneider FE Vettorazzi M A simple method to detect Helicobacter pylori in gastric specimens.BMJ. 1990; 300: 1559Crossref PubMed Google Scholar,4Samuels AL Windsor HM Ho GY Goodwin LD Marshall BJ Culture of Helicobacter pylori from a gastric string may be an alternative to endoscopic biopsy.J Clin Microbiol. 2000; 38: 2438-2439Crossref PubMed Google Scholar and can be used to detect H pylori infection and antibiotic resistance when combined with quantitative PCR (appendix p 3–4).5Han X Yu X Gao X et al.Quantitative PCR of string-test collected gastric material: a feasible approach to detect Helicobacter pylori and its resistance against clarithromycin and levofloxacin for susceptibility-guided therapy.Helicobacter. 2023; 28e12985Crossref Scopus (1) Google Scholar We conducted nationwide, multicentre, cross-sectional surveillance using this combined diagnostic approach to provide an overview of H pylori prevalence and antibiotic resistance rates, specifically against clarithromycin and levofloxacin, in urban China. The surveillance was conducted from March 1 to Nov 30, 2023, and included 52 municipal cities across 26 provinces. The study included a cohort of 12 902 individuals (4375 male and 8527 female) meeting predetermined inclusion and exclusion criteria (appendix p 5). Among all participants, 3494 (27·08%) individuals were positive for H pylori, with a higher positivity rate seen in men (1262 [28·85%] of 4375) than in women (2232 [26·18%] of 8527; p<0·001). Disparities in the prevalence of H pylori infection were also observed in different age groups, with the highest prevalence in those aged between 30 and 49 years (>27·08%, [1872 (28.98%) of 6459]), consistent with the results of two independent studies conducted previously.2Ren S Cai P Liu Y et al.Prevalence of Helicobacter pylori infection in China: a systematic review and meta-analysis.J Gastroenterol Hepatol. 2022; 37: 464-470Crossref PubMed Scopus (82) Google Scholar,6Zamani M Ebrahimtabar F Zamani V et al.Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection.Aliment Pharmacol Ther. 2018; 47: 868-876Crossref PubMed Scopus (467) Google Scholar Accordingly, we performed antibacterial testing utilising qPCR on individuals who were H pylori-positive using two antibiotics: clarithromycin and levofloxacin. 1776 (50·83%) individuals with infection showed resistance to clarithromycin, of whom 1202 (53·85%) were female and 574 (45·48%) were male. Within the age group of 40–60 years, the prevalence of clarithromycin resistance consistently exceeded 50·83% (1149 [54.58%] of 2105). Resistance to levofloxacin was seen in 1648 (47·17%) individuals, demonstrating a higher frequency among women (1094 [49·01%]) than among men (554 [43·90%]). Among the different age subgroups, levofloxacin resistance was consistently higher in individuals aged between 40 and 60 years (>47·17%, [1148 (54.54%) of 2105]). In the cohort of individuals aged 40–60 years, an increased resistance to clarithromycin and levofloxacin was evident, which might be related to increased antibiotic exposure with advancing age and increased susceptibility to respiratory and urinary tract infections. Likewise, the heightened prevalence of clarithromycin and levofloxacin resistance among women, as opposed to men, could be attributed to the frequent use of clarithromycin and levofloxacin for managing gynaecological infections.7Zhang YX Zhou LY Song ZQ Zhang JZ He LH Ding Y Primary antibiotic resistance of Helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing: a prospective serial study.World J Gastroenterol. 2015; 21: 2786-2792Crossref PubMed Scopus (111) Google Scholar,8Kocsmár É Buzás GM Szirtes I et al.Primary and secondary clarithromycin resistance in Helicobacter pylori and mathematical modeling of the role of macrolides.Nat Commun. 2021; 12: 2255Crossref PubMed Scopus (0) Google Scholar A comprehensive overview of the baseline characteristics of all study participants is provided in the appendix (p 6). H pylori prevalence shows significant variability between provinces, ranging from 15·03% in Hunan to 42·58% in Fujian (appendix p 3–4). These data underscore the correlation between geographical regions and infection rates, with southern provinces generally experiencing lower infection rates than their northern and eastern counterparts. In the context of antibiotic resistance, the prevalence of clarithromycin resistance has shown an increasing trend in the northern provinces, reaching 77·08% in Heilongjiang and 77·91% in Jilin. Conversely, resistance rates have gradually decreased in southern provinces, with Hunan registering the lowest resistance rate at 27·78%. Resistance to levofloxacin is higher in eastern coastal provinces and lower in southern provinces, indicating regional disparities in antibiotic resistance. Regarding the analysis of the seven geographical regions in China (appendix p 3–4), H. pylori infection was more prevalent in north and northwest China than in central China, consistent with the results of a recently conducted large-scale, family-based epidemiological study in China.9Zhou XZ Lyu NH Zhu HY et al.Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention.Gut. 2023; 72: 855-869Crossref PubMed Scopus (0) Google Scholar When exploring regional variations in drug resistance in China, northeast China stands out with the highest prevalence of clarithromycin resistance (75·28%). This figure significantly exceeds rates in north, northwest, and east China, although these regions also show clarithromycin resistance greater than 50·00%. Furthermore, in terms of levofloxacin resistance, northeast China again has the highest resistance rate of 57·30%, with the regions of northwest (51·52%) and east (50·10%) China following closely. Central China has the lowest levofloxacin resistance rate of 39·22% among the seven geographical regions of China, which emphasises regional differences in antibiotic resistance. This inter-regional disparity in H pylori infection and antibiotic resistance might be associated with regional differences in socioeconomic conditions, hygiene, availability of health-care facilities, and practices of antibiotic use. Our investigation reveals that the aggregate prevalence of H pylori among urban Chinese people is 27·08%, a notably lower figure than the previously approximated prevalence for the broader Chinese population (44·20%).2Ren S Cai P Liu Y et al.Prevalence of Helicobacter pylori infection in China: a systematic review and meta-analysis.J Gastroenterol Hepatol. 2022; 37: 464-470Crossref PubMed Scopus (82) Google Scholar The resistance rates to clarithromycin and levofloxacin were also unexpectedly high in the urban Chinese population, with an average resistance rate of 50·83% for clarithromycin and 47·17% for levofloxacin, highlighting the importance of controlling drug resistance to H pylori infection in urban China. Susceptibility-guided therapy should also be adopted in clinical practice to improve the successful eradication of H pylori infection. We declare no competing interests. LW and ZL are co-first authors. CYT, BJM, and BG are co-senior authors. This research was supported by the National Natural Science Foundation of China (82272423 and 82072380), National Key Research and Development Program of China (2023YFC2606200 and 2022YFC0870100), Research Foundation for Advanced Talents of Guangdong Provincial People's Hospital (KJ012021097 and KY012023293), Sanming Project of Medicine in Shenzhen (SZSM201510050), and Guangdong Basic and Applied Basic Research Foundation (2022A1515220023). Download .pdf (1.02 MB) Help with pdf files Supplementary appendix Download .pdf (.21 MB) Help with pdf files Supplementary methods