Insights into Helicobacter pylori macrolide resistance: a comprehensive systematic review and meta-analysis

Abstract

Background: Helicobacter pylori infection is a primary global health concern. However, the widespread use of antibiotics, particularly macrolides such as clarithromycin, has increased resistance among H. pylori strains. This study aimed to investigate the prevalence of macrolide resistance in H. pylori in different world regions.

Methods: This systematic literature search was performed using the appropriate search syntax after searching PubMed, Embase, Web of Science, and Scopus databases between May 2015 and December 2023. Statistical analysis was performed using Pooled and random effects model in R and the metafor package.

Results: A total of 7,768 articles were retrieved. After a thorough evaluation, 155 studies (by 178 reports) were finally eligible for inclusion in this systematic review and meta-analysis. According to the results, the majority of studies (178 reports from 43 countries) assessed clarithromycin susceptibility, with a pooled prevalence of 33.3% and high heterogeneity between studies (I ² = 98.57%, p < 0.001). The rate of erythromycin resistance was moderate (22.8%, 10 reports), while azithromycin resistance was 34.4% (4 reports). Subgroup analysis revealed significant differences in the prevalence of resistance based on geographic location, continent, and year of publication. Clarithromycin resistance increased from 29.1% (2015-2019) to 36.5% (2020-2023).

Conclusion: This study highlights the critical challenges of macrolide resistance in treating H. pylori infection. The high prevalence and geographic variation underscore the need for tailored treatment strategies based on regional resistance patterns. Furthermore, continuously monitoring resistance trends and investigating contributing factors are essential to optimize treatment.

Systematic review registration: https://www.crd.york.ac.uk/prospero; CRD42024557749.

Keywords: Helicobacter pylori; antibiotic resistance; azithromycin; clarithromycin; erythromycin; macrolides.

Figure 1

PRISMA flow chart summarizes the article selection procedure. Flow diagram illustrating the article selection process, including the identification, screening, eligibility, and inclusion of studies.

Figure 2

Forest plot illustrating the overall proportion of antibiotic resistant H. pylori isolates (Erythromycin, Clarithromycin, Azithromycin) estimated using a random-effects model.

Figure 3

Global prevalence of Erythromycin and Clarithromycin resistance in H. pylori. Clarithromycin resistance was lowest in Venezuela (1%) and highest in Australia (81.9%). Erythromycin resistance was absent in China, whereas Cameroon reported the highest rate (47.9%). CAN, Canada; USA, United States; MEX, Mexico; COL, Columbia; VEN, Venezuela; CHL, Chili; DEO, Denmark; BEL, Belgium; CHE, Switzerland; PRT, Portugal; ESP, Spain; POL, Poland; ITA, Italy; SVN, Slovenia; BGR, Bulgaria; ROU, Romania; RUS, Russia; TUN, Tunisia; DZA, Algeria; EGY, Egypt; CMR, Cameroon; ISR, Israel; JOR, Jordan; SAU, Saudia; IRN, Iran; TUR, Turkey; PAK, Pakistan; IND, India; CHN, China; BTN, Kingdom of Bhutan; BGD, Bangladesh; THA, Thailand; MYS, Malaysia; SGP, Singapore; COR, South Korea; JPN, Japan; TWN, Tiwan; VNM, Vietnam; KHN, Cambodia; IDN, Indonesia; AUS, Australia.

Figure 4

Global prevalence of macrolide-resistant Helicobacter pylori strains, categorized by resistance to clarithromycin and erythromycin across different regions.

Figure 5

The subgroup analysis results of clarithromycin-resistant H. pylori isolates are presented as follows: (A) Comparison of prevalence by continent, with Oceania having the highest resistance rate (81.9%) and the Americas having the lowest (27.1%). (B) Comparison of prevalence by AST shows no statistically significant difference in resistance prevalence across the different AST methods. (C) A comparison of the AST guidelines revealed no significant difference in the prevalence of resistance among the various guidelines. (D) Comparison by risk of bias using the JBI tool indicated no statistically significant difference in resistance prevalence among the quality groups. (E) Comparison of erythromycin resistance before and after 2020 showed a significant difference, with the 2015–2019 cohort having the lowest clarithromycin resistance rate (29.1%) and the 2020–2023 cohort showing the highest rate (36.5%).

Figure 6

Meta-regression analysis of macrolide resistance in H. pylori isolates from 2015 to 2023. (A) Scatter plot illustrating the trend of erythromycin-resistant isolates, showing a stable resistance rate with a correlation coefficient of −0.0194 and a non-significant p-value of 0.885. (B) The scatter plot showed a significant upward trend in clarithromycin resistance, with a positive correlation coefficient of 0.056 and a p-value of less than 0.001.