Antibiotic resistance of Helicobacter pylori isolated from patients in Nanjing, China: A cross-section study from 2018 to 2021

Zongdan Jiang, Xuetian Qian, Zhi Wang, Yunfan Dong, Yuqin Pan, Zhenyu Zhang, Shukui Wang, Zongdan Jiang, Xuetian Qian, Zhi Wang, Yunfan Dong, Yuqin Pan, Zhenyu Zhang, Shukui Wang

Abstract

The increasing antibiotic resistance of Helicobacter pylori infection is a globally urging problem. To investigate the H. pylori resistance situation in Nanjing, China, we enrolled patients in Nanjing First Hospital from January 2018 to May 2021. H. pylori strains were isolated from patients who had at least one positive 13C-urea breath or rapid urease result. Subsequently, we performed antibiotic susceptibility tests on the isolated strains to clarithromycin, metronidazole, levofloxacin, amoxicillin, furazolidone and tetracycline. ARMS-PCR was conducted to determine H. pylori clarithromycin resistance gene mutation. Our results demonstrated that the primary resistance rates of metronidazole, clarithromycin, levofloxacin, amoxicillin, furazolidone and tetracycline were 67.19% (1417/2109), 35.99% (759/2109), 24.23% (511/2109), 0.76% (16/2109), 0.28% (6/2109) and 0.09% (2/2109), respectively. The resistance rates of metronidazole, clarithromycin and levofloxacin elevated significantly after treatment and the three antibiotics composed the majority of multi-resistance patterns. However, the resistance rates of amoxicillin, furazolidone and tetracycline were still in low levels after treatment. ARMS-PCR showed a rather good consistency with antibiotic susceptibility test in detecting clarithromycin resistance, with a kappa value of 0.79. Overall, this study revealed the latest complex situation of antibiotic resistance of H. pylori infection in Nanjing and offered suggestions on clinical medication for curing H. pylori.

Keywords: ARMS-PCR; Helicobacter pylori; Nanjing; antibiotic resistance; clarithromycin.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Jiang, Qian, Wang, Dong, Pan, Zhang and Wang.

Figures

Figure 1
Figure 1
Flowchart depicting the study design. * RUT, rapid urease test.
Figure 2
Figure 2
Multi-antibiotics resistance patterns of H pylori. (A, B) Dual-antibiotics resistance patterns. (A) Composition of antibiotics resistance patterns. The green part represented the proportion of total dual-antibiotics resistance patterns, accounting for 24.46% (678/2772). (B) Composition of dual-antibiotics resistance patterns. (C, D) Triple-antibiotics resistance patterns. (C) Composition of antibiotics resistance patterns. The purple part represented the proportion of total triple-antibiotics resistance patterns, accounting for 20.82% (577/2772). (D) Composition of triple-antibiotics resistance patterns. (E, F) Quadruple-antibiotics resistance patterns. (E) Composition of antibiotics resistance patterns. The orange part represented the proportion of total quadruple-antibiotics resistance patterns, accounting for 0.25% (7/2772). (F) Composition of quadruple-antibiotics resistance patterns. AMX, amoxicillin; CLA, clarithromycin; FZD, furazolidone; MTZ, metronidazole; LEV, levofloxacin; TET, tetracycline.

References

    1. Alarcon T., Urruzuno P., Martinez M. J., Domingo D., Llorca L., Correa A., et al. . (2017). Antimicrobial susceptibility of 6 antimicrobial agents in helicobacter pylori clinical isolates by using EUCAST breakpoints compared with previously used breakpoints. Enferm. Infecc. Microbiol. Clin. 35 (5), 278–282. doi: 10.1016/j.eimc.2016.02.010
    1. Alba C., Blanco A., Alarcon T. (2017). Antibiotic resistance in helicobacter pylori. Curr. Opin. Infect. Dis. 30 (5), 489–497. doi: 10.1097/QCO.0000000000000396
    1. Ang T. L., Fock K. M., Ang D., Kwek A. B., Teo E. K., Dhamodaran S. (2016). The changing profile of helicobacter pylori antibiotic resistance in Singapore: A 15-year study. Helicobacter 21 (4), 261–265. doi: 10.1111/hel.12291
    1. Dolan B., Burkitt-Gray L., Shovelin S., Bourke B., Drumm B., Rowland M., et al. . (2018). The use of stool specimens reveals helicobacter pylori strain diversity in a cohort of adolescents and their family members in a developed country. Int. J. Med. Microbiol. 308 (2), 247–255. doi: 10.1016/j.ijmm.2017.11.005
    1. Gao C. P., Zhang D., Zhang T., Wang J. X., Han S. X., Graham D. Y., et al. . (2020). PPI-amoxicillin dual therapy for helicobacter pylori infection: An update based on a systematic review and meta-analysis. Helicobacter 25 (4), e12692. doi: 10.1111/hel.12692
    1. Gong Y., Yuan Y. (2018). Resistance mechanisms of helicobacter pylori and its dual target precise therapy. Crit. Rev. Microbiol. 44 (3), 371–392. doi: 10.1080/1040841X.2017.1418285
    1. Goudarzi M., Heidary M., Azad M., Fazeli M., Goudarzi H. (2016). Evaluation of antimicrobial susceptibility and integron carriage in helicobacter pylori isolates from patients. Gastroenterol. Hepatol. Bed. Bench. 9 (Suppl1), S47–S52. doi: 10.22037/ GHFBB.V0I0.981
    1. Gunnarsdottir A. I., Gudjonsson H., Hardardottir H., Jonsdottir K. D., Bjornsson E. S. (2017). Antibiotic susceptibility of helicobacter pylori in Iceland. Infect. Dis. (Lond). 49 (9), 647–654. doi: 10.1080/23744235.2017.1317359
    1. Hooi J. K. Y., Lai W. Y., Ng W. K., Suen M. M. Y., Underwood F. E., Tanyingoh D., et al. . (2017). Global prevalence of helicobacter pylori infection: Systematic review and meta-analysis. Gastroenterology 153 (2), 420–429. doi: 10.1053/j.gastro.2017.04.022
    1. Hu Y., Zhu Y., Lu N. H. (2017). Primary antibiotic resistance of helicobacter pylori in China. Dig. Dis. Sci. 62 (5), 1146–1154. doi: 10.1007/s10620-017-4536-8
    1. Jiang Z. D., He B. S., Zhang Z. Y., Wang S. K., Ran D., Wang Z. B. (2021). Analysis of the primary and post-treatment antibiotic resistance of helicobacter pylori in the nanjing area. Curr. Pharm. Biotechnol. 22 (5), 682–685. doi: 10.2174/1389201021666200722162613
    1. Karpinski T. M., Andrzejewska E., Eder P., Linke K., Szkaradkiewicz A. (2015). Evaluation of antimicrobial resistance of helicobacter pylori in the last 15 years in West Poland. Acta Microbiol. Immunol. Hung. 62 (3), 287–293. doi: 10.1556/030.62.2015.3.6
    1. Liu W. Z., Xie Y., Lu H., Cheng H., Zeng Z. R., Zhou L. Y., et al. . (2018). Fifth Chinese national consensus report on the management of helicobacter pylori infection. Helicobacter 23 (2), e12475. doi: 10.1111/hel.12475
    1. Malfertheiner P., Megraud F., O’Morain C. A., Gisbert J. P., Kuipers E. J., Axon A. T., et al. . (2017). Management of helicobacter pylori infection-the maastricht V/Florence consensus report. Gut 66 (1), 6–30. doi: 10.1136/gutjnl-2016-312288
    1. Megraud F., Lehn N., Lind T., Bayerdorffer E., O’Morain C., Spiller R., et al. . (1999). Antimicrobial susceptibility testing of helicobacter pylori in a large multicenter trial: the MACH 2 study. Antimicrob. Agents Chemother. 43 (11), 2747–2752. doi: 10.1128/AAC.43.11.2747
    1. Megraud F., Lehours P. (2007). Helicobacter pylori detection and antimicrobial susceptibility testing. Clin. Microbiol. Rev. 20 (2), 280–322. doi: 10.1128/CMR.00033-06
    1. Miehlke S., Hansky K., Schneider-Brachert W., Kirsch C., Morgner A., Madisch A., et al. . (2006). Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of helicobacter pylori resistant to both metronidazole and clarithromycin. Aliment. Pharmacol. Ther. 24 (2), 395–403. doi: 10.1111/j.1365-2036.2006.02993.x
    1. NIH Consensus Conference (1994). Helicobacter pylori in peptic ulcer disease. NIH consensus development panel on helicobacter pylori in peptic ulcer disease. JAMA 272 (1), 65–69. doi: 10.1001/ jama.1994.03520010077036
    1. Occhialini A., Urdaci M., Doucet-Populaire F., Bebear C. M., Lamouliatte H., Megraud F. (1997). Macrolide resistance in helicobacter pylori: rapid detection of point mutations and assays of macrolide binding to ribosomes. Antimicrob. Agents Chemother. 41 (12), 2724–2728. doi: 10.1128/AAC.41.12.2724
    1. Sanchez A. R., Rogers R. S., 3rd, Sheridan P. J. (2004). Tetracycline and other tetracycline-derivative staining of the teeth and oral cavity. Int. J. Dermatol. 43 (10), 709–715. doi: 10.1111/j.1365-4632.2004.02108.x
    1. Sapmaz F., Kalkan I. H., Atasoy P., Basyigit S., Guliter S. (2017). A non-inferiority study: Modified dual therapy consisting higher doses of rabeprazole is as successful as standard quadruple therapy in eradication of helicobacter pylori. Am. J. Ther. 24 (4), e393–e398. doi: 10.1097/MJT.0000000000000316
    1. Song Z., Zhang J., He L., Chen M., Hou X., Li Z., et al. . (2014). Prospective multi-region study on primary antibiotic resistance of helicobacter pylori strains isolated from Chinese patients. Dig. Liver. Dis. 46 (12), 1077–1081. doi: 10.1016/j.dld.2014.08.038
    1. Stone G. G., Shortridge D., Flamm R. K., Versalovic J., Beyer J., Idler K., et al. . (1996). Identification of a 23S rRNA gene mutation in clarithromycin-resistant helicobacter pylori. Helicobacter 1 (4), 227–228. doi: 10.1111/j.1523-5378.1996.tb00043.x
    1. Tai W. C., Liang C. M., Kuo C. M., Huang P. Y., Wu C. K., Yang S. C., et al. . (2019). A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy regimen achieves a high eradication rate as first-line anti-helicobacter pylori treatment in Taiwan: a prospective randomized trial. J. Antimicrob. Chemother. 74 (6), 1718–1724. doi: 10.1093/jac/dkz046
    1. Taylor D. E., Ge Z., Purych D., Lo T., Hiratsuka K. (1997). Cloning and sequence analysis of two copies of a 23S rRNA gene from helicobacter pylori and association of clarithromycin resistance with 23S rRNA mutations. Antimicrob. Agents Chemother. 41 (12), 2621–2628. doi: 10.1128/AAC.41.12.2621
    1. Tshibangu-Kabamba E., Yamaoka Y. (2021). Helicobacter pylori infection and antibiotic resistance - from biology to clinical implications. Nat. Rev. Gastroenterol. Hepatol. 18 (9), 613–629. doi: 10.1038/s41575-021-00449-x
    1. Vianna J. S., Ramis I. B., Ramos D. F., VON Groll A., Silva P. E. (2016). Drug resistance in helicobacter pylori. Arq. Gastroenterol. 53 (4), 215–223. doi: 10.1590/S0004-28032016000400002
    1. Xie C., Lu N. H. (2015). Review: clinical management of helicobacter pylori infection in China. Helicobacter 20 (1), 1–10. doi: 10.1111/hel.12178
    1. Yu L., Luo L., Long X., Liang X., Ji Y., Graham D. Y., et al. . (2019). High-dose PPI-amoxicillin dual therapy with or without bismuth for first-line helicobacter pylori therapy: A randomized trial. Helicobacter 24 (4), e12596. doi: 10.1111/hel.12596
    1. Zhang Y. X., Zhou L. Y., Song Z. Q., Zhang J. Z., He L. H., Ding Y. (2015). Primary antibiotic resistance of helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing: a prospective serial study. World J. Gastroenterol. 21 (9), 2786–2792. doi: 10.3748/wjg.v21.i9.2786
    1. Zhuge L., Wang Y., Wu S., Zhao R. L., Li Z., Xie Y. (2018). Furazolidone treatment for helicobacter pylori infection: A systematic review and meta-analysis. Helicobacter 23 (2), e12468. doi: 10.1111/hel.12468

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