Abstract
The resistance of Helicobacter pylori (H. pylori) to antibiotics has been increasing worldwide and varies across different geographic areas and times. Limited studies reported the prevalence of antibiotic resistance and its related gene mutations in children in Chongqing, a city located in southwest China. We collected 112 H. pylori strains isolated from gastric biopsies of 156 children at Children’s Hospital of Chongqing Medical University and calculated resistance rates of these strains to six antibiotics. The A2143G and A2142G mutations in 23S rRNA gene, which are related to clarithromycin resistance, and Asn87 and Asp91 mutations in gyrA gene, which are related to levofloxacin resistance, were investigated in 102 strains. The resistance rates to clarithromycin, metronidazole, and levofloxacin were 47.3% (53/112), 88.4% (99/112), and 18.8% (21/112), respectively. No resistance to amoxicillin, tetracycline, and furazolidone was observed. Dual and triple resistance percentages were 37.5% (42/112) and 10.7% (12/112), respectively. The detection rate of A2143G mutation in 23S rRNA gene was 83.3% (40/48). The detection rates of mutations of Asn87 and Asp91 in gyrA gene were 52.6% (10/19) and 36.8% (7/19), respectively.
Conclusion: The prevalence of H. pylori resistance to clarithromycin, metronidazole, and levofloxacin was high in children in Chongqing, China. The A2143G mutation was detected in most clarithromycin-resistant strains, and Asn87 and Asp91 of gyrA mutation points were common in levofloxacin-resistant strains. In clinical practice, anti-H. pylori therapy should be individualized based on a susceptibility test.
What is Known: • The resistance of H. pylori to antibiotics changes with the geographic areas and that in Asia the resistance rate is high. • Mutation plays a vital role in antibiotics resistance of H. pylori. | |
What is New: • High resistance rates to single and multiple antibiotics in children of Chongqing, a city located in southwest China, were observed. • Molecular assays showed good conformance with susceptibility test results to direct antibiotic resistance of H. pylori. |
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The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.
Change history
21 October 2022
A Correction to this paper has been published: https://doi.org/10.1007/s00431-022-04670-x
Abbreviations
- AMO:
-
Amoxicillin
- CLA:
-
Clarithromycin
- FUR:
-
Furazolidone
- LEV:
-
Levofloxacin
- MTZ:
-
Metronidazole
- NUD:
-
Non-ulcer disease
- PUD:
-
Peptic ulcer diseases
- PPI:
-
Proton pump inhibitor
- TET:
-
Tetracycline
References
Malfertheiner P, Megraud F, O’Morain CA et al (2017) Management of Helicobacter pylori infection the Maastricht V/Florence Consensus Report. Gut 66:6–30. https://doi.org/10.1136/gutjnl-2016-312288
Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, Czinn S, Gold BD, Guarner J, Elitsur Y, Homan M, Kalach N, Kori M, Madrazo A, Megraud F, Papadopoulou A, Rowland M (2017) Joint ESPGHAN/NASPGHAN guidelines for the management of Helicobacter pylori in children and adolescents (update 2016). J Pediatr Gastroenterol Nutr 64:991–1003. https://doi.org/10.1097/MPG.0000000000001594
Lee YC, Chiang TH, Chou CK, Tu YK, Liao WC, Wu MS, Graham DY (2016) Association between Helicobacter pylori eradication and gastric cancer incidence: a systematic review and meta-analysis. Gastroenterology 150:1113–1124
Graham DY, Fischbach L (2010) Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 59:1143–1153. https://doi.org/10.1136/gut.2009.192757
Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E (2018) Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization regions. Gastroenterology 155:1372–1382. https://doi.org/10.1053/j.gastro.2018.07.007
Versalovic J, Shortridge D, Kibler K, Griffy MV, Beyer J, Flamm RK, Tanaka SK, Graham DY, Go MF (1996) Mutations in 23S rRNA are associated with clarithromycin resistance in Helicobacter pylori. Antimicrob Agents Ch 40:477–480. https://doi.org/10.1128/AAC.40.2.477
Hu Y, Zhang M, Lu B, Dai JF (2016) Helicobacter pylori and antibiotic resistance, a continuing and intractable problem. Helicobacter 21:349–363. https://doi.org/10.1111/hel.12299
Liu GD, Xu XW, He LH, Ding ZL, Gu YX, Zhang JZ, Zhou LY (2011) Primary antibiotic resistance of Helicobacter pylori isolated from Beijing children. Helicobacter 16:356–362. https://doi.org/10.1111/j.1523-5378.2011.00856.x
Li L, Ke YN, Yu CH, Li GG, Yang NM, Zhang JZ, Li YM (2017) Antibiotic resistance of Helicobacter pylori in Chinese children: a multicenter retrospective study over 7 years. Helicobacter 22:e12373. https://doi.org/10.1111/hel.12373
Shu XL, Yin GF, Liu MN, Peng KR, Zhao H, Jiang MZ (2018) Antibiotics resistance of Helicobacter pylori in children with upper gastrointestinal symptoms in Hangzhou. China Helicobacter 23:e12481. https://doi.org/10.1111/hel.12481
Li DD, Guan DX, Guo J, Fang YL, Guo S, He LH, Zhang JZ, Zhou LY, Yu FH, Zhou J, Wang GL, Zhang J, Xu XW (2019) Analysis of antibiotic resistance and influencing factors for Helicobacter pylori in children. Chin J Appl Clin Pediatr 34:1451–1453
Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility Testing (2009) Nineteenth Informational Supplement, M100-S19. Clinical and Laboratory Standards Institute. Wayne, PA: Document M100-S19
Osato MS, Reddy R, Reddy SG, Penland RL, Graham DY (2001) Comparison of the Etest and the NCCLS-approved agar dilution method to detect metronidazole and clarithromycin resistant Helicobacter pylori. Int J Antimicrob Ag 17:39–44. https://doi.org/10.1016/S0924-8579(00)00320-4
Seo JH, Jun JS, Yeom JS, Park JS, Youn HS, Ko GH, Baik SC, Lee WK, Cho MJ, Rhee KH (2013) Changing pattern of antibiotic resistance of Helicobacter pylori in children during 20 years in Jinju, South Korea. Pediatr Int 55:332–336. https://doi.org/10.1111/ped.12048
Kato S, Fujimura S (2010) Primary antimicrobial resistance of Helicobacter pylori in children during the past 9 years. Pediatr Int 52:187–190. https://doi.org/10.1111/j.1442-200X.2009.02915.x
Kalach N, Serhal L, Asmar E et al (2007) Helicobacter pylori primary resistant strains over 11 years in French children. Diagn Micr Infec Dis 59:217–222. https://doi.org/10.1016/j.diagmicrobio.2007.05.003
Regnath T, Raecke O, Enninger A, Ignatius R (2017) Increasing metronidazole and rifampicin resistance of Helicobacter pylori isolates obtained from children and adolescents between 2002 and 2015 in southwest Germany. Helicobacter 22:e12327. https://doi.org/10.1111/hel.12327
Nguyen TVH, Bengtsson C, Yin L, Nguyen GK, Hoang TTH,Phung DC, Sörberg M, Granström M (2012) Eradication of Helicobacter pylori in children in Vietnam in relation to antibiotic resistance. Helicobacter 17:319–325. https://doi.org/10.1111/j.1523-5378.2012.00950.x
Rafeey M, Ghotaslou R, Nikvash S, Hafez AA (2007) Primary resistance in Helicobacter pylori isolated in children from Iran. J Infect Chemother 13:291–295. https://doi.org/10.1007/s10156-007-0543-6
Megraud F, Coenen S, Versporten A, Kist M, Lopez-Brea M, Hirschl AM, Andersen LP, Goossens H, Glupczynski Y (2013) Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut 62:34–42. https://doi.org/10.1136/gutjnl-2012-302254
Kuo YT, Liou MJ, El Omar EM et al (2017) Primary antibiotic resistance in Helicobacter pylori in the Asia-Pacific region: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2:707–715. https://doi.org/10.1016/S2468-1253(17)30219-4
Prechtl J, Deutschmann A, Savic T, Jahnel J, Bogiatzis A, Muntean W, Hauer AC, Hoffmann KM (2012) Monitoring of antibiotic resistance rates of Helicobacter pylori in Austrian children, 2002–2009. Pediatr Infect Dis J 31:312–314. https://doi.org/10.1097/INF.0b013e31823d9490
Bardhan KD, Bayerdörffer E, Van Zanten SJV et al (2000) The HOMER study: the effect of increasing the dose of metronidazole when given with omeprazole and amoxicillin to cure Helicobacter pylori infection. Helicobacter 5:196–201. https://doi.org/10.1046/j.1523-5378.2000.00030.x
Papastergiou V, Georgopoulos SD, Karatapanis S (2014) Treatment of Helicobacter pylori infection: past, present and future. World J Gastrointest Pathophysiol 5:392–399. https://doi.org/10.4291/wjgp.v5.i4.392
Leng JY, Yuan GL, Tang Q, Shen W (2016) Analysis on drug resistance of Helicobacter pylori clinical isolates in Chongqing area of 2014. China Pharmacy 027:1487–1490
Xie Y, Zhu Y, Zhou H et al (2014) Furazolidone-based triple and quadruple eradication therapy for Helicobacter pylori infection. World J Gastroentero 20:11415–11421. https://doi.org/10.3748/wjg.v20.i32.11415
Riahizadeh S, Malekzadeh R, Agah S et al (2010) Sequential metronidazole-furazolidone or clarithromycin-furazolidone compared to clarithromycin-based quadruple regimens for the eradication of Helicobacter pylori in peptic ulcer disease: a double-blind randomized controlled trial. Helicobacter 15:497–504. https://doi.org/10.1111/j.1523-5378.2010.00798.x
Xie C, Lu NH (2015) clinical management of Helicobacter pylori infection in China. Helicobacter 20:1–10. https://doi.org/10.1111/hel.12178
López-Góngora S, Puig I, Calvet X, Villoria A, Baylina M, Muñoz N, Sanchez-Delgado J, Suarez D, García-Hernando V, Gisbert JP (2015) Systematic review and meta-analysis: susceptibility-guided versus empirical antibiotic treatment for Helicobacter pylori infection. J Antimicrob Chemoth 70:2447–2455. https://doi.org/10.1093/jac/dkv155
Cosme A, Montes M, Ibarra B, Tamayo E, Alonso H, Mendarte U, Lizasoan J, Herreros-Villanueva M, Bujanda L (2017) Antimicrobial susceptibility testing before first-line treatment for Helicobacter pylori infection in patients with dual or triple antibiotic resistance. World J Gastroentero 23:3367–3373. https://doi.org/10.3748/wjg.v23.i18.3367
Cho JH, Jeon SR, Kim HG, Jin SY, Park S (2019) Cost-effectiveness of a tailored Helicobacter pylori eradication strategy based on the presence of a 23 S ribosomal RNA point mutation that causes clarithromycin resistance in Korean patients. J Gastroen Hepatol 34:700–706. https://doi.org/10.1111/jgh.14383
Papastergiou V, Mathou N, Licousi S, Evgenidi A, Paraskeva KD, Giannakopoulos A, Stavrou PZ, Platsouka E, Karagiannis JA (2018) Seven-day genotypic resistance-guided triple Helicobacter pylori eradication therapy can be highly effective. Ann Gastroenterol 31:198–204. https://doi.org/10.20524/aog.2017.0219
Lauener FN, Imkamp F, Lehours P, Buissonnière A, Benejat L, Zbinden R, Keller PM, Wagner K (2019) Genetic determinants and prediction of antibiotic resistance phenotypes in Helicobacter pylori. J Clin Med 8:53. https://doi.org/10.3390/jcm8010053
Kanai K, Shibayama K, Suzuki S, Wachino JI, Arakawa Y (2004) Growth competition of macrolide-resistant and susceptible Helicobacter pylori strains. Microbiol Immunol 48:977–980. https://doi.org/10.1111/j.1348-0421.2004.tb03628.x
Klesiewicz K, Nowak P, Karczewska E, Skiba I, Wojtas-Bonior I, Sito E, Budak A (2014) PCR-RFLP detection of point mutations A2143G and A2142G in 23S rRNA gene conferring resistance to clarithromycin in Helicobacter pylori strains. Acta Biochim Pol 61:311–5
Gerrits MM, van Vliet AH, Kuipers EJ, Kusters JG (2006) Helicobacter pylori and antimicrobial resistance: molecular mechanisms and clinical implications. Lancet Infect Dis 6:699–709. https://doi.org/10.1016/S1473-3099(06)70627-2
Francavilla R, Lionetti E, Castellaneta S, Margiotta M, Piscitelli D, Lorenzo L, Cavallo L, Ierardi E (2010) Clarithromycin-resistant genotypes and eradication of Helicobacter pylori. J Pediatr 157:228–232. https://doi.org/10.1016/j.jpeds.2010.02.007.E
Arslan N, Yılmaz Ö, Demiray-Gürbüz E (2017) Importance of antimicrobial susceptibility testing for the management of eradication in Helicobacter pylori infection. World J Gastroenterol 23:2854–2869. https://doi.org/10.3748/wjg.v23.i16.2854
Vécsei A, Innerhofer A, Binder C, Gizci H, Hammer K, Bruckdorfer A, Riedl S, Gadner H, M. Hirschl A, Makristathis A (2010) Stool polymerase chain reaction for Helicobacter pylori detection and clarithromycin susceptibility testing in children. Clin Gastroenterol H 8:309–312. https://doi.org/10.1016/j.cgh.2009.12.002
Scaletsky IC, Aranda KR, Garcia GT, Gonçalves ME, Cardoso SR, Iriya K, Silva NP (2011) Application of real-time PCR stool assay for Helicobacter pylori detection and clarithromycin susceptibility testing in Brazilian children. Helicobacter 16:311–315. https://doi.org/10.1111/j.1523-5378.2011.00845.x
Funding
This study was supported by the Science and Health Joint Medical Research Program of Chongqing (2019ZDXM045).
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Tian Geng and Zhong-Su Yu conceived and designed the experiments, collected materials, analyzed and interpreted the data, drafted the manuscript. Xi-Xi Zhou, Hui-Hua Zhang, Bo Liu conceived and designed the experiments, collected materials. Zhong-Yue Li conceived and designed the experiments, analyzed and interpreted the data, drafted and revised the manuscript, and approved the final version.
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This study was approved by the Ethics Committee of Children’s Hospital of Chongqing Medical University (File No. 2017–36-1) and informed consent of the clinical trial was signed from legal guardians of the whole subjects.
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The original online version of this article was revised: the abbreviation for Metronidazole in the Tables 2, 3 and 5 has been corrected to MTZ.
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Geng, T., Yu, ZS., Zhou, XX. et al. Antibiotic resistance of Helicobacter pylori isolated from children in Chongqing, China. Eur J Pediatr 181, 2715–2722 (2022). https://doi.org/10.1007/s00431-022-04456-1
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DOI: https://doi.org/10.1007/s00431-022-04456-1