Fuat AYDIN, Mustafa AKAR, Tuba KAYMAN, Emre KARAKAYA, Seçil ABAY

Detection of Helicobacter pylori by invasive tests in adult dyspeptic patients and antibacterial resistance to six antibiotics, including rifampicin in Turkey. Is clarithromycin resistance rate decreasing?

Background/aim: The prevalence of Helicobacter pylori is reported to be roughly 80% in Turkey, and only very few culture-based studies are available on antibacterial resistance in adult dyspeptic patients. This study was carried out in adult dyspeptic patients with an aim to: (i) detect H. pylori by invasive tests (culture, polymerase chain reaction, and histopathology) and (ii) determine the current resistance rates of H. pylori isolates to six antibiotics, including rifampicin. Materials and methods: This study was conducted in 422 adult dyspeptic patients. The presence of H. pylori was demonstrated by culture, polymerase chain reaction, and the histopathology of gastric biopsy material. Antibacterial susceptibility was determined with the E-test. Results: The mean age of the patients was 50 ± 15 (range 18–90), and 265 (63%) of them were female. By culture, polymerase chain reaction, and histopathology, the presence of H. pylori was detected at rates of 35% (148/422), 67% (281/422), and 53% (224/422), respectively. The prevalence of H. pylori was determined as 75.6% (319/422). Metronidazole, levofloxacin, clarithromycin, and rifampicin resistance rates were 62%, 36%, 19%, and 12%, respectively. Monodrug, dual-drug, and multidrug resistance rates were ascertained as 36.9%, 29.4%, and 10.5%, respectively. All of the isolates were susceptible to amoxicillin and tetracycline. Conclusion: This study revealed the current prevalence of H. pylori in adult dyspeptic patients as 75.6%, and thereby, showed that infection with this pathogen remains highly prevalent. Although resistance to metronidazole and levofloxacin has increased over time, clarithromycin resistance rate has decreased. The high levels of resistance to metronidazole and levofloxacin limit the empirical use of these antibiotics in the eradication protocol. Owing to the low level of resistance determined for rifampicin, this antibiotic could be included in the eradication protocol, in the event of the need for rescue therapy in Turkey.Key words: Antibacterial resistance, clarithromycin, Helicobacter pylori, invasive test, rifampicin, Turkey

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1. Magalhães Queiroz DM, Luzza F. Epidemiology of Helicobacter pylori infection. Helicobacter 2006; 11 (Suppl. 1): 1-5. doi: 10.1111/j.1478-405X.2006.00429.x
2. Xia HH, Talley NJ. Natural acquisition and spontaneouse limination of Helicobacter pylori infection: clinical implications. The American Journal of Gastroenterology 1997; 92 (10): 1780-1787.
3. Beswick EJ, Suarez G, Reyes VE. Helicobacter pylori and host interactions that influence pathogenesis. World Journal ofGastroenterology 2006; 12: 5599-5605. doi: 10.3748/wjg.v12. i35.5599
4. Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT et al. Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report. Gut 2012; 61: 646- 664. doi: 10.1136/gutjnl-2012-302084
5. Malfertheiner P, Chan FK, McColl KE. Peptic ulcer disease. Lancet 2009; 374: 1449-1461. doi: 10.1016/S0140- 6736(09)60938-7
6. Malfertheiner P, Megraud F, O’Morain CA, Gisbert JP, Kuipers EJ et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut 2017; 66: 6-30. doi: 10.1136/gutjnl-2016-312288
7. Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM et al. Kyoto global consensusreport on Helicobacter pylori gastritis. Gut 2015; 64: 1353-1367. doi: 10.1136/gutjnl-2015-309252
8. McMahon BJ, Bruce MG, Koch A, Goodman KJ, Tsukanov V et al. The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: expert commentary. Epidemiology and Infection 2016; 144 (2): 225-233. doi: 10.1017/S0950268815001181
9. Wang YK, Kuo FC, Liu CJ, Wu MC, Shih HY et al. Diagnosis of helicobacter pylori infection: current options and developments. World Journal of Gastroenterology 2015; 21 (40): 11221-11235. doi: 10.3748/wjg.v21.i40.11221
10. Kim SG, Jung HK, Lee HL, Jang JY, Lee H et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. Journal of Gastroenterology and Hepatology 2014; 29 (7): 1371-1386. doi: 10.1111/jgh.12607
11. Bezmin Abad AT. Diagnosis of Helicobacter pylori using invasive and noninvasive approaches. Journal of Pathogens 2018; 2018: 9064952. doi: 10.1155/2018/9064952
12. Arslan N, Yılmaz Ö, Demiray-Gürbüz E. Importance of antimicrobial susceptibility testing for the management of eradication in Helicobacter pylori infection. World Journal of Gastroenterology 2017; 23 (16): 2854-2869. doi: 10.3748/wjg. v23.i16.2854
13. Savoldi A, Carrara E, Graham DY, Tacconelli E. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization regions. Gastroenterology 2018; 155 (5): 1372-1382. doi: 10.1053/j. gastro.2018.07.007
14. Bakır Özbey S, Özakın C, Keskin M. Antibiotic resistance rates of Helicobacter pylori isolates and the comparison of E-test and fluorescent in situ hybridization methods for the detection of clarithromycin resistant strains. Mikrobiyoloji Bulteni 2009; 43: 227-234 (in Turkish).
15. Benoit A, Hoyeau N, Fléjou JF. Diagnosis of Helicobacter pylori infection on gastric biopsies: standard stain, special stain or immunohistochemistry? Annales de Pathologie 2018; 38 (6): 363-369. doi: 10.1016/j.annpat.2018.03.009
16. Macías-García F, Llovo-Taboada J, Díaz-López M, Bastón-Rey I, Domínguez-Muñoz JE. High primary antibiotic resistance of Helicobacter Pylori strains isolated from dyspeptic patients: a prevalence cross-sectional study in Spain. Helicobacter 2017; 22 (6). doi: 10.1111/hel.12440
17. Public Health England. UK Standards for Microbiology Investigations. Identification of Helicobacter species. Bacteriology identification: 26. Issue no: 3. London, England: Public Health England (Standards Unit, Microbiology Services); 2015. pp. 1-27.
18. Lu JJ, Perng CL, Shyu RY, Chen CH, Lou Qet al. Comparison of five PCR methods for detection of Helicobacter pylori DNA in gastrict issues. Journal of Clinical Microbiology 1999; 37: 772-774. doi: 10.1128/JCM.37.3.772-774.1999
19. The European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters Version 10.0, valid from 2020-01-01. Vaxjo, Sweden: EUCAST; 2020.
20. Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology 2017; 153 (2): 420-429. doi: 10.1053/j.gastro.2017.04.022
21. Ozaydin N, Turkyilmaz SA, Cali S. Prevalence and risk factors of Helicobacter pylori in Turkey: a nationally-representative, cross-sectional, screening with the ¹³C-urea breath test. BMC Public Health 2013; 13: 1215. doi: 10.1186/1471-2458-13-1215
22. Sarnelli G, Cuomo R, Janssens J, Tack J. Symptom patterns and pathophysiological mechanisms in dyspeptic patients with and without Helicobacter pylori. Digestive Diseases and Sciences 2003; 48 (12): 2229-2236. doi: 10.1023/b:ddas.0000007856.71462.6c
23. Duggan AE, Elliott CA, Miller P, Hawkey CJ, Logan RF. Clinical trial: a randomized trial of early endoscopy, Helicobacter pylori testing and empirical therapy for the management of dyspepsia in primary care. Alimentary Pharmacology & Therapeutics 2009; 29 (1): 55-68. doi: 10.1111/j.1365-2036.2008.03852.x
24. Hamrah MH, Hamrah MS, Hassan Hamrah M, Kanda M, Hamrah AE et al. Prevalence of Helicobacter pylori infection in dyspeptic patients in Andkhoy Afghanistan. Asian Pacific Journal of Cancer Prevention 2017; 18 (11): 3123‐3127. doi: 10.22034/APJCP.2017.18.11.3123
25. Dorji D, Dendup T, Malaty HM, Wangchuk K, Yangzom D et al. Epidemiology of Helicobacter pylori in Bhutan: the role of environment and geographic location. Helicobacter 2014; 19 (1): 69-73. doi: 10.1111/hel.12088
26. Ozdil K, Sahin A, Kahraman R, Yuzbasioglu B, Demirdag H et al. Current prevalence of intestinal metaplasia and Helicobacter pylori infection in dyspeptic adult patients from Turkey. Hepatogastroenterology 2010; 57 (104): 1563-1566.
27. Erkut M, Uzun DY, Kaklıkkaya N, Fidan S, Yoğun Yet al. Sociodemographic characteristics and clinical risk factors of Helicobacterpylori infection and antibiotic resistance in the Eastern Black Sea region of Turkey. Turkish Journal of Gastroenterology 2020; 31 (3): 221-233. doi: 10.5152/ tjg.2020.18631
28. Kekilli M, Onal IK, Ocal S, Dogan Z, Tanoglu A. Inefficacy of triple therapy and comparison of two different bismuthcontaining quadruple regimens as a first line treatment option for Helicobacter pylori. Saudi Journal of Gastroenterology 2016; 22 (5): 366-369. doi: 10.4103/1319-3767.191141
29. Kaplan M, Tanoglu A, Duzenli T, Tozun AN. Helicobacter pylori treatment in Turkey: Current status and rational treatment options. Nothern Clinics of İstanbul 2019; 7 (1): 87-94. doi: 10.14744/nci.2019.62558
30. Sezgin O, Aydın MK, Özdemir AA, Kanık AE. Standard tripletherapy in Helicobacter pylori eradication in Turkey: systematic evaluation and meta-analysis of 10-year studies. Turkish Journal of Gastroenterology 2019; 30 (5): 420-435. doi: 10.5152/tjg.2019.18693
31. O’Connor A, Liou JM, Gisbert JP, O’Morain C. Review: treatment of Helicobacter pylori infection 2019. Helicobacter 2019; 24 (Suppl. 1): e12640. doi: 10.1111/hel.12640
32. Smith SM, O’Morain C, McNamara D. Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance. World Journal of Gastroenterology 2014; 20: 9912-9921. doi: 10.3748/wjg.v20.i29.9912
33. Cammarota G, Ianiro G, Bibbò S, DiRienzo TA, Masucci L et al. Culture-guided treatment approach for Helicobacter pylori infection: review of the literature. World Journal of Gastroenterology 2014; 20: 5205-5211. doi: 10.3748/wjg.v20. i18.5205
34. O’connor A, Taneike I, Nami A, Fitzgerald N, Murphy P et al. Helicobacterpylori resistance to metronidazole and clarithromycin in Ireland. European Journal of Gastroenterology & Hepatology 2010; 22 (9): 1123-1127. doi: 10.1097/MEG.0b013e328338e43d
35. López-Góngora S, Puig I, Calvet X, Villoria A, Baylina M et al. Systematic review and meta-analysis: susceptibility-guided versus empirical antibiotic treatment for Helicobacter pylori infection. Journal of Antimicrobial Chemotherapy 2015; 70: 2447-2455. doi: 10.1093/jac/dkv155
36. Megraud F, Huang T, Wittkop L, Hoebeke M, Alix C et al. European survey of Helicobacter pylori primary resistance to antibiotics: evolution over the last 20 years. In: 30th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID);Paris, France; 2020. Absctract number: 10000.
37. De Francesco V, Giorgio F, Hassan C, Manes G, Vannella Let al. Worldwide Helicobacter pylori antibiotic resistance: a systematic review. Journal of Gastrointestinal and Liver Diseases 2010; 19 (4): 409-414.
38. Khademi F, Sahebkar A. An updated systematic review and meta-analysis on the Helicobacter pylori antibiotic resistance in Iran (2010-2020). Microbial Drug Resistance 2020. doi: 10.1089/mdr.2020.0088
39. Regnath T, Raecke O, Enninger A, Ignatius R. Increasing metronidazole and rifampicin resistance of Helicobacter pylori isolates obtained from children and adolescents between 2002 and 2015 in southwest Germany. Helicobacter 2017; 22 (1). doi: 10.1111/hel.12327
40. Martinez-Gonzalez B, Georgopoulos S, Michopoulos S, Karayiannis Y, Liatsos C et al. Multicenter survey of antimicrobial resistance in Helicobacter pylori isolates in Greece—Trends of resistance 1998–2018. XXXIInd Int. Work. Helicobacter Microbiota Inflamm. Cancer 2019; 24: e12647.
41. Kuo YT, LiouJM, El-Omar EM, Wu JY, Leow AHR et al. Primary antibiotic resistance in Helicobacter pylori in the AsiaPacific region: a systematic review and meta-analysis. Lancet Gastroenterology and Hepatology 2017; 2 (10): 707-715. doi: 10.1016/S2468-1253(17)30219-4
42. Gemilyan M, Hakobyan G, Benejat L, Allushi B, MelikNubaryan D et al. Prevalence of Helicobacter pylori infection and antibiotic resistance profile in Armenia. Gut Pathogens 2019; 11: 28. doi: 10.1186/s13099-019-0310-0
43. Boyanova L, Gergova G, Evstatiev I, Spassova Z, Kandilarov N et al. Helicobacter pylori resistance to six antibiotics by two breakpoint systems and resistance evolution in Bulgaria. Infectious Diseases 2016; 48 (1): 56-62. doi: 10.3109/23744235.2015.1082035
44. Caliskan R, Tokman HB, Erzin Y, Saribas S, Yuksel Pet al. Antimicrobial resistance of Helicobacter pylori strains to five antibiotics, including levofloxacin, in Northwestern Turkey. Revista da Sociedade Brasileira de Medicina Tropical 2015; 48 (3): 278-284. doi: 10.1590/0037-8682-0027-2015
45. Kocazeybek B, Sakli MK, Yuksel P, Demirci M, Caliskan Ret al. Comparison of new and classical point mutations associated with clarithromycin resistance in Helicobacter pylori strains isolated from dyspeptic patients and their effects on phenotypic clarithromycin resistance. Journal of Medical Microbiology 2019; 68 (4): 566-573. doi: 10.1099/jmm.0.000944
46. Çağdaş U, Otağ F, Tezcan S, Sezgin O, Aslan G et al. Detection of Helicobacter pylori and antimicrobial resistance in gastric biopsy specimens. Mikrobiyoloji Bülteni 2012; 46: 398-409 (in Turkish).