Claritromycin Resistance and Helicobacter pylori Genotypes in Italy

  • Francesco Vincenzo De (Gastroenterology Unit, 'Riuniti' Hospital) ;
  • Margiotta Marcella (Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari) ;
  • Zullo Angelo (Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital) ;
  • Hassan Cesare (Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital) ;
  • Valle Nicolar Della (Section of Gastroenterology, Department of Medical Sciences, University of Foggia) ;
  • Burattini Osvaldo (Section of Gastroenterology, Department of Medical Sciences, University of Foggia) ;
  • D'Angel Roberto (Section of Gastroenterology, Department of Medical Sciences, University of Foggia) ;
  • Stoppino Giuseppe (Section of Gastroenterology, Department of Medical Sciences, University of Foggia) ;
  • Cea Ugo (Section of Gastroenterology, Department of Medical Sciences, University of Foggia) ;
  • Giorgio Floriana (Section, of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari) ;
  • Monno Rosa (Section of microbiology, Department of Hygiene and Public Health, University of Bari) ;
  • Morini Sergio (Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital) ;
  • Panella Carmine (Section of Gastroenterology, Department of Medical Sciences, University of Foggia)
  • Published : 2006.12.31

Abstract

The relationship between H. pylori clarithromycin resistance and genetic pattern distribution has been differently explained from different geographic areas. Therefore, we aimed to assess the clarithromycin resistance rate, to evaluate the bacterial genetic pattern, and to search for a possible association between clarithromycin resistance and cagA or vacA genes. This prospective study enrolled 62 consecutive H. pylori infected patients. The infection was established by histology and rapid urease test. Clarithromycin resistance, cagA and vacA status, including s/m subtypes, were assessed on paraffin-embedded antral biopsy specimens by TaqMan real time polymerase chain reaction (PCR). Primary clarithromycin resistance was detected in 24.1 % of cases. The prevalence of cagA was 69.3%, and a single vacA mosaicism was observed in 95.1 % cases. In detail, the s1m1 was observed in 23 (38.9%) patients, the s1m2 in 22 (37.2%), and the s2m2 in 14 (23.7%), whereas the s2m1 combination was never found. The prevalence of cagA and the vacA alleles distribution did not significantly differ between susceptible and resistant strains. Primary clarithromycin resistance is high in our area. The s1m1 and s1m2 are the most frequent vacA mosaicisms. There is no a relationship between clarithromycin resistance and bacterial genotypic pattern and/or cagA positivity.

Keywords

References

  1. Alm, R.A., L.S. Ling, D.T. Moir, B.L. King, E.D. Brown, P.C. Doig, D.R. Smith, B. Noonan, B.C. Guild, B.L. de Jonge, G. Carmel, P.J. Tummino, A. Caruso, M. Uria-Nickelsen, D.M. Mills, C. Ives, R. Gibson, D. Merberg, S.D. Mills, Q. Jiang, et al. 1999. Genomic sequence comparison of two unrelated isolated of the human gastric pathogen Helicobacter pylori. Nature 397, 176-180 https://doi.org/10.1038/16495
  2. Atherton, J.C., P. Cao, R.M. Peek, Jr, M.K. Tummuru, M.J. Blaser, and T.L. Cover. 1995 Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J. Biol. Chem. 270, 17771-17777 https://doi.org/10.1074/jbc.270.30.17771
  3. Cellini, L., R. Grande, E. Di Campli, S. Di Bartolomeo, S. Capodocasa, and L. Marzio. 2006. Analysis of genetic variability, antimicrobial susceptibility and virulence markers in Helicobacter pylori identified in Central Italy. Scand. J. Gastroenterol. 41. 280-287 https://doi.org/10.1080/00365520510024223
  4. Covacci, A., J.L. Telford, G. Del Giudice, J. Parsonnet, and R. Rappuoli. 1999. Helicobacter pylori virulence and genetic geography. Science 284, 1328-1333 https://doi.org/10.1126/science.284.5418.1328
  5. Crabtree, J.E., N. Figura, J.D. Taylor, M. Bugnoli, D. Armellini, and D.S. Tompkins. 1992. Expression of 120 kilodalton protein and cytotoxicity in Helicobacter pylori. J. Clin. Pathol. 45, 733-734 https://doi.org/10.1136/jcp.45.8.733
  6. De Francesco, V., A. Zullo, M. Margiotta, S. Marangi, O. Burattini, P. Berloco, F. Russo, M. Barone, A. Di Loe, M.F. Minenna, V. Stoppino, S. Morini, C. Panella, A. Francavilla, and E. Ierardi. 2004. Sequential treatment for Helicobacter pylori does not share the risk factors of triple therapy failure. Aliment Pharmacol. Ther. 19, 407-414 https://doi.org/10.1046/j.1365-2036.2004.01818.x
  7. De Francesco, V., M. Margiotta, A. Zullo, C. Hassan, N. Della Valle, O. Burattini, U. Cea, G. Stoppino, A. Amoruso, F. Stella, S. Morini, C. Panella, and E. Ierardi. 2006a. Primary clarithromycin resistance in Italy assessed on Helicobacter pylori DNA sequences by TaqMan real time polymerase chain reaction. Aliment Pharmacol. Ther. 23, 429-435 https://doi.org/10.1111/j.1365-2036.2006.02769.x
  8. De Francesco, V., M. Margiotta, A. Zullo, C. Hassan, L. Troiani, O. Burattini, F. Stella, A. Di leo, F. Russo, S. Marangi, R. Monno, V. Stoppino, S. Morini, C. Panella, and E. Ierardi. 2006b. Clarithromycin-resistant genotypes and eradication of Helicobacter pylori. Ann. Intern. Med. 144, 94-100 https://doi.org/10.7326/0003-4819-144-2-200601170-00006
  9. Elviss, N.C., R.J. Owen, J. Xerry, A.M. Walker, and K. Davies. 2004 Helicobacter pylori antibiotic resistance patterns and genotypes in adult dyspeptic patients from a regional population in North Wales. J. Antimicrob. Chemother. 54, 435-440 https://doi.org/10.1093/jac/dkh343
  10. Godoy, A.P., M.L. Ribeiro, Benvengo, L. Vitiello, C. Miranda Mde, S. Mendonca, J. Pedrazzoli, Jr. 2003. Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates. BMC Gastroenterol. 3, 1-6 https://doi.org/10.1186/1471-230X-3-1
  11. Han, S.R., H.J. Schreiber, S. Bhakdi, M. Loos, and M.J. Maeurer. 1998. vacA genotypes and genetic diversity in clinical isolates of Helicobacter pylori. Clin. Diagn. Lab. Immunol. 5, 139-145
  12. Kauser, F., M.A. Hussain, I. Ahmed, S. Srinivas, S.M. Devi, A.A. Majeed, K.R. Rao, A.A. Khan, L.A. Sechi and N. Ahmed. 2005. Comparative genomics of Helicobacter pylori isolates recovered from ulcer disease patients in England. BMC Microbiol. 5, 32-35 https://doi.org/10.1186/1471-2180-5-32
  13. Kim, J.J., J.G. Kim, and D.H. Kwon. 2003. Mixed-infection of antibiotic susceptible and resistant Helicobacter pylori isolates in a single patient and underestimation of antimicrobial susceptibility testing. Helicobacter 8, 202-206 https://doi.org/10.1046/j.1523-5378.2003.00145.x
  14. Lascols, C., D. Lamarque, J.M. Costa, C. Copie-Bergman, J.M. Le Glaunec, L. Deforges, C.J. Soussy, J.C. Petit, J.C. Delchier, and J. Tankovic. 2003. Fast and accurate quantitative detection of Helicobater pyloriand identification of clarithromycin resistance mutations in H. pylori isolates from gastric biopsy specimens by real-time PCR. J. Clin. Microbiol. 41, 4573-4577 https://doi.org/10.1128/JCM.41.10.4573-4577.2003
  15. Megraud, F. 2004. H. pyloriantibiotic resistance: prevalence, importance, and advances in testing. Gut 53, 1374-1384 https://doi.org/10.1136/gut.2003.022111
  16. Morales-Espinosa, R., G. Castillo-Rojas, G. Gonzalez-Valencia, G. Gonzalez-Valencia, S. P. de Leon, A. Cravioto, J.C. Atherton, and Y. Lopez-Vidal. 1999. Colonization of Mexican patients by multiple Helicobacter pylori strains with different vacA and cagA genotypes. J. Clin. Microbiol. 37, 3001-3004
  17. Perri, F., M.R. Villani, V. Festa, M. Quitadamo, and A. Andriulli. 2001. Predictors of failure of Helicobacter pylori eradication with the standard 'Maastricht triple therapy'. Aliment. Pharmacol. Ther. 15, 1023-1029 https://doi.org/10.1046/j.1365-2036.2001.01006.x
  18. Pilotto, A., M. Rassu, G. Leandro, M. Franceschi, and F. Di Mario. 2000. Prevalence of Helicobacter pyloriresistance to antibiotics in Northeast Italy: a multicentre study. Dig. Liver Dis. 32, 763-768 https://doi.org/10.1016/S1590-8658(00)80352-7
  19. Savarino, V., P. Zentilin, M. Pivari, G. Bisso, R. Mele, N. Pandolfo, V. Pugliese, and S. Vigneri. 2000. The impact of antibiotic resistance on the efficacy of three 7-day regimens against Helicobacter pylori. Aliment Pharmacol. Ther. 14, 893-900 https://doi.org/10.1046/j.1365-2036.2000.00780.x
  20. Toracchio, S. and L. Marzio. 2003. Primary and secondary antibiotic resistance of Helicobacter pylori strains isolated in central Italy during the years 1998-2002. Dig. Liver Dis. 35, 541-545 https://doi.org/10.1016/S1590-8658(03)00265-2
  21. Tummuru, M.K.R., T.L. Cover, and M.J. Blaser. 1993. Cloning and expression of a high molecular mass major antigen of Helicobacter pylori. Infect. Immun. 61, 1799-1809
  22. van Doorn, L.J., C. Figueiredo, R. Sanna, A. Plaisier, P. Schneeberger, W. de Boer, and W. Quint. 1998. Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology 115, 58-66 https://doi.org/10.1016/S0016-5085(98)70365-8
  23. van Doorn, L.J., Y. Glupczynski, J.G. Kusters, F. Megraud, P. Midolo, N. Maggi-Solca, D.M. Queiroz, N. Nouhan, E. Stet, and W.G. Quint. 2001. Accurate prediction of macrolide resistance in Helicobater pylori by a PCR line probe assay for detection of mutations in the 23S rRNA gene: multicenter validation study. Antimicrob Agents Chemother 45, 1500-1504 https://doi.org/10.1128/AAC.45.5.1500-1504.2001
  24. Wada, T., S. Maeda, A. Tamaru, S. Imai, A. Hase, and K. Kobayashi. 2004. Dual-probe assay for rapid detection of drug resistant Mycobacterium tuberculosis by Real-Time PCR. J. Clin. Microbiol. 42, 5277-5278 https://doi.org/10.1128/JCM.42.11.5277-5285.2004
  25. Weel, J.F., R.W. van der Hulst, Y. Gerrits, P. Roorda, M. Feller, J. Dankert, G.N. Tytgat, and A. van der Ende. 1996. The interrelationship between cytotoxin-associated gene A, vacuolating cytotoxin, and Helicobacter pylorirelated diseases. J. Infect Dis. 173, 1171-1175 https://doi.org/10.1093/infdis/173.5.1171
  26. Yakoob, J., X.G. Fan, G.L. Hu, and Z. Zhang. 2004. Genetic and phenotype changes following in vitro interactions between Helicobacter pylori strains. J. Gastroenterol. Hepatol. 19, 626-631 https://doi.org/10.1111/j.1440-1746.2004.03352.x
  27. Yakoob, J., X.G. Fan, G.L. Hu, H.X. Yang, L. Liu, S.H. Liu, D.M. Tan, T.G. Li, and Z. Zhang. 2001. Polycolonization of Helicobacter pylori among Chinese subjects. Clin. Microbiol. Infect. 7, 187-192 https://doi.org/10.1046/j.1198-743x.2001.00226.x