1887

Abstract

Antibiotic resistance is increasing worldwide, and it has been regarded as the main factor reducing the efficacy of therapy. The aim of this study was to determine the phenotype and genotype of antibiotic-resistant strains of in the Malaysian population and to evaluate the impact of antibiotic resistance to eradication outcome. One hundred and sixty-one isolates were analysed in this study. Metronidazole, clarithromycin, fluoroquinolone, amoxicillin and tetracycline susceptibilities were determined by Etest. PCR followed by DNA sequencing was carried out to determine mutations. The medical records of the patients infected with resistant strains were reviewed to determine the eradication outcome. Metronidazole resistance was encountered in 36.6 % of isolates, whereas clarithromycin and fluoroquinolone resistance was observed in 1.2  and 1.9 % of isolates, respectively. All strains tested were susceptible to amoxicillin and tetracycline. Frameshift and nonsense mutations in and genes resulting in stop codons contributed to metronidazole resistance, which leads to reduced eradication efficacy. A2142G and A2143G mutations of 23S rRNA were identified as causing failure of the eradication therapy. Mutation at either codon 87 or 91 of the gene was identified in fluoroquinolone-resistant strains. However, the effect of resistance could not be assessed. This study showed that frameshift and nonsense mutations in or genes and point mutations in the 23S rRNA affected the efficacy of eradication therapy.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.069781-0
2014-05-01
2024-03-19
Loading full text...

Full text loading...

/deliver/fulltext/jmm/63/5/703.html?itemId=/content/journal/jmm/10.1099/jmm.0.069781-0&mimeType=html&fmt=ahah

References

  1. Ahmad N., Zakaria W. R., Abdullah S. A., Mohamed R. 2009; Characterization of clarithromycin resistance in Malaysian isolates of Helicobacter pylori.. World J Gastroenterol 15:3161–3165 [View Article][PubMed]
    [Google Scholar]
  2. Ahmad N., Zakaria W. R., Mohamed R. 2011; Analysis of antibiotic susceptibility patterns of Helicobacter pylori isolates from Malaysia. Helicobacter 16:47–51 [View Article][PubMed]
    [Google Scholar]
  3. Atherton J. C. 2006; The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases. Annu Rev Pathol 1:63–96 [View Article][PubMed]
    [Google Scholar]
  4. Bago J., Majstorović K., Belosić-Halle Z., Kućisec N., Bakula V., Tomić M., Bago P., Troskot R. 2010; Antimicrobial resistance of H. pylori to the outcome of 10-days vs. 7-days moxifloxacin based therapy for the eradication: a randomized controlled trial. Ann Clin Microbiol Antimicrob 9:13 [View Article][PubMed]
    [Google Scholar]
  5. Cattoir V., Nectoux J., Lascols C., Deforges L., Delchier J. C., Megraud F., Soussy C. J., Cambau E. 2007; Update on fluoroquinolone resistance in Helicobacter pylori: new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility. Int J Antimicrob Agents 29:389–396 [View Article][PubMed]
    [Google Scholar]
  6. Chisholm S. A., Owen R. J. 2003; Mutations in Helicobacter pylori rdxA gene sequences may not contribute to metronidazole resistance. J Antimicrob Chemother 51:995–999 [View Article][PubMed]
    [Google Scholar]
  7. Chisholm S. A., Owen R. J. 2004; Frameshift mutations in frxA occur frequently and do not provide a reliable marker for metronidazole resistance in UK isolates of Helicobacter pylori.. J Med Microbiol 53:135–140 [View Article][PubMed]
    [Google Scholar]
  8. Chisholm S. A., Owen R. J. 2009; Frequency and molecular characteristics of ciprofloxacin- and rifampicin-resistant Helicobacter pylori from gastric infections in the UK. J Med Microbiol 58:1322–1328 [View Article][PubMed]
    [Google Scholar]
  9. De Francesco V., Margiotta M., Zullo A., Hassan C., Giorgio F., Burattini O., Stoppino G., Cea U., Pace A.& other authors ( 2007; Prevalence of primary clarithromycin resistance in Helicobacter pylori strains over a 15 year period in Italy. J Antimicrob Chemother 59:783–785 [View Article][PubMed]
    [Google Scholar]
  10. De Francesco V., Giorgio F., Hassan C., Manes G., Vannella L., Panella C., Ierardi E., Zullo A. 2010a; Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis 19:409–414[PubMed]
    [Google Scholar]
  11. De Francesco V., Zullo A., Ierardi E., Giorgio F., Perna F., Hassan C., Morini S., Panella C., Vaira D. 2010b; Phenotypic and genotypic Helicobacter pylori clarithromycin resistance and therapeutic outcome: benefits and limits. J Antimicrob Chemother 65:327–332 [View Article][PubMed]
    [Google Scholar]
  12. Debets-Ossenkopp Y. J., Herscheid A. J., Pot R. G. J., Kuipers E. J., Kusters J. G., Vandenbroucke-Grauls C. M. 1999; Prevalence of Helicobacter pylori resistance to metronidazole, clarithromycin, amoxycillin, tetracycline and trovafloxacin in The Netherlands. J Antimicrob Chemother 43:511–515 [View Article][PubMed]
    [Google Scholar]
  13. Gisbert J. P. 2009; Second-line rescue therapy of Helicobacter pylori infection. Therap Adv Gastroenterol 2:331–356 [View Article][PubMed]
    [Google Scholar]
  14. Hwang T. J., Kim N., Kim H. B., Lee B. H., Nam R. H., Park J. H., Lee M. K., Park Y. S., Lee D. H.& other authors ( 2010; Change in antibiotic resistance of Helicobacter pylori strains and the effect of A2143G point mutation of 23S rRNA on the eradication of H. pylori in a single center of Korea. J Clin Gastroenterol 44:536–543[PubMed]
    [Google Scholar]
  15. Kim J. J., Reddy R., Lee M., Kim J. G., El-Zaatari F. A., Osato M. S., Graham D. Y., Kwon D. H. 2001; Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates from Korea. J Antimicrob Chemother 47:459–461 [View Article][PubMed]
    [Google Scholar]
  16. Kim J. M., Kim J. S., Jung H. C., Kim N., Kim Y. J., Song I. S. 2004; Distribution of antibiotic MICs for Helicobacter pylori strains over a 16-year period in patients from Seoul, South Korea. Antimicrob Agents Chemother 48:4843–4847 [View Article][PubMed]
    [Google Scholar]
  17. Kim J. M., Kim J. S., Kim N., Jung H. C., Song I. S. 2005; Distribution of fluoroquinolone MICs in Helicobacter pylori strains from Korean patients. J Antimicrob Chemother 56:965–967 [View Article][PubMed]
    [Google Scholar]
  18. Kim J. M., Kim J. S., Kim N., Kim Y. J., Kim I. Y., Chee Y. J., Lee C. H., Jung H. C. 2008; Gene mutations of 23S rRNA associated with clarithromycin resistance in Helicobacter pylori strains isolated from Korean patients. J Microbiol Biotechnol 18:1584–1589[PubMed]
    [Google Scholar]
  19. Kobayashi I., Murakami K., Kato M., Kato S., Azuma T., Takahashi S., Uemura N., Katsuyama T., Fukuda Y.& other authors ( 2007; Changing antimicrobial susceptibility epidemiology of Helicobacter pylori strains in Japan between 2002 and 2005. J Clin Microbiol 45:4006–4010 [View Article][PubMed]
    [Google Scholar]
  20. Kwon D. H., El-Zaatari F. A., Kato M., Osato M. S., Reddy R., Yamaoka Y., Graham D. Y. 2000; Analysis of rdxA and involvement of additional genes encoding NAD(P)H flavin oxidoreductase (FrxA) and ferredoxin-like protein (FdxB) in metronidazole resistance of Helicobacter pylori. Antimicrob Agents Chemother 44:2133–2142 [View Article][PubMed]
    [Google Scholar]
  21. Lee J. H., Shin J. H., Roe I. H., Sohn S. G., Lee J. H., Kang G. H., Lee H. K., Jeong B. C., Lee S. H. 2005; Impact of clarithromycin resistance on eradication of Helicobacter pylori in infected adults. Antimicrob Agents Chemother 49:1600–1603 [View Article][PubMed]
    [Google Scholar]
  22. Llanes R., Soria C., Nagashima S., Kobayashi N., Gala A., Guzmán D., Feliciano O., Valdés L., Gutiérrez O.& other authors ( 2010; Phenotypic and genetic characterization of antimicrobial profiles of Helicobacter pylori strains in Cuba. J Health Popul Nutr 28:124–129 [View Article][PubMed]
    [Google Scholar]
  23. Malfertheiner P., Megraud F., O’Morain C., Bazzoli F., El-Omar E., Graham D., Hunt R., Rokkas T., Vakil N., Kuipers E. J. 2007; Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 56:772–781 [View Article][PubMed]
    [Google Scholar]
  24. Marais A., Bilardi C., Cantet F., Mendz G. L., Mégraud F. 2003; Characterization of the genes rdxA and frxA involved in metronidazole resistance in Helicobacter pylori.. Res Microbiol 154:137–144 [View Article][PubMed]
    [Google Scholar]
  25. Matteo M. J., Pérez C. V., Domingo M. R., Olmos M., Sanchez C., Catalano M. 2006; DNA sequence analysis of rdxA and frxA from paired metronidazole-sensitive and -resistant Helicobacter pylori isolates obtained from patients with heteroresistance. Int J Antimicrob Agents 27:152–158 [View Article][PubMed]
    [Google Scholar]
  26. Mégraud F. 2004; H pylori antibiotic resistance: prevalence, importance, and advances in testing. Gut 53:1374–1384 [View Article][PubMed]
    [Google Scholar]
  27. Mégraud F., Lehours P. 2007; Helicobacter pylori detection and antimicrobial susceptibility testing. Clin Microbiol Rev 20:280–322 [View Article][PubMed]
    [Google Scholar]
  28. Ministry of Health Malaysia 2008 National Antibiotic Guideline Putrajaya: Ministry of Health Malaysia;
    [Google Scholar]
  29. Nahar S., Mukhopadhyay A. K., Khan R., Ahmad M. M., Datta S., Chattopadhyay S., Dhar S. C., Sarker S. A., Engstrand L.& other authors ( 2004; Antimicrobial susceptibility of Helicobacter pylori strains isolated in Bangladesh. J Clin Microbiol 42:4856–4858 [View Article][PubMed]
    [Google Scholar]
  30. Rajper S., Khan E., Ahmad Z., Alam S. M. Z., Akbar A., Hasan R. 2012; Macrolide and fluoroquinolone resistance in Helicobacter pylori isolates: an experience at a tertiary care centre in Pakistan. J Pak Med Assoc 62:1140–1144[PubMed]
    [Google Scholar]
  31. Seck A., Mbengue M., Gassama-Sow A., Diouf L., Ka M. M., Boye C. S. B. 2009; Antibiotic susceptibility of Helicobacter pylori isolates in Dakar, Senegal. J Infect Dev Ctries 3:137–140 [View Article][PubMed]
    [Google Scholar]
  32. Solcà N. M., Bernasconi M. V., Piffaretti J. C. 2000; Mechanism of metronidazole resistance in Helicobacter pylori: comparison of the rdxA gene sequences in 30 strains. Antimicrob Agents Chemother 44:2207–2210 [View Article][PubMed]
    [Google Scholar]
  33. Sun Q. J., Liang X., Zheng Q., Gu W. Q., Liu W. Z., Xiao S. D., Lu H. 2010; Resistance of Helicobacter pylori to antibiotics from 2000 to 2009 in Shanghai. World J Gastroenterol 16:5118–5121 [View Article][PubMed]
    [Google Scholar]
  34. Tankovic J., Lascols C., Sculo Q., Petit J. C., Soussy C. J. 2003; Single and double mutations in gyrA but not in gyrB are associated with low- and high-level fluoroquinolone resistance in Helicobacter pylori.. Antimicrob Agents Chemother 47:3942–3944 [View Article][PubMed]
    [Google Scholar]
  35. Wueppenhorst N., Stueger H. P., Kist M., Glocker E. 2009; Identification and molecular characterization of triple- and quadruple-resistant Helicobacter pylori clinical isolates in Germany. J Antimicrob Chemother 63:648–653 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.069781-0
Loading
/content/journal/jmm/10.1099/jmm.0.069781-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error