Journal List > Korean J Lab Med > v.26(3) > 1011310

Sung, Chung, Kim, and Lee: Clinical Usefulness of Antimicrobial Susceptibility Test for Helicobacter pylori

Abstract

Background

Antimicrobial resistance of Helicobacter pylori is considered as the main cause of failure of eradication therapy. Because resistance to metronidazole has been reported in 25.8% to 66.2% of H. pylori, a combination of proton pump inhibitors (PPI), amoxicillin, and clarithromycin is currently recommended as a primary therapy. We investigated the prevalence of antimicrobial resistance to the primary drugs and the impact of antimicrobial resistance on eradication rates.

Methods

Between May and August 2005, H. pylori isolates from 93 patients were tested for antimicrobial susceptibility at Asan Medical Center. Susceptibility tests of clarithromycin and amoxicillin were performed by the disk diffusion method and those of metronidazole and tetracycline by Etest (AB Biodisk, Solna, Sweden). The medical records of the patients were reviewed to collect the data such as demographic findings, previous and current eradication therapies, and bacteriological outcome. The appropriate therapy was defined as three-drug-combination including susceptible drugs only, or four-drug-combination including metronidazole in the case of metronidazole-resistance.

Results

Resistance rates to clarithromycin and metronidazole were 17.2% and 33.3%, respectively, but there was no resistance to tetracycline and amoxicillin. The eradication was successful in 32 of the 36 patients (88.9%) who received the appropriate therapy, but none of 4 patients who received an inappropriate therapy (P<0.01).

Conclusions

Resistance to clarithromycin seemed to increase and contribute to the failure of eradication therapy. For the appropriate therapy of H. pylori infection, the susceptibility results should be reported before initiation of the eradication therapy.

References

1. NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. JAMA. 1994; 272:65–9.
2. Blaser MJ. Hypothesis: the changing relationships of Helicobacter pylori and humans: implications for health and disease. J Infect Dis. 1999; 179:1523–30.
3. Boyanova L, Mentis A, Gubina M, Rozynek E, Gosciniak G, Kalenic S, et al. The status of antimicrobial resistance of Helicobacter pylori in eastern Europe. Clin Microbiol Infect. 2002; 8:388–96.
4. Kim JH, Kim HY, Kim NY, Kim SW, Kim JG, Kim JJ, et al. Seroprevalence of Helicobacter pylori infection in asymptomatic people in Korea. Korean J Med. 2000; 59:388–97.
5. Kim JG. Treatment of Helicobacter pylori infection. Korean J Gastroenterol. 2005; 46:172–80.
6. Kim JH. Treatment of Helicobacter pylori infection. Korean J Med. 2000; 58:378–85.
7. Kim JJ, Reddy R, Lee M, Kim JG, El-Zaatari FA, Osato MS, et al. Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates from Korea. J Antimicrob Chemother. 2001; 47:459–61.
8. Kim JM, Kim JS, Jung HC, Kim N, Song IS. Antibiotic resistance of Helicobacter pylori isolated from Korean patients in 2003. Korean J Gastroenterol. 2004; 44:126–35.
9. Lee J, Kim SM, Im EH, Choi YW, Kim YM, Kim PS, et al. The prevalence of antimicrobial resistance in Helicobacter pylori isolated in Daejeon. Korean J Clin Microbiol. 2005; 8:47–50.
10. Nam SW, Roe IH, Kim SB, Lee BS, Hwang YJ, Park HJ, et al. Detection of Clarithromycin-Resistant Helicobacter pylori by Polymerase Chain Reaction. Korean J Gastroenterol. 2000; 36:450–6.
11. Han DS, Cho YJ, Son JH, Park KN, Kang JO. Antimicrobial resistance of Helicobacter pylori in Korean patients with duodenal ulcer. Korean J Gastroenterol. 1997; 29:727–33.
12. Song HJ, Jung IS, Kim SW, Lee GM, Kim BW, Lee DS, et al. Antimicrobial resistance rates in Helicobacter pylori and detection of 23S rRNA mutation associated with clarithromycin resistance. Korean J Gastroenterol. 2000; 36:597–606.
13. Eun CS, Han DS, Park JY, Jeon YC, Hahm JS, Kim KS, et al. Changing pattern of antimicrobial resistance of Helicobacter pylori in Korean patients with peptic ulcer diseases. J Gastroenterol. 2003; 38:436–41.
14. Kim SJ, Kim JG, Jung K, Hong YH, Kim JH, Jung HR, et al. Antimicrobial resistance rate of Helicobacter pylori isolates and detection of mechanism of clarithromycin resistance. Korean J Med. 2001; 61:470–8.
15. Kim JM, Kim JS, Jung HC, Kim N, Kim YJ, Song IS. Distribution of antibiotic MICs for Helicobacter pylori strains over a 16-year period in patients from Seoul, South Korea. Antimicrob Agent Chemother. 2004; 48:4843–7.
16. De Boer WA, Driessen WM, Tytgat GN. Only four days of quadruple therapy can effectively cure Helicobacter pylori infection. Aliment Pharmacol Ther. 1995; 9:633–8.
17. Lee DH. Current status and treatment of Helicobacter pylori infection in Korea. Korean J Gastroenterol. 2002; 39:153–60.
18. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: fifteenth informational supplement for NCCLS. Document M7-A6, M100-S15.Wayne, Pa: Clinical and Laboratory Standard Institute;2005.
19. Lang L, Garcia F. Comparison of E-test and disk diffusion assay to evaluate resistance of Helicobacter pylori isolates to amoxicillin, clarithromycin, metronidazole and tetracycline in Costa Rica. Int J Antimicrob Agents. 2004; 24:572–7.
20. Megraud F, Lehn N, Lind T, Bayerdorffer E, O'Morain C, Spiller R, et al. Antimicrobial susceptibility testing of Helicobacter pylori in a large multicenter trial: the MACH 2 study. Antimicrob Agents Chemother. 1999; 43:2747–52.
21. Piccolomini R, Di Bonaventura G, Catamo G, Carbone F, Neri M. Comparative evaluation of the E test, agar dilution, and broth micro-dilution for testing susceptibilities of Helicobacter pylori strains to 20 antimicrobial agents. J Clin Microbiol. 1997; 35:1842–6.
22. Gisbert JP, Pajares JM. Stool antigen test for the diagnosis of Helicobacter pylori infection: a systematic review. Helicobacter. 2004; 9:347–68.
23. Vaira D, Malfertheiner P, Megraud F, Axon AT, Deltenre M, Gasbarrini G, et al. Noninvasive antigen-based assay for assessing Helicobacter pylori eradication: a European multicenter study. The European Helicobacter pylori HpSA Study Group. Am J Gastroenterol. 2000; 95:925–9.
24. Toracchio S, Cellini L, Di Campli E, Cappello G, Malatesta MG, Ferri A, et al. Role of antimicrobial susceptibility testing on efficacy of triple therapy in Helicobacter pylori eradication. Aliment Pharmacol Ther. 2000; 14:1639–43.
25. Romano M, Marmo R, Cuomo A, De Simone T, Mucherino C, Iovene MR, et al. Pretreatment antimicrobial susceptibility testing is cost saving in the eradication of Helicobacter pylori. Clin Gastroenterol Hepatol. 2003; 1:273–8.
26. Houben MH, van de Beek D, Hensen EF, Craen AJ, Rauws EA, Tytgat GN. A systematic review of Helicobacter pylori eradication therapy-the impact of antimicrobial resistance on eradication rates. Aliment Pharmacol Ther. 1999; 13:1047–55.
27. van der Wouden EJ, Thijs JC, van Zwet AA, Sluiter WJ, Kleibeuker JH. The influence of in vitro nitroimidazole resistance on the efficacy of nitroimidazole-containing anti-Helicobacter pylori regimens: a meta-analysis. Am J Gastroenterol. 1999; 94:1751–9.
28. Wong BC, Wang WH, Berg DE, Fung FM, Wong KW, Wong WM, et al. High prevalence of mixed infections by Helicobacter pylori in Hong Kong: metronidazole sensitivity and overall genotype. Aliment Pharmacol Ther. 2001; 15:493–503.
29. Glupczynski Y. Antimicrobial resistance in Helicobacter pylori: a global overview. Acta Gastroenterol Belg. 1998; 61:357–66.
30. Glupczynski Y, Megraud F, Lopez-Brea M, Andersen LP. European multicentre survey of in vitro antimicrobial resistance in Helicobacter pylori. Eur J Clin Microbiol Infect Dis. 2001; 20:820–3.
31. Megraud F. Antibiotic resistance in Helicobacter pylori infection. Br Med Bull. 1998; 54:207–16.
32. Kim JM, Kim JS, Jung HC, Kim N, Kim YJ, Song IS. Distribution of antibiotic MICs for Helicobacter pylori strains over a 16-year period in patients from Seoul, South Korea. Antimicrob Agents Chemother. 2004; 48:4843–7.
33. Hachem CY, Clarridge JE, Reddy R, Flamm R, Evans DG, Tanaka SK, et al. Antimicrobial susceptibility testing of Helicobacter pylori. Comparison of E-test, broth microdilution, and disk diffusion for ampicillin, clarithromycin, and metronidazole. Diagn Microbiol Infect Dis. 1996; 24:37–41.
34. Kang JO, Han D, Choi TY. Evaluation of four methods for antimicrobial susceptibility testing of Helicobacter pylori in routine practice. Korean J Clin Microbiol. 2005; 8:82–9.

Table 1.
Interpretative standard for antimicrobial susceptibility testing
Antimicrobials Method Resistance*
Amoxicillin 10 μg disk <25 mm
Clarithromycin 15 μg disk <21 mm
Metronidazole Etest >8 μg/mL
Tetracycline Etest >16 μg/mL

* References[19–21].

Table 2.
Susceptibility of 93 clinical isolates of H. pylori against clarithromycin and metronidazole
Antimicrobial susceptibility N of isolates (%)
C-S/M-S 51 (54.8)
C-S/M-R 26 (28.0)
C-R/M-S 11 (11.8)
C-R/M-R 5 (5.4)
Total 93 (100.0)

Abbreviations: C-S, clarithromycin-sensitive; C-R, clarithromycin-resistant; M-S, metronidazole sensitive; M-R, metronidazole-resistant.

Table 3.
Treatment regimens and clinical outcome
Antimicrobial susceptibility N of patients treated with/N of bacteriologic follow-up /N of patients cured
Total
PAC PBMT PACM PAM PBMTA
C-S/M-S 34/19/18   1/0/-     35/19/18
C-S/M-R 18/12/10     1/1/0   19/13/10
C-R/M-S 3/2/0 4/2/2       7/4/2
C-R/M-R   2/2/1 1/1/0   1/1/1 4/4/2
Total 55/33/28 6/4/3 2/1/0 1/1/0 1/1/1 65/40/32

Abbreviations: C-S, clarithromycin-sensitive; C-R, clarithromycin-resistant; M-S, metronidazole sensitive; M-R, metronidazole-resistant; P, proton pump inhibitor; A, amoxicillin; C, clarithromycin; B, bismuth; M, metronidazole; T, tetracycline.

TOOLS
Similar articles