Comparison of Epsilometer test and agar dilution method in detecting the sensitivity of Helicobacter pylori to metronidazole

  • Xue-li TIAN ,
  • Zhi-qiang SONG ,
  • Bao-jun SUO ,
  • Li-ya ZHOU ,
  • Cai-ling LI ,
  • Yu-xin ZHANG
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  • Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China

Received date: 2021-07-01

  Online published: 2023-10-09

Supported by

the National Natural Science Foundation of China(81670605);the Clinical Key Projects of Peking University Third Hospital(BYSY2018008)

Abstract

Objective: Agar dilution method (ADM) was used as the golden standard to evaluate the consistency of Epsilometer test (E-test) in detecting the sensitivity of Helicobacter pylori (H. pylori) to metronidazole. Methods: From August 2018 to July 2020, patients with H. pylori infection treated for the first time in Peking University Third Hospital for gastroscopy due to dyspepsia were included in this study. Gastric mucosas were taken from the patients with H. pylori infection. H. pylori culture was performed. Both the ADM and E-test were applied to the antibiotic susceptibility of H. pylori to metro-nidazole, and the consistency and correlation between the two methods were validated. Results: In the study, 105 clinical isolates of H. pylori were successfully cultured, and the minimum inhibitory concentration ≥ 8 mg/L was defined as drug resistance. Both ADM and the E-test showed high resistance rates to metronidazole, 64.8% and 62.9%, respectively. Among them, 66 drug-resistant strains were detected by ADM and E-test, and 37 were sensitive strains, so the consistency rate was 98.1%. Two strains were evaluated as drug resistance by ADM, but sensitive by the E-test, with a very major error rate of 1.9%. There was zero strain sensitive according to ADM but assessed as resistant by the E-test, so the major error rate was 0%. Taking ADM as the gold standard, the sensitivity of E-test in the detection of metronidazole susceptibility was 97.1% (95%CI: 0.888-0.995), and the specificity was 100% (95%CI: 0.883-1.000). Cohen's kappa analysis showed substantial agreement, and kappa coefficient was 0.959 (95%CI: 0.902-1.016, P < 0.001). Spearmans correlation analysis confirmed this correlation was significant (r=0.807, P < 0.001). The consistency evaluation of Bland-Altman method indicated that it was good, and there was no measured value outside the consistency interval. In this study, cost analysis, including materials and labor, showed a 32.2% higher cost per analyte for ADM as compared with the E-test (356.6 yuan vs. 269.8 yuan). Conclusion: The susceptibility test of H. pylori to metronidazole by E-test presents better agreement with ADM. Because it is less expensive, less labor intensive, and more rapid, it is an easy and reliable method for H. pylori susceptibility testing.

Cite this article

Xue-li TIAN , Zhi-qiang SONG , Bao-jun SUO , Li-ya ZHOU , Cai-ling LI , Yu-xin ZHANG . Comparison of Epsilometer test and agar dilution method in detecting the sensitivity of Helicobacter pylori to metronidazole[J]. Journal of Peking University(Health Sciences), 2023 , 55(5) : 934 -938 . DOI: 10.19723/j.issn.1671-167X.2023.05.024

References

1 Sugano K , Tack J , Kuipers EJ , et al. Kyoto global consensus report on Helicobacter pylori gastritis[J]. Gut, 2015, 64 (9): 1353- 1367.
2 Malfertheiner P , Megraud F , OMorain CA , et al. Management of Helicobacter pylori infection: the Maastricht V/Florence consensus report[J]. Gut, 2017, 66 (1): 6- 30.
3 Hu Y , Zhu Y , Lu NH . Primary antibiotic resistance of Helicobac-ter pylori in China[J]. Dig Dis Sci, 2017, 62 (5): 1146- 1154.
4 FitzGerald R, Smith SM. An overview of Helicobacter pylori infection [M]// Methods in Molecular Biology. New York: Humana Press, 2021: 1-14.
5 Thung I , Aramin H , Vavinskaya V , et al. Review article: The global emergence of Helicobacter pylori antibiotic resistance[J]. Aliment Pharmacol Ther, 2016, 43 (4): 514- 533.
6 Pan J , Shi Z , Lin D , et al. Is tailored therapy based on antibiotic susceptibility effective? A multicenter, open-label, randomized trial[J]. Front Med, 2020, 14 (1): 43- 50.
7 Alarcon T , Domingo D , Lopez-Brea M . Discrepancies between E-test and agar dilution methods for testing metronidazole susceptibi-lity of Helicobacter pylori[J]. J Clin Microbiol, 1998, 36 (4): 1165- 1166.
8 Hachem CY , Clarridge JE , Reddy R , et al. Antimicrobial susceptibility testing of Helicobacter pylori, comparison of E-test, broth microdilution, and disk diffusion for ampicillin, clarithromycin, and metronidazole[J]. Diagn Microbiol Infect Dis, 1996, 24 (1): 37- 41.
9 Miftahussurur M , Fauzia KA , Nusi IA , et al. E-test versus agar dilution for antibiotic susceptibility testing of Helicobacter pylori: A comparison study[J]. BMC Res Notes, 2020, 13 (1): 22.
10 CL SI . Methods for dilution antimicrobial susceptibility test for bacteria that grow aerobically[M]. 10th ed Wayne: Clinical and Laboratory Standards Institute, 2015: M07.
11 Alarcón T , Urruzuno P , Martínez MJ , et al. Antimicrobial susceptibility of 6 antimicrobial agents in Helicobacter pylori clinical isolates by using EUCAST breakpoints compared with previously used breakpoints[J]. Enferm Infecc Microbiol Clin, 2017, 35 (5): 278- 282.
12 Hooi JKY , Lai WY , Ng WK , et al. Global prevalence of Helicobacter pylori infection: Systematic review and meta-analysis[J]. Gastroenterology, 2017, 153 (2): 420- 429.
13 刘文忠, 谢勇, 陆红, 等. 第五次全国幽门螺杆菌感染处理共识报告[J]. 中华内科杂志, 2017, 56 (7): 532- 545.
14 Mégraud F , Lehn N , Lind T , et al. Antimicrobial susceptibility testing of Helicobacter pylori in a large multicenter trial: The MACH2 study[J]. Antimicrob Agents Chemother, 1999, 43 (11): 2747- 2752.
15 Glupczynski Y , Broutet N , Cantagrel A , et al. Comparison of the E-test and agar dilution method for antimicrobial suceptibility testing of Helicobacter pylori[J]. Eur J Clin Microbiol Infect Dis, 2002, 21 (7): 549- 552.
16 Osato MS , Reddy R , Reddy SG , et al. Comparison of the E-test and the NCCLS-approved agar dilution method to detect metro-nidazole and clarithromycin resistant Helicobacter pylori[J]. Int J Antimicrob Agents, 2001, 17 (1): 39- 44.
17 El-Halfawy OM , Valvano MA . Antimicrobial heteroresistance: An emerging field in need of clarity[J]. Clin Microbiol Rev, 2015, 28 (1): 191- 207.
18 Ogata SK , Gales AC , Kawakami E . Antimicrobial susceptibility testing for Helicobacter pylori isolates from Brazilian children and adolescents: Comparing agar dilution, E-test, and disk diffusion[J]. Braz J Microbiol, 2015, 45 (4): 1439- 1448.
19 Best LM , Haldane DJ , Keelan M , et al. Multilaboratory comparison of proficiencies in susceptibility testing of Helicobacter pylori and correlation between agar dilution and E-test methods[J]. Antimicrob Agents Chemother, 2003, 47 (10): 3138- 3144.
20 Valdivieso-García A , Imgrund R , Deckert A , et al. Cost analysis and antimicrobial susceptibility testing comparing the E-test and the agar dilution method in Campylobacter jejuni and Campylobacter coli[J]. Diagn Microbiol Infect Dis, 2009, 65 (2): 168- 174.
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