Biological Polymorphisms of Helicobacter pylori on Drug-Susceptibility Test in Clinical Laboratory

Letter to Editor

The drug-susceptibility test is necessary and important examination to perform effective antibiotic therapy for individual infectious disorders irrespective to acute and chronic infections. The methodology for drug-susceptibility test in clinical laboratory crucially contributes to select the effective antibiotics in the regimen. Routinely, a strain of the microorganisms causing the infectious disease is subjected to the drug-susceptibility test in clinical laboratory according to application of health issuance and cost-performance. However, the treatment with the antibiotics chose based on the drug-susceptibility test provides not always successful outcome. Concerning with the importance of the problem, we generally accept the bacteria and host-related factors as follows; minor antibiotic resistant which is not detected and poor adherence and individual pharmacokinetics/dynamics in the body.

One of the chronic infectious disorders, the persistent Helicobacter pylori infection in the human stomach causes to various manifestations of gastro and extra-gastric disorders as reviewed [1,2]. H. pylori is acquired in childhood and the stable colonization continues lifelong unless treated successfully [3]. H. pylori possesses a high genetic diversity/rearrangement, and is persistently colonizing in the stomach due to adapt to the microenvironment of stomach according to the change in the circumstances. The persistent H. pylori infection has been made possible by the coexistence of a variety of strains consisting with newborn mutant strains as a flexible H. pylori community (H. pylori flora) in individual stomachs, leading to biological polymorphism of H. pylori in the stomach [4,5]. Nowadays, the eradication therapy is performed worldwide, however, the eradication failure with antibiotics based on the drug-susceptibility test using a strain is increasing and is worthy of note. Thus, many scientists and medical practitioner are struggling to develop the best regimen for treatment of H. pylori infection. They are investigating to figure out more effective combination therapy with antibiotics and gastric acid secretion inhibitors via the randomized clinical trials [6]. Simultaneously the drug-susceptibility test before antimicrobial prescription should be performed with due consideration for the characteristics of the examinations and bacterial features. The difference of drug-susceptibility tests e.g. E-test and agar dilution sometimes differs the values of Minimum Inhibitory Concentration (MIC) [7,8]. Furthermore, in particularly, H. pylori utilizes the high proper adaptation strategies mentioned above and survives as H. pylori flora in the stomach [4,5], which probably affects the results of the drug-susceptibility test. In the fact, in the case of eradication failure, the discrepancy between the result from the drug-susceptibility test and clinical outcome is reported [6,9-11]. When a single strain is used in the examination, it is hard to provide the accurate result/ MIC value for the effective antibiotic therapy. Thus, we are analyzing with at least each 10 strain from individual patients to clarify the biological polymorphism of H. pylori on the drug-susceptibility. Four antibiotics such as clarithromycin, amoxicillin, metronidazole and sitafloxacin, were used in the drug-susceptibility test. So far, the diversity of MIC value among the multiple strains in the stomach is confirmed by the drug-susceptibility test in clinical laboratory. Interestingly, antibiotic-sensitive and -resistant strains coexisted even in a stomach. Moreover, the MIC values differ among the resistant strains in a stomach. These results seem to relate with the anatomical site where H. pylori exists and the history of antibiotic therapy. We need more investigations with the increased cases including primary treatment and eradication failure to clarify the effect of such biological polymorphism of H. pylori on the drug-susceptibility.

References

1. Wang F, Meng W, Wang B, Qiao L. Helicobacter pylori-Induced Gastric Inflammation and Gastric Cancer. Cancer Lett. 2014; 345: 196-202.
2. Tsay FW, Hsu PI. pylori Infection and Extra-Gastroduodenal Diseases. J Biomed Sci. 2018; 25: 65.
3. Talebi Bezmin Abadi A. Therapy of Helicobacter pylori: Present Medley and Future Prospective. Bio Med Res Int. 2014; 124607.
4. Takeuchi H, Zhang Y, Israel DA, Peek Jr. RM, Kamioka M, Yanai H, et al. Effect of Helicobacter pylori cdrA on Interleukin-8 Secretions and Nuclear Factor Kappa B Activation. World J Gastroenterol. 2012; 18: 425-434.
5. Takeuchi H, Kira M, Konishi S, Uchiyama J, Matsuzaki S, Matsumura Y. Polymorphisms in The Helicobacter pylori NY43 Strain and Its Prophage-cured Derivatives. Microbiology. 2018; 164: 877-882.
6. Talebi Bezmin Abadi A, Yamaoka Y. Helicobacter pylori Therapy and Clinical Perspective. J Glob Antimicrob Resist. 2018; 14: 111-117.
7. Hachem CY, Clarridge JE, Reddy R, Flamm R, Evans DG, Tanaka K, 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.
8. Van der Wouden EJ, De Jong A, Thijs JC, Kleibeuker JH, Van Zwet AA. Subpopulations of Helicobacter pylori Are Responsible for Discrepancies in the Outcome of Nitroimidazole Susceptibility Testing. Antimicrob Agents Chemother. 1999; 43: 1484-1486.
9. Blümel B, Goelz H, Kist M, Glocker EO. Retrospective Study on Outcome of Salvage Helicobacter pylori Eradication Therapies Based on Molecular Genetic Susceptibility Testing. Helicobacter. 2018; 23: e12494.
10. Arslan N, Yilmaz Ö, Demiray-Gürbüz E. Importance of Antimicrobial Susceptibility Testing for The Management of Eradication in Helicobacter pylori World J Gastroenterol. 2017; 23: 2854-2869.
11. Thung I, Aramin H, Vavinskaya V, Gupta S, Park JY, Crowe SE, et al. Review Article: The Global Emergence of Helicobacter pylori Antibiotic Resistance. Aliment Pharmacol Ther. 2016; 43: 514-533.