Molecular characterization and prevalence of antibiotic resistance in Helicobacter pylori isolates in Kuala Lumpur, Malaysia

Abstract

Aims and objectives

Helicobacter pylori has been classified as high priority pathogen by the WHO in 2017. The emergence of antibiotic-resistant strains is one of the main causes of treatment failure in H. pylori infection. This study determined and characterized primary and secondary resistances in H. pylori in Malaysia.

Materials and methods

Gastric biopsies from antrum (n=288) and corpus (n=283) were obtained from 288 patients who underwent endoscopy at Universiti Kebangsaan Malaysia Medical Center (UKMMC), Kuala Lumpur, Malaysia. Antibiotic susceptibility to six classes of antibiotics was determined by the E-test. Mutations conferring in resistance in functional genes were identified by PCR and sequencing.

Results

Overall resistance rates to metronidazole, clarithromycin and levofloxacin were 59.3% (35/59), 35.6% (21/59) and 25.4% (15/59), respectively. Secondary isolates showed significantly higher resistance rates to clarithromycin compared to the primary isolates. Mixed infection with susceptible and resistant isolates was observed in 16.2% (6/37) of cases, of which 83.3% (n=5) had infection with the same strain. 41% (18/44) of isolates were resistant to more than one class of antibiotics of which 50% (9/18) were multidrug-resistant, two being primary and seven being secondary isolates. Mutations in rdxA, 23S rRNA and gyrA genes were associated with resistance to metronidazole, clarithromycin and levofloxacin, respectively.

Conclusion

The high level of resistance to metronidazole, clarithromycin and levofloxacin seen in H. pylori isolates in our setting warrants the need for continuous surveillance and highlights caution in use of antibiotics generally used as first-line therapy in H. pylori eradication regimen.

Keywords:

• Helicobacter pylori
• antibiotic resistance
• clarithromycin
• metronidazole
• levofloxacin
• point mutation

Acknowledgment

We would like to thank the Universiti Kebangsaan Malaysia for providing both the permission and the facilities to conduct and publish this research. The research was funded by a grant from Universiti Kebangsaan Malaysia under Economic Transformation Programme Research Fund Scheme (grant no. ETP-2013-042).

Ethics approval and informed consent

The study was approved by the Medical Research Ethic Committee of the University (UKM 1.5.3.5/244/ETP-2013-042) and written informed consent was obtained from each patient and the study was conducted in accordance with the Declaration of Helsinki.

Data sharing statement

Data will be shared and available from the corresponding author on reasonable request.

Author contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

HB received a scholarship from the Universiti Kebangsaan Malaysia under the postgraduate “Zamalah” program. The authors declare no other conflicts of interest in this work.