Surveillance of Helicobacter pylori Antibiotic Susceptibility in Indonesia: Different Resistance Types among Regions and with Novel Genetic Mutations

Abstract

Information regarding Helicobacter pylori antibiotic resistance in Indonesia was previously inadequate. We assessed antibiotic susceptibility for H. pylori in Indonesia, and determined the association between virulence genes or genetic mutations and antibiotic resistance. We recruited 849 dyspeptic patients who underwent endoscopy in 11 cities in Indonesia. E-test was used to determine the minimum inhibitory concentration of five antibiotics. PCR-based sequencing assessed mutations in 23S rRNA, rdxA, gyrA, gyrB, and virulence genes. Next generation sequencing was used to obtain full-length sequences of 23S rRNA, infB, and rpl22. We cultured 77 strains and identified 9.1% with clarithromycin resistance. Low prevalence was also found for amoxicillin and tetracycline resistance (5.2% and 2.6%, respectively). In contrast, high resistance rates to metronidazole (46.7%) and levofloxacin (31.2%) were demonstrated. Strains isolated from Sumatera Island had significantly higher metronidazole resistance than those from other locations. Metronidazole resistant strains had highly distributed rdxA amino acid substitutions and the 23S rRNA A2143G mutation was associated with clarithromycin resistance (42.9%). However, one strain with the highest MIC value had a novel mutation in rpl22 without an A2143G mutation. Mutation at Asn-87 and/or Asp-91 of gyrA was associated with levofloxacin-resistance and was related to gyrB mutations. In conclusions, although this is a pilot study for a larger survey, our current data show that Indonesian strains had the high prevalence of metronidazole and levofloxacin resistance with low prevalence of clarithromycin, amoxicillin, and tetracycline resistance. Nevertheless, clarithromycin- or metronidazole-based triple therapy should be administered with caution in some regions of Indonesia.

Molecular detection of H. pylori antibiotic‐resistant genes and molecular docking analysis

“…These two sites may be related to LVX resistance. 3 However, we found D481E and R484K were present both in antibiotic-resistant and susceptible strains without increasing MIC level of H. pylori resistance to LVX. Seck et al also found no gyrA mutation in some LVX-resistant strains, 34 suggesting other resistance-related mechanisms such as efflux pump, 35 membrane permeability, autophagy, globular transformation, and even new resistant genes.…”

“…1 Currently, the drugs used for H. pylori eradication are mainly composed of proton pump inhibitors and gastric mucosal protectant in combination with one or two kinds of antibiotics, including clarithromycin (CAM), metronidazole (MNZ), levofloxacin (LVX), and amoxicillin. 3,4 However, a research in Brazil showed the resistance mutation was mainly located in A2147G. 2 At present, bacterial factors are regarded as the main cause for antibiotic resistance.…”

Seroprevalence of Helicobacter pylori and Chlamydia pneumoniae among Patients with Coronary Artery Diseases at Mansoura University Hospital, Egypt

“…Other pathogen that may be associated with CAD is H. pylori which is a common pathogen affecting up to 90% of adults worldwide (Malfertheiner et al, 2007;Miftahussurur et al, 2016;Bayındır Bilman et al, 2016;Malfertheiner et al, 2017). It is associated with gastroduodenal disorders like gastritis, duodenal ulcer and gastric adenocarcinoma.…”

Antibiotic self‐medication among non‐medical practitioners in Cirebon city, Indonesia

“…However, the use of antibiotics without indication will speed up the process. It was estimated that Indonesia is one of the countries with high rates of antibiotic resistance even though the data were not connected in a national network …”