Effective therapeutic regimens in two South Asian countries with high resistance to major Helicobacter pylori antibiotics

Antimicrob Resist Infect Control. 2019 Feb 15:8:40. doi: 10.1186/s13756-019-0482-x. eCollection 2019.

Abstract

Background: Nepal and Bangladesh have a high prevalence of Helicobacter pylori with high resistance rates to clarithromycin, metronidazole, and levofloxacin. Here, we evaluated the susceptibility and genetic mutations of 5 alternative antibiotics against isolates from both countries to obtain an effective treatment regimen for H. pylori eradication.

Methods: We used the agar dilution method to determine the minimal inhibitory concentration of 5 alternative antibiotics against 42 strains from Nepal and 56 from Bangladesh and performed whole genome mutation analysis.

Results: No resistance to furazolidone or rifabutin and a high susceptibility of sitafloxacin (95.2% in Nepal and 98.2% in Bangladesh) were observed. In contrast, resistance to rifaximin (52.4% in Nepal and 64.3% in Bangladesh) was high. Moreover, resistance to garenoxacin was higher in Bangladesh (51.6%) than in Nepal (28.6%, P = 0.041), most likely due to its correlation with levofloxacin resistance (P = 0.03). Garenoxacin and rifaximin were significantly correlated in Bangladesh (P = 0.014) and occurred together with all sitafloxacin-resistant strains. Mutations of gyrA could play a significant role in garenoxacin resistance, and double mutations of A87 and D91 were associated with sitafloxacin resistance. Analysis of the rpoB gene demonstrated well-known mutations, such as V657I, and several novel mutations, including I2619V, V2592 L, T2537A, and F2538 L.

Conclusions: Rifabutin can be cautiously implemented as therapy for H. pylori infection due to its interaction with the tuberculosis endemic in Bangladesh. The high susceptibility of furazolidone and sitafloxacin suggests their possible future application in Nepal and Bangladesh.

Keywords: Antibiotics; Bangladesh; Drug resistance; Helicobacter pylori; Nepal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bangladesh
  • DNA Gyrase / genetics
  • DNA, Bacterial / genetics
  • DNA-Directed RNA Polymerases / genetics
  • Drug Resistance, Bacterial*
  • Female
  • Fluoroquinolones / pharmacology
  • Fluoroquinolones / therapeutic use
  • Furazolidone / pharmacology
  • Furazolidone / therapeutic use
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / isolation & purification
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Mutation*
  • Nepal
  • Rifabutin / pharmacology
  • Rifabutin / therapeutic use
  • Whole Genome Sequencing / methods

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Fluoroquinolones
  • Rifabutin
  • Furazolidone
  • sitafloxacin
  • DNA-Directed RNA Polymerases
  • DNA Gyrase