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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.    Electronic supplementary material  The online version of this article (10.1186/s13756-019-0482-x) contains supplementary material, which is available to authorized users.

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