Alternative eradication regimens for Helicobacter pylori infection in Indonesian regions with high metronidazole and levofloxacin resistance

Background: The prevalence of Helicobacter pylori resistance to metronidazole and clarithro-
mycin is high in Indonesia. Moreover, the increasing levofloxacin resistance rates in the absence
of bismuth treatment in Indonesia has led to the use of other antibiotics as alternative regimens.
Methods: We determined the minimum inhibitory concentrations (MICs) of five alternative
antibiotics for H. pylori (rifaximin, rifabutin, furazolidone, garenoxacin, and sitafloxacin) using
the agar dilution method and assessed mutations associated with antibiotic resistance using
next-generation sequencing.
Result: Analysis of 106 strains isolated from 1039 adult dyspeptic patients revealed that
none of the strains were furazolidone-resistant. All strains were also sensitive to rifabutin and
sitafloxacin. In contrast, the rates of resistance to rifaximin and garenoxacin were high (38.9%
and 6.7%, respectively). The strains isolated from patients on Java Island had the highest
resistance rates to garenoxacin and rifaximin. In addition, the resistance was distributed evenly
among the ethnic groups, ranging between 25.0% and 69.2%. Except for rifaximin, for which
the resistance rate was 38.9%, the other four antibiotics could be successfully employed to
eradicate levofloxacin- and metronidazole-resistant H. pylori infections in vitro. Interestingly,
garenoxacin-sensitive strains were found in regions with high clarithromycin resistance rates
such as Bali and Papua Islands. In contrast, rifaximin might not be considered as an alternative
antibiotic in regions with high clarithromycin resistance. There was an inconsistent association
between gyrA and gyrB mutations and garenoxacin resistance. We confirmed that the I837V
(replacement of isoleucine at position 837 with valine), A2414T/V, Q2079K and K2068R were
the predominant rpoB point mutations. There was an association between vacA genotypes of
H. pylori and rifaximin resistance (P = 0.048).
Conclusion: furazolidone-, rifabutin-, and sitafloxacin-based therapies might be considered as
alternative regimens to eradicate H. pylori in Indonesia, including regions with high metroni-
dazole and clarithromycin resistance rates. Moreover, sitafloxacin but not garenoxacin should
be considered for eradication of levofloxacin-resistant strains.