1. Thung I, Aramin H, Vavinskaya V, et al. Review article: the global
emergence of Helicobacter pylori antibiotic resistance. Aliment Pharma-
col Ther. 2016;43:514-533.
2. Zullo A, Rinaldi V, Winn S, et al. A new highly effective short-term
therapy schedule for Helicobacter pylori eradication. Aliment Pharmacol
3. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guide-
line: treatment of Helicobacter pylori Infection. Am J Gastroenterol.
4. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Heli-
cobacter pylori infection – the Maastricht V/Florence Consensus
Report. Gut. 2017;66:6-30.
5. Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for
the treatment of Helicobacter pylori infection in adults. Gastroenterol-
6. Gatta L, Scarpignato C, Fiorini G, et al. Impact of primary antibiotic resis-
tance on the effectiveness of sequential therapy for Helicobacter pylori
infection: lessons from a 5-year study on a large number of strains. Ali-
ment Pharmacol Ther. 2018;47:1261-1269.
7. Graham DY. Hp-normogram (normo-graham) for assessing the out-
come of H. pylori therapy: effect of resistance, duration, and
CYP2C19 genotype. Helicobacter. 2016;21:85-90.
8. McNicholl AG, Nyssen OP, Bordin DS, et al. Pan-European Registry
on H. pylori Management (Hp-EuReg): bacterial Resistance of 2,241 H.
pylori isolates. Helicobacter. 2017;22:56.
Editorial: Helicobacter pylori resistance and sequential
We are indebted to Drs Siddique and Moss
for their thoughtful edi-
torial and their kind words of appreciation of our work.
Following the discovery of Helicobacter pylori (H. pylori) and its
association with peptic ulcer disease,
the search for effective thera-
pies against the microorganism began. After the early observation of
the efficacy of bismuth compounds, all subsequent regimens (be
they dual, triple, sequential or quadruple) included a proton pump
inhibitor (PPI; Table 1). While drug, dose, formulation and duration
of treatment are all important factors, resistance to antimicrobials as
well as the selected antisecretory regimen remain the most critical
factors influencing the global eradication rate.
Despite being regionally dependent, the prevalence of antimicrobial
resistance is rising worldwide.
As a consequence, the success of H.
pylori therapies is declining globally. We therefore agree with Siddique
on their recommendation of a “wise choice” of eradication
regimens, based on local patterns of resistance. Our work
that a large number of strains need to be assessed to give reliable esti-
mates of the effectiveness of a given eradication regimen in patients
harbouring resistant strains. Unfortunately, however, most studies with
different H. pylori therapies have evaluated numbers of strains that are
well below the “cut-off value,” under which the interpretation (if any) of
the clinical results obtained with a given eradication regimen should be
made with caution. Provided these results are duly reproduced with
other regimens, they will influence future guidelines. Until now, even
the more prestigious recommendations have been issued on the basis
of clinical studies performed on a limited number of patients harbouring
resistant strains. For instance, in the Maastricht V/Florence guidelines,
only 32 patients with strains resistant to both clarithromycin and
metronidazole were evaluated with the non-bismuth concomitant ther-
apy, while our estimates suggest a cut-off of at least 120.
PPIs display several pharmacological actions that give them a place
in eradication regimens. However, the importance of profound and
long-lasting acid suppression for H. pylori eradication is of paramount
importance and is illustrated by studies showing a significantly higher
intragastric pH and lower per cent time spent at pH < 4 in patients with
successful eradication vs those who did not get rid of the bacterium.
Profound suppression of intragastric acidity is therefore needed to
achieve the best eradication rates. Indeed, some studies have shown
that high-dose PPIs might result in high eradication rates even when a
single antimicrobial agent is used.
The recent availability of more
TABLE 1 Helicobacter pylori eradication regimens: a short history
Year Proponent(s) Regimens
1983 Marshall Bi compounds
1987 Borody et al Bi Compounds
1993 Unge and Ekstr
om PPI + Amoxicillin
1993 Bell et al PPI + Amoxicillin
Bazzoli et al PPI + Clarithromycin
1994 Cayla et al PPI + Clarithromycin
1995 Borody et al PPI + Bi + Tetracycline
1998 Treiber et al PPI concomitant therapy
1998 Okada et al
2000 Zullo et al PPI sequential therapy
2011 Hsu et al PPI hybrid therapy
© 2018 John Wiley & Sons Ltd