First-Line Treatment in the Eradication of
Helicobacter Pylori: where are we now?
Fatih Ciftci1* and Turgut Anuk2
1Istanbul Gelisim University, Turkey
2Kafkas University, Turkey
Submission: December 13, 2016; Published: January 23, 2017
*Corresponding author: Fatih Ciftci, Istanbul Gelisim University, Vocational School of Health Services, Basakmah, Bulvar İstanbul sitesi E-4/79 34306, Basaksehir/Istanbul-Turkey, Tel:+905056164248;Fax:+902124627056; Email; firstname.lastname@example.org
How to cite this article: Fatih C, Turgut A. First-Line Treatment in the Eradication of Helicobacter Pylori: where are we now?. Adv Res Gastroentero Hepatol 2017; 2(4): 555594. DOI: 10.19080/ARGH.2017.02.555594
Aim: Helicobacter pylori (HP) are the most common human infectious agent worldwide. Approximately half of the patients remain infected after ‘eradication’ treatment with the triple regimen of a proton pump inhibitor (PPI), amoxicillin (AMO), and clarithromycin (CLA). In this study, this PPI-based triple regimen was compared to a quadruple regimen, including bismuth citrate (BC), a PPI, metronidazole (MET), and tetracycline (TET), and BPMT.
Methods: Total 215 patients who were treated with lansoprozole (LAN), AMO and CLA (LAC); and another 210 patients who were treated with BPMT for 14 days for the purpose of HP eradication between January 2011 and April 2014 were included in this study. The treatment period was 14 days for both groups.
Results: Demographic characteristics and endoscopic findings were similar in both groups. The HP eradication rate was % 53.4 in the LAC group, and it was %78.5 in the BPMT group (P< 0.05). The rates of non-compliance with treatment and side effects were higher in the BPMT group (P< 0.05). Among all, 55 patients in the LAC group and 110 patients in the BPMT group were reported to have had difficulties conforming to the treatment (P = 0.020). In the questionnaire on the side effects of the drugs, 30 patients in the LAC group and 90 in the BPMT group gave positive answers (P = 0.006). The most frequently reported side effects were dry mouth and metallic taste. The eradication rates were % 53.4 in the LAC regimen, and %78.5 in the BPMT regimen. This difference was statistically significant (P = 0.026).
Conclusion: The efficacy of LAC for HP eradication in Turkey has diminished due to high microbial resistance to antibiotics. The BPMT regimen should be considered a first-line treatment because of its higher eradication rate. We suggest that BPMT could be accepted as a first-line treatment for acute HP infection. LAC is an alternative treatment for a select group of patients.
Helicobacter pylori (HP) are the most common human infectious agent worldwide . In some countries the prevalence is up to 85-90% . It plays a role in the aetiology of many gastric disorders including adenocarcinoma, and is associated with some haematological, neurological, and cardiovascular conditions [3-7]. Since the discovery of HP, the triple regimen treatment has been used as the standard approach for its eradication. This consists of a PPI and two antibiotics, usually AMO and CLA [1,5,7-29]. In recent years other antibiotics have also been used [30,31]. Because of the development of microbial resistance to CLA worldwide, more attention has been paid to alternative therapies. Thus, a BC-containing quadruple regime has been widely used in recent years [1,4,5,7,15,17,19,21,25,27,32-40]. Recent studies cARGHied out in our country have indicated that microbial resistance to CLA has risen beyond %50, rendering the success of the classical triple regimen unacceptably poor [3,16,20,26,28,41,42].
Given all of these studies, alternatives to the standard PPI regimen have drawn the attention of clinicians. In our clinic, HP eradication treatment now consists of a 14-day course of oral tablets, consisting of a BC 600 mg tablet BID, a PPI (OME 200 mg or LAN 30 mg) capsule BID, an MET 500 mg tablet TID, and a TET 500 mg tablet QID. This is the quadruple BPMT regimen. Our previous approach used to be the triple regimen of a LAN 30 mg capsule BID, an AMO 1000 mg tablet BID, and a CLA 500
mg tablet BID. In the present study, we compared these two
commonly applied first-line treatments to the eradication of HP.
In our country, there are endoscopy units in most general
surgery hospitals. HP is the most common infection throughout
the world and has been shown to be associated with gastric
cancer. Thus, data concerning HP eradication are a matter of
concern not for only for medical gastroenterologists but also for
Total 425 patients who underwent endoscopic biopsies and
were found to have HP infection received 14-day treatments for
HP eradication. Following the treatment, a second endoscopy
and a urea breath test (Heliprobe, Noster AB, Sweden) or an HP
stool antigen test (Antigen card test, Dialab, Austria) were done
to evaluate the rate of eradication. The patients were divided
into two groups: group l (LAC) and group II (BPMT). The patients
were randomised into LAC and BPMT groups with a computergenerated
random number. The patients were evaluated for
eradication rate, difficulty in conforming to the treatment, and
drug side effects. Smoking habits, alcohol consumption, and
use of other drugs were also recorded. Reports of pathological
examinations were scrutinised for the presence of precancerous
lesions and these results were also recorded. All study
participants, or their legal guardian, provided written informed
consent prior to study enrolment.
There were 215 patients in the ‘classical’ LAC group and 210
in the BPMT group. Patient demographic characteristics, comorbidities,
smoking habits, alcohol consumption habits, and
use of other drugs were similar between the groups (P > 0.05)
(Table 1). There were also no significant differences between the
groups in terms of endoscopic biopsy findings (P> 0.05) (Table
In all, 55 patients in group 1 and 110 patients in group II
reported difficulties in conforming to the treatments (P = 0.020).
In the questionnaire for drug side effects, 30 patients in group
I and 90 in group II reported positive answers (P = 0.006).
The most frequently reported side effects were dry mouth and
metallic taste. Evaluating eradication rates, the LAC regimen was
% 53.4successful and the BPMT regimen was %78.5 successful.
This difference was statistically significant (P = 0.026) (Table 3).
LAC: Lansoprazole Amoxicillin and Clarithromycin Triple Regimen;
BPMT: Bismuth Citrate Proton Pump Inhibitor Metronidazde and
Tetracycline Quadruple Regimen.
HP is a Gram-negative spiral bacteria and the most common
infectious agent worldwide. It is estimated that about half of
the global population is infected. It is an important factor in the
aetiology of gastritis, gastric and duodenal ulcers, gastric mucosaassociated
lymphoma (MALT), and gastric adenocarcinoma [3-6].
Recent studies have shown that HP infection is also associated
with some diseases outside the gastrointestinal system, including
refractory iron deficiency anaemia, idiopathic thrombocytopenic
purpura (haematological system) paralysis, Parkinson’s disease,
Alzheimer’s disease (neurological system), and ischemic heart
disease (cardiovascular system) .
Since the discovery of HP in 1983, diagnostic and therapeutic
approaches to gastritis and peptic ulcers have changed greatly
. In 1994, the World Health Organization International
Agency for Research on Cancer reached the conclusion that HP
has a causative relationship with gastric carcinogenesis and
that the agent is a definite carcinogen in humans . Since
then, much more attention has been focused on this agent. In
the Mongolian gerbil model, it was shown that HP could induce
gastric cancer independent of exposure to low-dose chemical
carcinogens . In the early 2000s, survey studies cARGHied
out in Japan showed that HP infection increased the risks of
intestinal metaplasia and diffuse-type gastric cancer [29,45].
The estimated risk of developing cancer attributable to HP varies
between%50 and %73(46). In a randomised study cARGHied out in
Colombia that included patients with high-risk and precancerous
lesions, it was observed that there was a significant decrease
in cancer rate among those who had HP eradicated . In
another randomised study cARGHied out in China, HP eradication
significantly decreased the risk of gastric cancer in individuals
without gastric atrophy and intestinal metaplasia or dysplasia
. The benefit of HP eradication on gastric cancer has been a
subject in other studies too. A study in Japan showed that gastric
cancer risk in the residual stomach after distal gastrectomy and
Billroth I anastomosis for previous gastric cancer decreased
significantly subsequent to HP eradication .
Currently, various treatment protocols are being used for the
eradication of HP. It was reported that prior to the 2000s, the
triple regimen was successful at a rate of ~%95 . However,
with the development of microbial resistance to CLA, this
success rate has decreased to %55 22. Thus, there has recently
been a trend towards the quadruple regimen including BC, which
has anti-HP and mucosal cytoprotective effects. For this reason,
it is expected that protocols including BC will be effective .
Indeed, some studies have shown this regimen to be effective
In this study, we compared the most commonly used firstline
treatment protocols. The choice of OME or LAN as the PPI in
BPMT depends on the clinician’s preference. However, a previous
study reported no significant differences between various PPIs in
terms of efficacy . In the present study, a second endoscopic
examination, and a urea breath test or HP stool antigen test
was done at least 8 weeks after treatment to evaluate the rate
of eradication. Other studies have shown that these tests have
the same value and their sensitivities and specificities exceed
%90 [51-54]. The use of different PPI drugs did not seem to have
affected our results.
There were no significant differences between our patient
groups in terms of their general characteristics and endoscopic
biopsy findings. However, the rate of difficulty in conforming
to treatment and side effects were higher in the BPMT group.
This could be due the high number of tablets prescribed (13
tablets daily) and the high doses. Indeed, other studies have
also referred to difficulties in the use of the BPMT protocol .
Patients are advised to take the drugs after meals and to drink a
lot of water to minimise the side effects of the antibiotics. Other
studies have proposed the use of probiotics to minimise the side
effects of antibiotics and increase eradication [7,15].
Evaluation of the eradication rates in our study showed a
%78.5 success rate in the BPMT group and % 53.4success in the
This difference was statistically significant. The low success
rate in the LAC group is consistent with the results of other
studies cARGHied out in our country and is attributed to increased
microbial resistance to CLA [16,20,42]. A meta-analysis in our
country showed that the success rate of the triple regimen was
%79.4 in 1996 and decreased to %61.1 in 2005 . In recent
years, this rate has been estimated to be % 50-55 . Although
the success rate with BPMT was higher (%78.5) than that with
LAC, this rate was well below expectations. The reason for this
could be the growing resistance to MET in our country and
Other treatment approaches should be considered for cases
where eradication is unsuccessful. Currently, various alternative
regimens are being used. These include successive, combination,
hybrid, and rescue regimens, some of which include the use of
levofloxacin and the classical anti-tuberculosis agent rifabutin
[7,15]. Limitations of our study included patient’s not completing
follow-up, reporting too late for re-evaluation, and insufficient
information being obtained from the patients.
A 14-day treatment with the BPMT regimen was more
successful than the classical LAC regimen for HP eradication. In
some patients, drug side effects and difficulty conforming to the
treatment were a problem. In cases of unsuccessful eradication,
other regimens described in the literature should also be