Accepted Manuscript Title: Efficacy of triple therapy with esomeprazole, amoxicillin, and sitafloxacin as a third-line Helicobacter pylori eradication regimen Author: Yoshihiro Hirata Takako Serizawa Satoki Shichijo Nobumi Suzuki Kosuke Sakitani Yoku Hayakawa Atsuo Yamada Kazuhiko Koike PII: DOI: Reference:
S1201-9712(16)31146-8 http://dx.doi.org/doi:10.1016/j.ijid.2016.08.019 IJID 2695
To appear in:
International Journal of Infectious Diseases
Received date: Revised date: Accepted date:
20-7-2016 22-8-2016 23-8-2016
Please cite this article as: Hirata Y, Serizawa T, Shichijo S, Suzuki N, Sakitani K, Hayakawa Y, Yamada A, Koike K, Efficacy of triple therapy with esomeprazole, amoxicillin, and sitafloxacin as a third-line Helicobacter pylori eradication regimen, International Journal of Infectious Diseases (2016), http://dx.doi.org/10.1016/j.ijid.2016.08.019 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Highlights
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Third-line H. pylori eradication regimen is not established in Japan.
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Esomeprazole was the latest PPI approved in Japan with superior acid
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suppression. The effect of third-line therapy with esomeprazole and sitafloxacin was examined.
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Esomeprazole and sitafloxacin-based third-line therapy showed 83 % eradication
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rate. Adverse events were comparable to former PPI-based therapies.
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Efficacy of triple therapy with esomeprazole, amoxicillin, and sitafloxacin as a third-line Helicobacter pylori eradication regimen
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11 Yoshihiro Hirata, Takako Serizawa, Satoki Shichijo, Nobumi Suzuki, Kosuke Sakitani,
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Yoku Hayakawa, Atsuo Yamada, Kazuhiko Koike
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Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo,
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113-8655, Tokyo, Japan
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Correspondence to: Yoshihiro Hirata, MD, PhD, Department of Gastroenterology,
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Graduate School of Medicine, the University of Tokyo, 113-8655, 7-3-1, Hongo,
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Bunkyo-ku, Tokyo, Japan.
[email protected]
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Telephone: +81-3-38155411
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Fax: +81-3-58008812
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23 Abstract
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AIM: To examine the efficacy of third-line Helicobacter pylori eradication therapy with
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esomeprazole, amoxicillin, and sitafloxacin for patients with clarithromycin- and
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metronidazole-based first- and second-line therapy failure.
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METHODS: Thirty patients with first- and second-line H. pylori eradication failure
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were prospectively treated with esomeprazole 20 mg twice daily (b.i.d.), amoxicillin 750
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mg b.i.d., and sitafloxacin 100 mg b.i.d. for 7 days. After 8–12 weeks, the outcome of
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eradication therapy was assessed using a 13C-urea breath test or a stool antigen test.
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RESULTS: All 30 patients completed the study. Eradication was successful in 25
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patients and the eradication rate was 83% in the intention-to-treat and per-protocol
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analyses. No specific or significant adverse events were recorded in the 30 patients.
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Patient characteristics such as gender, body mass index, and pepsinogen I/II ratio did
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not differ between patients who were successfully treated and those who were not
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successfully treated.
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CONCLUSION: Third-line H. pylori eradication therapy with esomeprazole, amoxicillin,
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and sitafloxacin is as safe and effective as previously reported sitafloxacin-based triple
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therapy.
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Key words; Helicobacter pylori, third-line eradication, esomeprazole, sitafloxacin
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44 INTRODUCTION
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Chronic Helicobacter pylori (H. pylori) infection causes various gastroduodenal diseases,
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including ulcers and malignancies1-4. Eradication of H. pylori can prevent or cure these
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diseases5-7. In fact, some studies have shown that H. pylori eradication reduces the
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incidence of gastric cancer, suggesting that eradication therapy could be the primary
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therapeutic approach for the upper gastrointestinal diseases8-12.
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Many regimens for H. pylori eradication have been tested since the discovery of this
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bacterium. Generally, a proton pump inhibitor (PPI) and antibiotics are included in an
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eradication regimen to suppress gastric acid and to kill the bacteria. Bacterial
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resistance to specific antibiotics significantly reduces the efficacy of an eradication
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regimen containing the corresponding antibiotics, and resistance is associated with the
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consumption of antibiotics, which is influenced by socioeconomic status and geographic
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area2, 13, 14.
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In Japan, first-line therapy consists of PPI, amoxicillin (AMX) and clarithromycin
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(CLR) for 7 days which results in 60–70% of eradication rate due to widespread
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CLR-resistant H. pylori15. Second-line therapy includes PPI, AMX and metronidazole
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(MNZ), which has an acceptable eradication rate of 90%3. No standard third-line
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therapy has been established, although several regimens have been examined
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prospectively for their efficacy and adverse events14. Candidate third-line antibiotics
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include fluoroquinolones, one of which, sitafloxacin (STX), has shown good in-vitro
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ability to kill H. pylori
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a modest eradication rate of 70–80%17-19. Studies of primary resistance against STX
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have shown that more than 90% of H. pylori strains are susceptible to this antibiotic18-20.
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However, the in vivo eradication rate of the third-line therapy has not exceeded 90% in
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most studies, so there is still room to improve the STX-based third-line eradication
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regimen21.
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Therefore, we conducted a prospective study of the efficacy of a new third-line
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Helicobacter-eradication
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Esomeprazole is a PPI that was approved by the Ministry of Health, Labor and Welfare
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of Japan in 2011. It has excellent gastric acid control compared to former PPIs such as
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lansoprazole or rabeprazole22,
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third-line therapy.
In prospective studies, STX-based triple therapy has shown
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regimen
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containing
esomeprazole,
AMX,
and
STX.
However, its efficacy has not been evaluated in
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77 MATERIALS AND METHODS
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Subjects
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A prospective exploratory study was conducted to evaluate the efficacy of third-line
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Helicobacter eradication therapy (UMIN clinical trials registry ID no. 000007971).
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Adult patients with a peptic ulcer or chronic gastritis in whom CLR-based first-line and
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MNZ-based second-line therapy had failed were invited to join the study. CLR-based
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first-line therapy consists of PPI, AMX (750mg b.i.d.), CLR (200mg or 400mg b.i.d.) for 7
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days. MNZ-based second-line therapy consists of PPI, AMX (750mg b.i.d.), MNZ (50mg
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b.i.d.) for 7 days. Patients with major organ dysfunction or a history of allergy to PPI,
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AMX or STX were excluded. Prior use of esomeprazole was not excluded. Prior use of
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STX for third-line eradication was excluded. Written informed consent was obtained
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from all patients. The study protocol was approved by the Institutional Review Board of
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the University of Tokyo Hospital (approval No P2012006).
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Eradication
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Before beginning third-line eradication therapy, height and weight was recorded, and
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laboratory tests including liver and renal function tests and pepsinogen were performed.
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Patients were assigned to receive esomeprazole 20 mg twice daily (b.i.d.), AMX 750 mg
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b.i.d., and STX 100 mg b.i.d. for 7 days. We applied 7 days treatment duration for this
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study based on previous third-line Helicobacter eradication reports17-19. Compliance and
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adverse events were assessed through interviews. The outcome of eradication therapy
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was assessed using a
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completing the antimicrobial treatment.
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breath test or a stool antigen test 8–12 weeks after
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13C-urea
H. pylori strains and microbiological examination
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In some cases, H. pylori isolates were obtained from biopsy specimens at endoscopy and
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examined for antimicrobial susceptibility. The minimal inhibitory concentrations
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(MICs) for AMX, CLR, MNZ and STX of each strain were determined using agar
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dilution method. GyrA mutation was also examined by direct sequencing as described
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previously18, 24.
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Statistical analysis
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Statistical analyses were performed using the χ2 test, Student’s t-test and Wilcoxon
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rank-sum test as appropriate. A P-value < 0.05 was considered statistically significant.
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111 RESULTS
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From April 2012 to December 2015, we enrolled 30 patients with a history of second-line
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eradication failure. The mean patient age was 51.8 ± 2.5 years, and 15 were men (Table
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1). All 30 patients took the full course of medication and underwent a
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test or a stool antigen test. Successful eradication was achieved in 25 cases, giving a
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83% eradication rate (95% confidence interval; 65-94%) for both intention-to-treat and
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per-protocol analyses.
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Diarrhea was the most common adverse event, and was recorded in five cases (16.7% of
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the study cohort). One patient (3.3%) suffered moderate diarrhea with seven defecations
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over 2 days, but did not require treatment for diarrhea. A moderate skin eruption after
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the therapy (3.3%) and a moderate asthma attack during the therapy (3.3%) were
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observed in one patient each, and both required specific medications. Stomatitis (3.3%)
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and cystitis (3.3%) were recorded in one patient each, but resolved without specific
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treatment.
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In a subgroup analysis, age, sex, gastric diseases, previous third-line therapy, body
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mass index, and the pepsinogen I/II ratio did not differ between patients with successful
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eradication and those with eradication failure (Table 2).
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urea breath
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Table 3 lists the characteristics of the H. pylori strains isolated before and after
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third-line therapy. In case EAS025, the H. pylori strain had relatively high MICs for
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AMX of 1.0 μg/mL and STX of 0.12 μg/mL with the N87K gyrA mutation before the
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therapy, but it was successfully treated with this third-line regimen. Conversely, the H.
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pylori strain with the lowest MICs for AMX and STX was recovered from case EAS022
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after the third-line therapy failed.
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135 DISCUSSION
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Sitafloxacin-based H. pylori eradication therapy is often used in Japan14. As the
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third-line therapy, 70–78% eradication rates were reported in early three prospective
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studies17-19. Furuta et al. conducted a randomized study containing four arms, which
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showed 84–91% eradication25. These third-line therapy regimens with STX used
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rabeprazole or lansoprazole as the PPI. In this study, we examined the efficacy of
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esomeprazole, the latest conventional PPI approved in Japan, for third-line H. pylori
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eradication in combination with AMX and STX. We obtained an eradication rate of 83%,
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and the adverse events were not specific or severe. This efficacy is in line with prior
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STX-based third-line regimens with rabeprazole or lansoprazole. Contrary to our
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expectations, substitution of esomeprazole for rabeprazole or lansoprazole did not
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improve the eradication rate.
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Several studies have compared the efficacy of eradication with different PPIs with the
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aim of improving the eradication regimen. McNicholl et al. performed a meta-analysis of
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randomized control trials of Helicobacter eradication using esomeprazole, and reported
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the superiority of esomeprazole over first generation PPIs26. The varying acid-inhibiting
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potential of PPIs may affect the eradication efficacy. In other cases, different usage of
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CYPs, enzymes that metabolize PPI, as well as its single nucleotide polymorphism may
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affect the results. However, it is not clear whether differences of PPI affect third-line
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eradication therapy.
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In a previous study, we found enhanced bactericidal activity of STX at near-neutral pH18.
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In addition, a low pepsinogen I/II ratio, which indicates advanced atrophy and
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hypochlorhydria clinically, was associated with a high eradication efficacy using STX18.
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Therefore, we hypothesized that STX-based therapy would be beneficial with sufficient
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acid suppression. However, this was not the case with the esomeprazole-based third-line
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therapy evaluated in the present study. In this study, the eradication rate did not reach
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90%, and the pepsinogen I/II ratio did not affect the eradication results. The
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replacement of esomeprazole with vonoprazan, a novel potassium-competing acid
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blocker that has superior gastric acid control over conventional PPIs27, may improve the
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efficacy of STX-based third-line therapy. It is also possible that factors other than acid
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suppression, such as bacterial resistance, are critical to the eradication outcome13, 14.
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A breakpoint for STX has not been established, and studies have used different
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breakpoints of 0.12 and 1.0 μg/mL19,
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eradicated a strain with 0.12 μg/mL MIC of STX, but were unsuccessful with a strain
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with an MIC less than 0.03 μg/mL. In our previous study of rabeprazole, STX and AMX,
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a strain with 0.12 μg/mL MIC of STX was not eradicated, while a strain with 0.24
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μg/mL was treated successfully18. These results indicate the difficulty interpreting in
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vitro MIC testing in terms of the results of current third-line eradication therapy. In
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this study, we isolated H. pylori strains from only two patients among five unsuccessful
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treated cases, because culture was negative in other two patients and endoscopy was
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not performed in another patient. In the two patients with negative culture results,
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13C-urea
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culture test was false negative. More cases are required to determine the breakpoint of
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STX, particularly in third-line therapy.
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When we conducted this study, no study using esomeprazole as third-line therapy with
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STX had been reported. Recently, Mori et al.28 published a randomized study that
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compared AMX with MNZ as third-line therapy in combination with STX. In that study,
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esomeprazole was used as a PPI, giving eradication rates of 81% and 72%, respectively,
As shown in Table 3, we successfully
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with 10 day third-line regimen. Although the study contained an extremely high
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percentage of STX-resistant H. pylori (57% with an MIC > 1.0 μg/mL) compared to other
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third-line studies, the eradication rate in the intention-to-treat analysis was
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comparable to that of our 7-day protocol. Previously, Furuta et al.25 examined the
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efficacy of 1- or 2-week regimens of STX-based third-line therapy and found no
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statistical difference between the different treatment durations. In contrast, recent
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consensus statements developed by the Canadian Association of Gastroenterology and
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the Canadian Helicobacter Study Group strongly recommend duration of 14 days for all
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H. pylori treatments29. Therefore, appropriate durations of third-line eradication
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regimen as well as those of first- and second-line therapy may require re-evaluation in
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Japan.
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In conclusion, third-line H. pylori eradication therapy with esomeprazole gave an 83%
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of eradication rate, which was comparable to previous STX-based third-line therapy.
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This suggests that the substitution of esomeprazole for reported PPIs could be another
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option for third-line H. pylori the eradication therapy.
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Acknowledgements; The authors wish to thank doctors who introduced eligible patients
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with first- and second-line eradication failures to our hospital for this clinical trial.
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202 Fundings; This research did not receive any specific grant from funding agencies in the
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public, commercial, or not-for-profit sectors.
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Competing interest; No conflict of interest to declare.
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Ethical approval; P2012006 by the Institutional Review Board of the University of
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Tokyo Hospital
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210 Table 1. Demographic characteristics of the patients and result of eradication therapy Total
Age (mean ± SE)
51.8 ± 2.5
Sex (male/female)
15/15
Diagnosis (ulcer/gastritis)
15/15
Previous eradication therapy (second/more)
28/2
Body mass index (mean ± SE)
23.7 ± 0.6
Pepsinogen I/II ratio (mean ± SE)
3.4 ± 0.3
Eradication result (success/failure)
25/5
Eradication rate [% (95% CI) (ITT)]
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Table 2. Patients characteristics according to eradication results Patients treated
Patients not treated
successfully (n = 25)
successfully (n = 5)
Age (mean ± SE)
50.8 ± 0.9
56.8 ± 3.5
0.38
Sex (male/female)
14/11
1/4
0.14
Diagnosis (ulcer/gastritis)
13/12
2/3
0.51
Previous eradication therapy (second/more)
23/2
5/0
0.51
Body mass index (mean ± SE)
23.6 ± 0.6
23.9 ± 2.7
0.84
Pepsinogen I/II ratio (mean ± SE)
3.4 ± 0.3
3.4 ± 0.6
0.96
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83% (65-94%)
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Eradication rate [% (95% CI) (PP)]
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p-value
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Table 3. Characteristics of H. pylori strains isolated from patients before or after third-line therapy.
216 Before therapy Results
MIC (μg/mL)
MIC (μg/mL)
gyrA STX
EAS017
N/A
N/A
N/A
N/A
N/A
EAS020
≤ 0.03
32
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≤ 0.03
EAS022
N/A
N/A
N/A
EAS025
1.0
32
32
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AMX
CLR
failed
≤ 0.03
8
wild
successful
N/A
N/A
N/A
failed
0.12
N87K
successful
N/A
gyrA
MNZ
STX
32
0.12
N87K
N/A
N/A
N/A
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≤ 0.03
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≤ 0.03
N87K
N/A
N/A
N/A
N/A
N/A
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After therapy
N/A, not available.
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References:
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1.
Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the
223
development of gastric cancer. N Engl J Med 2001;345:784-9. 2.
225 226
Graham DY. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology 2015;148:719-31 e3.
3.
Asaka M, Kato M, Takahashi S, Fukuda Y, Sugiyama T, Ota H, Uemura N,
cr
224
ip t
222
Murakami K, Satoh K, Sugano K. Guidelines for the management of Helicobacter
228
pylori infection in Japan: 2009 revised edition. Helicobacter 2010;15:1-20.
229
4.
us
227
Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ. Management of
231
Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut
232
2012;61:646-64. 5.
Marshall BJ, Goodwin CS, Warren JR, Murray R, Blincow ED, Blackbourn SJ,
M
233
an
230
234
Phillips M, Waters TE, Sanderson CR. Prospective double-blind trial of duodenal
235
ulcer relapse after eradication of Campylobacter pylori. Lancet 1988;2:1437-42. 6.
Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG.
ed
236 237
Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated
238
lymphoid tissue type after eradication of Helicobacter pylori. Lancet 1993;342:575-7. 7.
Gasbarrini A, Franceschi F, Tartaglione R, Landolfi R, Pola P, Gasbarrini G.
pt
239
Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori.
241
Lancet 1998;352:878.
242
8.
243
You WC, Brown LM, Zhang L, Li JY, Jin ML, Chang YS, Ma JL, Pan KF, Liu WD, Hu Y, Crystal-Mansour S, Pee D, Blot WJ, Fraumeni JF, Jr., Xu GW, Gail MH.
244
Randomized double-blind factorial trial of three treatments to reduce the prevalence
245 246
Ac ce
240
of precancerous gastric lesions. J Natl Cancer Inst 2006;98:974-83.
9.
247
Ogura K, Hirata Y, Yanai A, Shibata W, Ohmae T, Mitsuno Y, Maeda S, Watabe H, Yamaji Y, Okamoto M, Yoshida H, Kawabe T, Omata M. The effect of Helicobacter
248
pylori eradication on reducing the incidence of gastric cancer. J Clin Gastroenterol
249
2008;42:279-83.
250
10.
Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Terao S, Amagai K,
251
Hayashi S, Asaka M. Effect of eradication of Helicobacter pylori on incidence of
252
metachronous gastric carcinoma after endoscopic resection of early gastric cancer:
253
an open-label, randomised controlled trial. Lancet 2008;372:392-7.
16 Page 16 of 18
254
11.
Mabe K, Takahashi M, Oizumi H, Tsukuma H, Shibata A, Fukase K, Matsuda T,
255
Takeda H, Kawata S. Does Helicobacter pylori eradication therapy for peptic ulcer
256
prevent gastric cancer? World J Gastroenterol 2009;15:4290-7.
257
12.
Shichijo S, Hirata Y, Sakitani K, Yamamoto S, Serizawa T, Niikura R, Watabe H, Yoshida S, Yamada A, Yamaji Y, Ushiku T, Fukayama M, Koike K. Distribution of
259
intestinal metaplasia as a predictor of gastric cancer development. J Gastroenterol
260
Hepatol 2015;30:1260-4.
261
13.
ip t
258
Thung I, Aramin H, Vavinskaya V, Gupta S, Park JY, Crowe SE, Valasek MA.
Review article: the global emergence of Helicobacter pylori antibiotic resistance .
263
Aliment Pharmacol Ther 2016;43:514-33. 14.
265 266
Song M, Ang TL. Second and third line treatment options for Helicobacter pylori
us
264
cr
262
eradication. World J Gastroenterol 2014;20:1517-28. 15.
Kawai T, Takahashi S, Suzuki H, Sasaki H, Nagahara A, Asaoka D, Matsuhisa T, Masaoaka T, Nishizawa T, Suzuki M, Ito M, Kurihara N, Omata F, Mizuno S, Torii A,
268
Kawakami K, Ohkusa T, Tokunaga K, Mine T, Sakaki N. Changes in the first line
269
Helicobacter pylori eradication rates using the triple therapy-a multicenter study in
270
the Tokyo metropolitan area (Tokyo Helicobacter pylori study group). J
271
Gastroenterol Hepatol 2014;29 Suppl 4:29-32.
M
16.
Sanchez JE, Saenz NG, Rincon MR, Martin IT, Sanchez EG, Martinez MJ.
ed
272
an
267
273
Susceptibility
274
quinupristin/dalfopristin
275
2000;46:283-5.
277
quinolones.
mupirocin, J
oxazolidinones,
Antimicrob
Chemother
Matsuzaki J, Suzuki H, Nishizawa T, Hirata K, Tsugawa H, Saito Y, Okada S, pylori after failures of first- and second-line therapies. Antimicrob Agents
279
Chemother 2012;56:1643-5.
18.
281
Hirata Y, Ohmae T, Yanai A, Sakitani K, Hayakawa Y, Yoshida S, Sugimoto T, Mitsuno Y, Akanuma M, Yamaji Y, Ogura K, Maeda S, Koike K. Sitafloxacin
282
resistance in Helicobacter pylori isolates and sitafloxacin-based triple therapy as a
283 284
new
to
Fukuhara S, Hibi T. Efficacy of sitafloxacin-based rescue therapy for Helicobacter
278 280
and
pylori
pt
17.
Helicobacter
Ac ce
276
of
third-line regimen in Japan. Int J Antimicrob Agents 2012;39:352-5.
19.
Murakami K, Furuta T, Ando T, Nakajima T, Inui Y, Oshima T, Tomita T, Mabe K,
285
Sasaki M, Suganuma T, Nomura H, Satoh K, Hori S, Inoue S, Tomokane T, Kudo M,
286
Inaba T, Take S, Ohkusa T, Yamamoto S, Mizuno S, Kamoshida T, Amagai K,
287
Iwamoto J, Miwa J, Kodama M, Okimoto T, Kato M, Asaka M. Multi-center
288
randomized controlled study to establish the standard third-line regimen for
289
Helicobacter pylori eradication in Japan. J Gastroenterol 2013;48:1128-35.
17 Page 17 of 18
290
20.
Sugimoto M, Sahara S, Ichikawa H, Kagami T, Uotani T, Furuta T. High
291
Helicobacter pylori cure rate with sitafloxacin-based triple therapy. Aliment
292
Pharmacol Ther 2015;42:477-83. 21.
294 295
Lam SK, Talley NJ. Report of the 1997 Asia Pacific Consensus Conference on the management of Helicobacter pylori infection. J Gastroenterol Hepatol 1998;13:1-12.
22.
Miner P, Jr., Katz PO, Chen Y, Sostek M. Gastric acid control with esomeprazole,
ip t
293
296
lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study.
297
Am J Gastroenterol 2003;98:2616-20. 23.
Rohss K, Wilder-Smith C, Naucler E, Jansson L. Esomeprazole 20mg provides more
cr
298
effective intragastric Acid control than maintenance-dose rabeprazole, lansoprazole
300
or pantoprazole in healthy volunteers. Clin Drug Investig 2004;24:1-7.
301
24.
us
299
Tankovic J, Lascols C, Sculo Q, Petit JC, Soussy CJ. Single and double mutations in gyrA but not in gyrB are associated with low- and high-level fluoroquinolone
303
resistance in Helicobacter pylori. Antimicrob Agents Chemother 2003;47:3942-4.
304
25.
an
302
Furuta T, Sugimoto M, Kodaira C, Nishino M, Yamade M, Uotani T, Sahara S, Ichikawa H, Yamada T, Osawa S, Sugimoto K, Watanabe H, Umemura K.
306
Sitafloxacin-based third-line rescue regimens for Helicobacter pylori infection in
307
Japan. J Gastroenterol Hepatol 2014;29:487-93. 26.
McNicholl AG, Linares PM, Nyssen OP, Calvet X, Gisbert JP. Meta-analysis:
ed
308
M
305
309
esomeprazole or rabeprazole vs. first-generation pump inhibitors in the treatment of
310
Helicobacter pylori infection. Aliment Pharmacol Ther 2012;36:414-25. 27.
Sakurai Y, Mori Y, Okamoto H, Nishimura A, Komura E, Araki T, Shiramoto M.
pt
311
Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or
313
rabeprazole 10 mg in healthy adult male subjects--a randomised open-label
314 315
cross-over study. Aliment Pharmacol Ther 2015;42:719-30.
28.
316
Mori H, Suzuki H, Matsuzaki J, Tsugawa H, Fukuhara S, Miyoshi S, Hirata K, Seino
317
T,
Matsushita
M,
Masaoka
T,
Kanai
T.
Efficacy
of
10-day
Sitafloxacin-Containing Third-Line Rescue Therapies for Helicobacter pylori Strains
318 319
Ac ce
312
Containing the gyrA Mutation. Helicobacter 2015.
29.
Fallone CA, Chiba N, van Zanten SV, Fischbach L, Gisbert JP, Hunt RH, Jones NL,
320
Render C, Leontiadis GI, Moayyedi P, Marshall JK. The Toronto Consensus for the
321
Treatment
322
2016;151:51-69 e14.
of
Helicobacter
pylori
Infection
in
Adults.
Gastroenterology
323 324
18 Page 18 of 18
