Case Control Study Open Access
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2021; 27(31): 5247-5258
Published online Aug 21, 2021. doi: 10.3748/wjg.v27.i31.5247
Tailored eradication strategy vs concomitant therapy for Helicobacter pylori eradication treatment in Korean patients
Youn I Choi, Jun-Won Chung, Kyoung Oh Kim, Kwang An Kwon, Yoon Jae Kim, Jung Ho Kim, Ja Young Seo, Dong Kyun Park
Youn I Choi, Jun-Won Chung, Kyoung Oh Kim, Kwang An Kwon, Yoon Jae Kim, Jung Ho Kim, Dong Kyun Park, Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
Ja Young Seo, Department of Laboratory Medicine, Gil Medical Center, Gachon University, Inchoen 21565, South Korea
Dong Kyun Park, Health IT Research Center, Gachon University Gil Hospital, Incheon 21565, South Korea
ORCID number: Youn I Choi (0000-0001-6561-6752); Jun-Won Chung (0000-0002-0869-7661); Kyoung Oh Kim (0000-0002-5365-2550); Kwang An Kwon (0000-0002-2947-2111); Yoon Jae Kim (0000-0001-8477-6823); Jung Ho Kim (0000-0002-6944-473X); Ja Young Seo (0000-0002-1894-1365); Dong Kyun Park (0000-0002-2862-6641).
Author contributions: Chung JW contributed to the study concept and design, coordinated all of the study processes as the corresponding authors; Choi YI and Seo JY analyzed the data; Choi YI interpreted the data; Choi YI and Chung JW drafted the manuscript; Park DK, Kim KO, Kwon KA, Kim JH, and Kim YJ critically revised the manuscript for important intellectual content; all the authors approved the submitted draft.
Supported by National Research Foundation of Korea (NRF) funded by the Ministry of Education, No. NRF-2020R1F1A1076839.
Institutional review board statement: The Institutional Review Board of the Gil Medical Center (GMC) reviewed the study protocol and ethics. This study was conducted in accordance with the Declaration of Helsinki, and the study protocol was approved by the ethics committee of the GMC.
Informed consent statement: Patients were not required to give the informed consent to the study because the analysis used the anonymous data that were collected after each patient agreed to treatment.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Data sharing statement: The data used to support the findings of this study are available from the corresponding author upon request at (junwonchung@gilhospital.com)
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jun-Won Chung, MD, PhD, Professor, Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, South Korea. junwonchung@hanmail.net
Received: April 29, 2021
Peer-review started: April 29, 2021
First decision: June 3, 2021
Revised: July 9, 2021
Accepted: July 29, 2021
Article in press: July 29, 2021
Published online: August 21, 2021

Abstract
BACKGROUND

Antibiotic resistance to Helicobacter pylori (H. pylori) infection, which ultimately results in eradication failure, has been an emerging issue in the clinical field. Recently, to overcome this problem, an antibiotic sensitivity-based tailored therapy (TT) for H. pylori infection has received attention.

AIM

To investigate the efficacy and safety profiles of TT for H. pylori infection treatment compared to a non-bismuth quadruple therapy, concomitant therapy (CT) regimen.

METHODS

We included patients (> 18 years) with an H. pylori infection and without a history of Helicobacter eradication who visited the Gil Medical Center between March 2016 and October 2020. After being randomly assigned to either the TT or CT treatment group in 1 to 1 manner, patient compliance, eradication success rate (ESR), and patient-reported side effects profiles were assessed and compared between the two groups. H. pylori infection was diagnosed using a rapid urease test, Giemsa stain, or dual priming oligonucleotide polymerase chain reaction (DPO-PCR). Tailored eradication strategy based through the presence of a 23S ribosomal RNA point mutation. For the TT group, a DPO-PCR test, which detected A2142G and/or A2143G point mutations, and a clarithromycin resistance test were performed. Patients in the clarithromycin-resistant group were treated with a bismuth-containing quadruple combination therapy, while those with sensitive results were treated with the standard triple regimen.

RESULTS

Of the 217 patients with a treatment naive H. pylori infection, 110 patients [mean age: 58.66 ± 13.03, men, n = 55 (50%)] were treated with TT, and 107 patients [mean age: 56.67 ± 10.88, men, n = 52 (48.60%)] were treated with CT. The compliance (TT vs CT, 100% vs 98.13%, P = 0.30), and follow-up loss rates (8.18% vs 9.35%, P = 0.95) were not significantly different between the groups. The ESR after treatment was also not statistically different between the groups (TT vs CT, 82.73% vs 82.24%, P = 0.95). However, the treatment-related and patient-reported side effects were significantly lower in the TT group than in the CT group (22.77% vs 50.52%, P < 0.001).

CONCLUSION

The DPO-based TT regimen shows promising results in efficacy and safety profiles as a first-line Helicobacter eradication regimen in Korea, especially when physicians are confronted with increased antibiotic resistance rates.

Key Words: Helicobacter pylori, Eradication, Tailored therapy, Concomitant therapy regimen

Core Tip: We investigated the efficacy and safety profiles of a tailored therapy (TT) as a first line Helicobacter pylori (H. pylori) eradication treatment compared to a concomitant therapy (CT) regimen in Korea, where clarithromycin resistance rates are high. Of 217 treatment-naïve H. pylori infection patients, 107 patients were treated with CT and 101 patients with TT. Although the eradication success rate was not statistically different between the groups, the treatment-related side effect rate was significantly lower in the TT group. Therefore, the TT regimen might be a promising solution to overcoming the problem of increased antibiotic resistance rates for Helicobacter eradication.



INTRODUCTION

Helicobacter pylori (H. pylori) eradication is associated with a reduced risk of stomach cancer, including adenocarcinoma and mucosa-associated lymphoid tissue lymphoma, thus the rising global rates of antibiotic resistant H. pylori infections is concerning[1-4]. Currently, the Maastricht V/Florence Consensus guidelines, and Korean H. pylori treatment guidelines recommend proton pump inhibitor-based standard triple therapy[5-7]. However, the treatment success rate of standard tailored therapy (TT) has been declining worldwide over the past few decades as H. pylori drug resistance has increased year-over-year[4,7-9]. In Korea, a recent studying assessing the use of the standard triple therapy regimen for H. pylori eradication showed a treatment success rate of less than 70%[8-11]. Given that the ideal eradication success rate (ESR) should be over 80% in intention-to-treatment (ITT) analyses, and 90% in per-protocol (PP) analyses according to the 1997 Asia-Pacific Agreement Report for H. pylori treatment, conventional standard triple therapy with an empirically chosen policy has lost its role in H. pylori eradication practice[12].

Recently, to overcome the aforementioned problems of empirically chosen eradication policies, the concept of ‘TT’ has been introduced in the eradication policy for H. pylori infection[12-18]. TT for H. pylori eradication is based on a pre-treatment antibiotic resistance test using stool or stomach biopsy samples[18,19]. However, tissue culture based antibiotic resistance testing for H. pylori is not ideal in that it is costly, time consuming, and not all of the antibiotics used in the regimen can be tested. Instead, dual priming oligonucleotide polymerase chain reaction (DPO-PCR) has been used[20-22]. DPO-PCR tests are cost effective and less time consuming than tissue culture based tests[23,24]. However, DPO-PCR test is currently only available for clarithromycin (CLR) resistance testing, as a method for rapid metronidazole (MTZ) resistance testing for H. pylori has been invented clinically. However, Korea is a region with high CLR resistance. In fact, the resistance rate has gradually increased, from 22.9% in 2003–2005 to 37.0% in 2007–2009, with the major barriers for H. pylori eradication success being CLR resistance, prompting clinical data to be accumulated using DPO-PCR tests in H. pylori eradication regimens[9,25].

Unfortunately, there is little data on the efficacy and safety profiles of the TT regimen compared to the concomitant therapy (CT) regimen in first-line H. pylori eradication.

Herein, we investigated the efficacy (ESR) and safety profiles (treatment-related side effect events) of the TT regimen as compared to those of CT in patients with treatment-naïve H. pylori infections in Korea, where the CLR resistance rate is high (> 15%).

MATERIALS AND METHODS
Institutional review board approval

The Institutional Review Board of the Gil Medical Center (GMC) reviewed the study protocol and ethics. This study was conducted in accordance with the Declaration of Helsinki, and the study protocol was approved by the ethics committee of the GMC.

Enrolled study population

We enrolled patients (> 18 years) with evidence of an H. pylori infection who were treatment naïve for H. pylori eradication that visited the GMC (Incheon, Korea) between March 2016 and October 2020. Exclusion criteria for this study were as follows: (1) Patients under 18 years of age; (2) Patients with a history of previous eradication; (3) Patients with a history of an allergy to any medication used in this study; (4) Patients with any operation history regarding the stomach; (5) Seriously ill patients with critical medical history [heart failure (≥ New York Heart Association class II), severe respiratory illness, decompensated liver cirrhosis, terminal or supportive care stage of malignancy, etc.]; (6) Patients who could not afford to revisit the hospital for follow-up after medication; and (7) Patients who could not take medication orally.

Enrolled patients were randomly assigned to either the TT group or the CT group in a 1 to 1 manner and their compliance rates, ESRs, and treatment-related side effect rates were assessed (Figure 1).

Figure 1
Figure 1 Flow chart. TT: Tailored therapy; CT: Concomitant regimen; S: Sensitive; R: Resistance; PAC: Pancreatic adenocarcinoma; PBMT: Bismuth-containing quadruple combination; ITT: Intention-to-treat; PP: Per-protocol; H. pylori: Helicobacter pylori.
Diagnosis of H. pylori infection

All patients underwent an upper gastrointestinal endoscopy and showed positive results through a rapid urease test, Giemsa stain, or DPO-PCR.

PCR guided CLR resistance test for TT group

We used DPO-PCR to detect the presence of either a 2142G or 2143G point mutation on 23S rRNA. The point mutation in the V domain of 23S rRNA has been depicted as a major risk factor for CLR resistance against H. pylori, and 2142G and 2143G are the most frequent sites for 23S rRNA point mutations. The wild type for both 2142G and 2143 G mutations was defined as CLR sensitive.

Eradication regimen for TT group, and CT group

For the TT group, after the DPO-PCR test, patients who were deemed CLR resistant were administered a bismuth-containing quadruple combination (PBMT), and those who were CLR sensitive with a standard pancreatic adenocarcinoma (PAC) regimen (Figure 1). The bismuth-containing quadruple regimen consisted of 30 mg of lansoprazole twice daily + 500 mg MTZ twice daily + 300 mg bismuthate four times daily + 500 mg tetracycline four times daily for 10 d. The PAC regimen consisted of 30 mg lansoprazole + 500 mg CLR + 1000 mg amoxicillin (AMX), administered twice daily for 14 d.

The CT regimen consisted of 30 mg lansoprazole twice a day + 1 g AMX twice a day + 500 mg MTZ twice a day + 500 mg CLR twice a day for 10 d.

Follow up strategy, and outcome interpretation (efficacy and safety profiles)

Four weeks after finishing their eradication medication, patients were recommended to visit the GMC and undergo the 13C-ure breath test (UBT; UBiTkit; Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan) with a cut-off value of delta 13CO2 < 2.5‰ to evaluate eradication success. During this visit, the patients reported treatment-related side effects and drug compliance rates were also recorded by the physician.

Definition for treatment-related adverse events

Physicians interviewed enrolled patients regarding treatment-related adverse events at follow up. Patients were asked for their treatment-related adverse effects type as both of open-ended, and closed-ended questions. Items for closed-ended questions regarding treatment-related side effect types were as follows: (1) Taste disturbance; (2) Nausea/vomiting; (3) Diarrhea/Loose stool/constipation; (4) Abdominal discomfort, dyspepsia; (5) General weakness, myalgia; (6) Dizziness, head ache; and (7) Skin rash.

The degree of treatment-related side effect were classified as ‘mild’, ‘moderate’, and ‘severe’ events according to the degree of tolerance of patients’ daily activities as follows: No adverse events; mild (without limitation in daily activities); moderate (partly limited daily activities); and severe (completely limited daily activities). Patients were instructed to visit hospital immediately when any severe adverse events occurred.

Definition for treatment compliance

Treatment compliance was defined according to the status of the consumption of the prescribed drugs through personal interviews at the follow-up visit. The compliance level was investigated through patients’ self-reported questionnaire, and consumed/ remained medication pill counts. Patients who consumed > 80% of the scheduled prescription were classified as having good compliance.

Statistics

Treatment outcomes (efficacy profiles and safety profiles) were analyzed using an ITT analysis and PP analysis. In the ITT analysis, after excluding patients meeting the exclusion criteria, all of the enrolled study population were included. In PP analyses, patients who were lost to follow-up or those with poor compliance (< 80%) were excluded. Categorical variables were analyzed as percentiles and compared between the TT and CT groups using the chi-square test. Continuous variables were represented as mean ± SD and were compared between groups using Student’s t-test. Statistical significance was set to P < 0.05. The Statistical Package for the Social Sciences (SPSS) software (version 22.0; IBM Corp., Armonk, NY, United States) was used for statistical analyses.

RESULTS
Clinical characteristics

Of the 217 patients with a treatment-naive H. pylori infection, 110 [men: n = 55 (50.00%); mean age: 58.66 ± 13.03] were treated with TT, and 107 with CT [men: n = 52 (48.60%); mean age: 56.67 ± 10.88] (Table 1). The rates of endoscopy, smoking, drinking, and comorbidity status were not significantly different between the groups (Table 1).

Table 1 Baseline characteristics of the study population.

TT group (n = 110)
CT group (n = 107)
P value
Age, mean ± SD (yr)58.66 ± 13.0356.67 ± 10.880.22
Men, n (%)55 (50.00)52 (48.60)0.89
Body mass index (m2/kg)24.31 ± 3.2323.87 ± 2.910.35
Smoking, n (%)24 (22.82)22 (20.59)0.74
Drinking, n (%)30 (30.00)28 (26.17)0.39
Comorbidity0.81
Hypertension, n (%)26 (23.64)23 (21.50)
Diabetes mellitus, n (%)22 (20.00)25 (23.36)
Cardiovascular disease, n (%)2 (1.82)2 (1.86)
Reasons for eradication0.37
Peptic ulcer disease49 (44.54)43 (40.19)
Post ESD due to EGC4 (3.63)2 (1.87)
MALToma0 (0.00)1 (0.93)
Chronic atrophic gastritis with intestinal metaplasia57 (51.82)61 (57.01)
Clarithromycin resistance diagnosed by DPO-PCR
No, n (%)81 (73.64)
A2142G positive, n (%)4 (3.64)
A2143G positive, n (%)25 (22.73)
Follow up loss, n (%)9 (8.18)10 (9.35)0.95
Poor compliance, n (%)0 (0.00)2 (0.02)0.30

After evaluating CLR resistance status using DPO-PCR test, of the 101 patients who were initially allocated to the TT group, 29 (26.36%) tested positive for CLR-resistant H. pylori, while 81 (73.64%) were classified as CLR-sensitive (Table 1). Among the 29 patients with CLR-resistant H. pylori, four patients showed a A2142G point mutation, while the other 25 patients showed a A2143G point mutation (Table 1).

Follow up loss rate and compliance status of TT vs CT group

The follow-up loss (TT vs CT; 8.18% vs 9.35%, P = 0.95) and poor compliance rates (0% vs 1.87%, P = 0.33) were not significantly different between the groups (Table 1).

Efficacy profiles (ESR) of TT vs CT group

In the ITT protocol, ESR after treatment was not significantly different between the groups (82.73% vs 82.24%, P = 0.95) (Table 2).

Table 2 Helicobacter pylori eradication success rates.
Eradication rate
TT group (n = 110)
CT group (n = 107)
P value
Intention-to-treat91/110 (82.73)88/107 (82.24)0.95
Per-protocol91/101 (90.10)87/951 (91.58)0.72

Additionally, in the PP protocol, the TT group showed a lower ESR than the CT group (90.10% vs 91.58%, P = 0.72), but the difference was not statistically significant (Table 2).

ESR in TT group according to DPO-PCR results

When we determined ESR in the TT group according to the DPO-PCR results, a total of 72 patients showed CLR sensitive results (treated with PAC regimen), with the ESR for those patients being 80.25%, and 87.84% in the ITT and PP analyses, respectively (Table 3). Four patients showed an A2142G point mutation with ESR of (3/4) 75.00% and (3/3) 100% in the ITT and PP analyses, respectively (Table 3). Twenty-five patients with an A2143G point mutation showed an ESR of 92.00% and 95.83% in ITT and PP analyses, respectively (Table 3).

Table 3 Eradication success rate in tailored therapy group according to dual priming oligonucleotide polymerase chain reaction results.
Eradication rate
No mutation
A2142G positive
A2143G positive
Number of patients who initially enrolled81425
Number of patients with eradication failure901
Number of patients lost to follow up711
Number of patients with poor compliance000
Eradication success rate
Intention-to-treat65/81 (80.25%)3/4 (75.00%)23/25 (92.00%)
Per-protocol65/74 (87.84%)3/3 (100%)23/24 (95.83%)
Patient reported treatment-related side effect profiles of TT vs CT group

Treatment-related and patient-reported side effect events were significantly lower in the TT group than in the CT group (22.77% vs 50.52%, P < 0.001) (Table 4).

Table 4 Treatment related adverse events, n (%).

TT group (n = 1011)
CT group (n = 972)
P value
Eradication related Side effects< 0.001
No 78 (77.23)48 (49.48)
Yes23 (22.77)49 (50.52)
Taste disturbance 2 (1.98)18 (18.56)
Nausea/vomiting10 (9.90)15 (15.46)
Diarrhea/loose stool/constipation6 (5.94)9 (9.28)
Abdominal discomfort, dyspepsia3 (2.97)3 (3.09)
General weakness, myalgia 1 (0.99)1 (1.03)
Dizziness, headache1 (0.99)2 (2.06)
Skin rash0 (0.00)1 (1.03)

The most common side effect was nausea/vomiting [n = 9 (10.23%)] in the TT group and taste disturbance [n = 18 (18.56%)] in the CT group (Table 4).

DISCUSSION

In this study, we investigated the efficacy (ESR) and safety profiles of TT as a first-line H. pylori eradication regimen compared to those of CT in Korea, where the CLR resistance rate is increasing (> 15%). According to our study results, the ESR between the TT and CT groups was not statistically different between the groups. However, the TT group showed a significantly lower treatment-related side effect rate as compared to that of the CT regimen. Considering that lower exposure to antibiotics and appropriate drug use are the best policies for reducing the spread of antibiotic-resistant bacteria[26,27], the TT regimen might be a promising H. pylori eradication strategy in an era where increased risk for antibiotic resistance has become a huge medical burden, as is the case in Korea.

Even though the CT regimen for H. pylori eradication has shown high ESR in Korea until recently, when compared to that of conventional TT, and even sequential treatment, several concerns arise with this regimen[14,28-34]. First, since the CT regimen includes multiple antibiotic medications for H. pylori eradication such as CLR, AMX, and MTZ, there is a possibility of antibiotic overuse[30,31,35]. Given that indiscriminate misuse of antibiotics is related to the emergence of multidrug resistance bacteria, not just limited to H. pylori, appropriate use of antibiotics based on drug sensitivity analysis has been emphasized in solving the current multidrug resistance problems of bacteria[27,35]. Even if the CT regimen is effective in H. pylori eradication, there is room for antibiotic overuse, which might result in violating antibiotic stewardship, thus physicians should only use a CT regimen with extreme caution[13,27,30,36,37]. Second, because the CT regimen contains multiple antibiotic options, higher incidences of treatment-related side effects, which are related to poor treatment compliance, and ultimately result in eradication failure, have been reported in previous studies[31,32,38,39]. According to our findings, the CT group showed a statistically higher incidence of treatment-related side effects than the TT group.

The paradigm shift from empirically chosen eradication policy to bacteria-specific targeted therapy in H. pylori eradication, TT, originated from the rise of precision medicine and ab accumulation of data on resistance mechanisms of H. pylori infection[11,15,16,25,37,40-42]. According to a meta-analysis by Venerito et al[43] that analyzed the effect of antibiotic sensitivity of H. pylori on ESR, a conventional triple regimen yielded an ESR of 80%–95% among CLR-sensitive strains, but dropped to 0%–48% among CLR resistant strains[43,44]. Therefore, CLR resistance significantly affected the ESR of the conventional triple regimen[43]. However, MTZ resistance was not significantly associated with the ESR of PBMT even in MTZ-resistant strains as compared to that in MTZ-sensitive strains[43]. Therefore, confirming CLR susceptibility before eradication in order to use a tailored eradication was closely associated with an improved ESR as compared to that of the empirically chosen conventional triple regimen, regardless of the MTZ resistance test results[ 19-21,41,45-47].

To date, several antibiotic resistance mechanisms of H. pylori infection have been proposed[48]. First, antimicrobial genes that are expressed as key targeted structures, such as cell membranes, nucleic acids, DNA gyrases, DNA-dependent RNA polymerases, and redox enzymes, mutate to evade antibiotics, such as quinolone series resistant H. pylori. Second, the efflux systems of H. pylori change to prohibit the intracellular accumulation of antibiotics. Third, H. pylori enzymes that inactivate antibiotic compounds are activated or produced. Among these mechanisms, the CLR resistance phenomenon for H. pylori infection mainly originates from the mutation of the cellular target genes, especially associated with protein translation in the V domain of 23S rRNA (A2143G, A2142C, A2142G, A2143C, etc.)[48-50]. In our study, we used the DPO-PCR test for CLR resistance detection, which specifically targeted the A2143G and A2142G point mutations. Among the 101 patients in the TT group, 72 of them showed CLR sensitivity, while 29 showed CLR resistance. Even among patients with a negative DPO-PCR test result (n = 72), who were classified with wild-type H. pylori strains against CLR, and prescribed the conventional triple regimen, the ESRs were 70.83% and 78.46% in the ITT and PP analyses, respectively. This phenomenon might have resulted from mutations in the V domain of 23S rRNA other than A2142G and A2143G point mutations, which were not detected in the DPO-PCR test we used. Considering cost effectiveness, we targeted H. pylori strains with the most common site of point mutations resulting in CLR resistance. It is possible that the H. pylori strains classified as wild type through the DPO-PCR test were not really wild type. However, among the patients who showed a 2142G or A 2143 G point mutation via the DPO-PCR test, the ESR of the PBMT regimen was 100% and 90.48%, respectively, in the PP analysis. Efforts to develop cost-effective and multiple point mutation detection kits for H. pylori should be continued in order to improve the ESR of TT[23,24,51].

Even though there is limited data on the efficacy of the TT regimen in H. pylori treatment policy, there have been several studies assessing TT efficacy profiles compared to that of the CT regimen[45,52,53]. For example, Ong et al[52] conducted a randomized controlled study comparing the treatment outcomes of TT regimen vs CT regimen, and reported that in ITT analyses, the TT regimen group showed a higher eradication rate compared the CT regimen group[52]. As for treatment-related side effect events, the TT group also showed fewer events during treatment than the CT group. While this study was conducted in Pusan, Korea, which is far from Incheon, Korea, where the GMC is located, similar treatment outcomes were induced even though the CLR resistance rates differed between the cities.

Furthermore, Lesprit et al[27] reported that a tailored H. pylori eradication strategy based on the presence of a 23S ribosomal RNA point mutation that causes CAM resistance in patients with H. pylori infection is more cost effective than empirical treatment[27]. Kim et al[25] also conducted an economic modeling study comparing TR based on DPO-PCR and empirical treatment.

Even efficacy of TT regimen in treating H. pylori infection has been evaluated, cost-effectiveness of TT regimen should be evaluated to be widely used in clinical practice in Korea. Tailored regimen needs additional diagnostic procedure of antibiotic resistance test such as DPO-PCR. Even it varies depending on insurance coverages, DPO-PCR costs approximately $55.24 more than rapid urease test in Korea[23]. In this regards, several previous studies investigated medical costs of H. pylori tailored eradication strategy as compared to empirical first line eradication strategy (CLR based triple regimen) in Korea[23]. Cho et al[23] reported that it is acceptable level of predictive additional costs (only an extra $3.96 per eradicated patient) for tailored H. pylori eradication strategy with DPO-CPR as compared to CLR based conventional triple therapy[23]. In our study, we compared efficacy and safety level of TT vs CT regimen, and should discuss the medical cost effectiveness of TT vs CT regimen. However, there has been little data to investigate medical cost of TT strategy as compared to CT regimen. One would say medical cost of TT regimen might be much higher than that of CT regimen, since ESR of empirical CT regimen is generally much higher than empirical CLR based triple regimen. Not just considering each patient’s medical cost during Helicobacter eradication, but also given that worrisome issues on increased prevalence of drug resistance bacteria in worldwide, tailored approaches in treating H. pylori infection should be considered following the major principle of antibiotic use guidelines, antibiotic sensitivity result-based treatment.

Limits of the study

There are several limitations to this study. First, although we prospectively and randomly assigned patients to either the TT or CT group, we retrospectively reviewed the data. Second, since this study was conducted in a tertiary center located in Incheon, Korea, we applied our research results to other regions with caution. In a previous study, researchers investigated the CLR resistance rate for H. pylori infection in Incheon, and reported a CLR resistance rate of approximately 30%[54]. Although the aforementioned study was not conducted in our hospital, the GMC, the CLR resistance for H. pylori infection is similar to our study. Given that different regions might differ in H. pylori infection status and antibiotic resistance status, more multicenter and multinational studies are needed. Third, since we did not culture H. pylori for the antibiotic sensitivity test, but instead replaced it with a DPO-PCR test, and are therefore subject to the pit falls of a DPO-PCR. Nevertheless, in a previous study, the DPO-PCR test was validated alongside a culture-based antibiotic resistance test and showed approximately 98% accuracy[20,55].

CONCLUSION

Despite the aforementioned limitations, this study focused on the efficacy and safety profiles of the TT regimen compared to those of the CT regimen in a relatively large dataset in Korea. For the rapidly rising antibiotic resistance rate, the most active countermeasure is to perform an antibiotic resistance test for the strain and actively select the appropriate antibiotic and then decide on the treatment.

In conclusion, according to our study results, the TT regimen showed promising results in terms of efficacy and safety profiles for the first-line regimen of H. pylori eradication as compared to those of the CT regimen. Therefore the DPO-based TT regimen might be a successful option for H. pylori eradication, especially when physicians are confronted with increased antibiotic resistance rates for H. pylori eradication.

ARTICLE HIGHLIGHTS
Research background

Antibiotic resistance to Helicobacter pylori (H. pylori) infection has been an emerging issue in the clinical field. Recently, to overcome this problem, an antibiotic sensitivity-based tailored therapy (TT) for H. pylori infection has got attention.

Research motivation

However, there is limited data regarding efficacy of TT strategy in treatment of H. pylori infection in Korea as compared to that of concomitant therapy (CT) regimen.

Research objectives

To investigate the efficacy and safety profiles of TT for H. pylori infection treatment compared to a non-bismuth quadruple therapy, CT.

Research methods

We included treatment naive H. pylori infection patients (> 18 years) who visited the Gil Medical Center between March 2016 and October 2020. After randomly assigned to either the TT or CT treatment group in 1 to 1 manner, patient compliance, eradication success rate (ESR), and patient-reported side effects profiles were compared between the two groups. For the TT group, a dual priming oligonucleotide polymerase chain reaction (DPO-PCR) test, which detected A2142G and/or A2143G point mutations, and a clarithromycin (CLR) resistance test were performed. Patients in the CLR-resistant group were treated with a bismuth-containing quadruple combination therapy, while those with sensitive results were treated with the standard triple regimen.

Research results

Of the 217 patients with a treatment naive H. pylori infection, 110 patients [mean age: 58.66 ± 13.03, men, n = 55 (50%)] were treated with TT, and 107 patients [mean age: 56.67 ± 10.88, men, n = 52 (48.60%)] were treated with CT. The compliance (TT vs CT, 100% vs 98.13%, P = 0.30), and follow-up loss rates (8.18% vs 9.35%, P = 0.95) were not significantly different between the groups. The ESR after treatment was also not statistically different between the groups (TT vs CT, 82.73% vs 82.24%, P = 0.95). However, the treatment-related and patient-reported side effects were significantly lower in the TT group than in the CT group (22.77% vs 50.52%, P < 0.001).

Research conclusions

The DPO-based TT regimen shows promising results in efficacy and safety profiles as a first-line Helicobacter eradication regimen in Korea, especially when physicians are confronted with increased antibiotic resistance rates.

Research perspectives

The DPO-based TT regimen might role as a first-line Helicobacter eradication regimen with similar efficacy and safety profiles as compared to CT regimen.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: South Korea

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

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Grade E (Poor): 0

P-Reviewer: Couto ME, Smith SM S-Editor: Fan JR L-Editor: A P-Editor: Xing YX

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