The eradication rate of Helicobacter pylori using the empirical standard triple therapy (STT) has declined to less than 80% over the past two decades in Korea.^1,2 This reduced eradication rate is largely attributable to the clarithromycin-resistant H. pylori.³ According to revised Korean guidelines for the treatment of H. pylori infection in Korea,⁴ empirical STT for 14 days is recommended as the first-line eradication therapy since the H. pylori eradication rate after a 14-day regimen is higher than that of a 7-day regimen. By contrast, the new guidelines recommend a 7-day regimen, rather than a 14-day regimen, for tailored STT based on prior clarithromycin resistance testing. For patients who either are intolerant to other eradication therapies or have clarithromycin-resistant H. pylori, bismuth-quadruple therapy (BQT) for 10 to 14 days is considered the first-line eradication therapy.

To date, the effective duration for tailored STT and BQT first-line eradication therapies is not clear. The aim of this study was to investigate the effective duration of tailored STT and tailored BQT as a first-line eradication therapy based on the prior identification of the clindamycin-susceptibility of H. pylori, using dual priming oligonucleotide-based multiplex polymerase chain reaction (DPO-PCR).

1. Study design and subjects

The electronic medical cohort database of consecutive H. pylori-positive patients who underwent upper gastrointestinal endoscopy and DPO-PCR for H. pylori in a single tertiary center (Incheon St. Mary’s Hospital, the Catholic University of Korea) from September 2019 to December 2020 was retrospectively reviewed. Inclusion criteria for this study were as follows: (1) H. pylori-positive in Giemsa stain; (2) DPO-PCR before eradication therapy; (3) adult patients aged 20 to 75 years; and (4) disease entities such as chronic atrophic gastritis with or without intestinal metaplasia, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and endoscopic resection of early gastric cancer. Exclusion criteria for patients were as follows: (1) a history of gastrectomy; (2) concomitant systemic diseases such as severe liver function abnormalities, renal insufficiency, cardiovascular diseases, cerebrovascular diseases, and pulmonary diseases that were not suitable for H. pylori eradication; (3) a history of allergic reaction to antibiotics; (4) judged unsuitable by endoscopists; and (5) did not consent to the DPO-PCR test.

Based on DPO-PCR results from H. pylori-positive patients, patients were classified to either a clarithromycin susceptible group (absence of H. pylori 23S ribosomal RNA point mutations; wild type) or a clarithromycin-resistant group (presence of H. pylori 23S ribosomal A2142G and/or A2143G 23S point mutations). This study was approved by the Institutional Review Board of the Incheon St. Mary’s Hospital, the Catholic University of Korea, Incheon (IRB number: OC22RASI0021). Since this study was based on retrospectively collected data, patient informed consent was exempted, and this study complied with the ethical principles of the Declaration of Helsinki.

2. DPO-PCR for clarithromycin resistance

Standard tissue biopsies for the determination of clarithromycin susceptibility were taken from at least one point each in the body and antrum of the stomach, excluding the lesion sites. The clarithromycin resistance of H. pylori was determined by DPO-PCR using the Seeplex^Ⓡ ClaR-H. pylori ACE Detection kit (Seegene Inc., Seoul, Korea) according to the manufacturer's recommendations.⁵ DPO which has two priming sites (5'-end stabilizer and 3'-end determiner) by a polydeoxyinosine linker, specifically amplifies only the target gene through dual priming process, enables unparalleled specificity by eliminating any false extension. The Seeplex^Ⓡ ClaR-H. pylori ACE Detection kit includes three primer pairs with a DPO structure that allows amplification of the wild-type H. pylori 23S ribosomal RNA (621 base pair amplicon) and the A2142G (194 base pair amplicon) and A2143G (475 base pair amplicon) mutations.⁶ The results were considered susceptible to clarithromycin when the wild-type 23S ribosomal RNA allele was amplified or resistant to clarithromycin if either of the two mutant alleles was present.

3. Study regimens

The STT regimen for treatment of the clarithromycin susceptible group was lansoprazole 30 mg twice a day, amoxicillin 1,000 mg twice a day, and clarithromycin 500 mg two twice a day, for either 7 days or 14 days. For treatment of the clarithromycin-resistant group, the BQT regimen comprised lansoprazole 30 mg twice a day, tripotassium dicitrate bismuthate 300 mg four times a day, metronidazole 500 mg three times a day, and tetracycline 500 mg four times a day, for either 7 days or 14 days. When selecting the 7-day or 14-day regimens for STT and BQT, the patients were chosen arbitrarily.

4. Confirmation of eradication success

After the tailored eradication treatment, a ¹³C-urea breath test (¹³C-UBT) was performed 6 to 8 weeks after the end of treatment administration, on all subjects, to determine whether the eradication had been successful. Patients discontinued taking proton pump inhibitor or H₂ blockers at least 2 weeks before the ¹³C-UBT. On the day of the test, patients fasted for at least 4 hours before taking 100 mg of ¹³C-urea (UBIT^Ⓡ; Otsuka Pharmaceutical, Tokyo, Japan) with 100 mL of water. After 20 minutes, ¹³C-UBT (POCone^Ⓡ; Otsuka Electronics, Osaka, Japan) was performed. Based on the measurements of ¹³CO₂ levels in the expired breath by mass spectrometry, a value exceeding 2.5‰ was defined as positive and indicated that the eradication had failed.

5. Outcome measures

The primary outcomes of this study were comparison of eradication rates for the 7- and 14-day STT treatments, as a first-line therapy in the clarithromycin susceptible group, and comparison of eradication rates for the 7 and 14 days of BQT, as a first-line therapy in the clarithromycin-resistant group. The eradication rates in each group were calculated by intention-to-treat (ITT) and per-protocol (PP) analyses. ITT was expressed as a percentage of all patients who took the medicine, including those with poor compliance, with drop out due to the severe adverse effects, or with lack of follow-up. The PP eradication rate was expressed as a percentage of those patients who completed the study. The secondary endpoints were comparisons of adverse effects and compliance by treatment regimens and durations. Patient-reported adverse effects and compliance were checked when the ¹³C-UBT was performed at the last hospital visit. Major adverse effects were defined as cases when the selected regimen could not be continuously taken due to adverse effects, and adverse effects that did not affect the study results were defined as minor adverse effects. Patients with poor compliance were defined as consumption of less than 90% of the prescribed medicines and were excluded from the PP analysis.

6. Statistical analysis

All statistical analyses were computed using SPSS software (version 28.0; IBM Corp., Armonk, NY, USA). Continuous variables were presented as means and standard deviations and were compared with the Student t-test. Categorical variables were presented as numbers and proportions and compared by using the chi-square test or Fisher exact test, as appropriate. A value of p<0.05 was considered statistically significant.

1. Baseline characteristics

ClaR-H. pylori DPO-PCR was carried out on biopsies from 184 patients who were H. pylori-positive and met the inclusion criteria. The overall clarithromycin resistance rate was 41.3% (76/184). For the presence of a 23S ribosomal RNA point mutation, A2142G mutant was present in four patients (5.3%) and A2143G mutant was present in 72 patients (94.7%), and there was no double mutant (A2142G and A2143G).

The baseline characteristics of enrolled participants in this study are shown in Table 1. In the STT study, there were no significant differences in the baseline characteristics of patients assigned to the 7-day or 14-day treatment groups. However, the number of patients who underwent endoscopic resection due to early gastric cancer was higher (30.8% vs 12.5%, p=0.02) in the 14-day treatment group. In the BQT group, the only difference between the 7-day and 14-day groups was their mean age. The mean age of patients in the 14-day treatment group was 59.7±8.8 years old compared with 67.0±9.8 years old (p=0.001) in the 7-day group. There was no significant difference in the prevalence of the A2143G point mutation type (92.9% vs 97.1%, p=0.624) between the 7-day and 14-day BQT groups, which can significantly affect the success of eradication treatments.

Table 1 . Baseline Characteristics of the Study Population.

Characteristics	STT 7 (n=56)	STT 14 (n=52)	p-value	BQT 7 (n=42)	BQT 14 (n=34)	p-value
Age, yr	61.2±12.4	62.2±9.0	0.66	67.0±9.8	59.7±8.8	0.001
Male sex	30 (54.6)	25 (48.1)	0.57	14 (33.3)	17 (50.0)	0.14
Body mass index, kg/m2	24.1±3.1	23.8±3.5	0.24	24.2±2.8	24.5±3.0	0.51
Smoking (current)	13 (23.2)	10 (19.2)	0.61	6 (14.3)	7 (20.6)	0.47
Alcohol (current)	34 (60.7)	30 (57.7)	0.75	23 (54.8)	20 (58.8)	0.72
Indications
H. pylori-associated chronic gastritis	37 (55.4)	25 (48.1)	0.06	26 (61.9)	21 (61.8)	0.99
Gastric ulcer	8 (14.3)	5 (9.6)	0.46	3 (7.1)	2 (5.9)	1.00
Duodenal ulcer	4 (7.1)	6 (11.5)	0.52	2 (4.8)	5 (14.7)	0.23
ER of EGC	7 (12.5)	16 (30.8)	0.02	11 (26.2)	6 (17.6)	0.37
MALToma	0	0	NA	0	0	NA
23S ribosomal RNA point mutation type			NA			0.624
A2142G	NA	NA		3 (7.1)	1 (2.9)
A2143G	NA	NA		39 (92.9)	33 (97.1)
Double (A2142G and A2143G)	NA	NA		0	0

Data are presented as mean±SD or number (%)..

STT, standard triple therapy; BQT, bismuth-quadruple therapy; H. pylori, Helicobacter pylori; ER, endoscopic resection; EGC, early gastric cancer; MALToma, mucosa-associated lymphoid tissue lymphoma; NA, not available..

2. H. pylori eradication rates

One hundred and eight patients with a wild-type ClaR DPO-PCR result received either 7-day or 14-day STT, and 76 patients with a mutant ClaR DPO-PCR result received 7-day or 14-day BQT. Of the 56 patients assigned to the 7-day STT, four patients were lost to follow-up, two patients discontinued the drug regimen due to adverse effects, and two patients were excluded due to poor compliance, leaving 48 patients who were subjected to PP analysis. Similarly, in the 14-day STT group, three patients were lost to follow-up, and two patients were excluded due to poor compliance, leaving 47 patients who were subjected to PP analysis. In the 7-day BQT group, four patients were lost to follow-up, one patient discontinued the drug regimen due to adverse effects, and two patients were excluded due to poor compliance. In the 14-day BQT group, one patient was lost to follow-up, one patient discontinued the drug regimen due to adverse effects, and one patient was excluded due to poor compliance. The schematic flow of this study is shown in Fig. 1.

Figure 1. Schematic flowchart of patients in this study.
DPO-PCR, dual priming oligonucleotide-based multiplex polymerase chain reaction; ITT, intention-to-treat; PP, per-protocol; STT, standard triple therapy; BQT, bismuth-quadruple therapy.

There was no significant difference in H. pylori eradication rate between the 7-day and 14-day STT groups. ITT data showed that H. pylori was eradicated in 76.8% (95% confidence interval [CI], 66.1% to 87.5%) of patients on the 7-day treatment and 78.8% (95% CI, 67.3% to 90.4%; p=0.80) of patients on the 14-day treatment. PP data revealed that H. pylori was eradicated in 89.6% (95% CI, 81.3% to 97.9%) of patients on the 7-day treatment and 87.2% (95% CI, 76.6% to 95.7%; p=0.72) of patients on the 14-day treatment. Similarly, for BQT, the H. pylori eradication rate was comparable between the 7-day and 14-day groups. For the ITT cohort, successful eradication was achieved in 76.2% (95% CI, 61.9% to 88.1%) of patients on the 7-day treatment and 82.4% (95% CI, 67.6% to 94.1%; p=0.51) of patients on the 14-day treatment; for the PP cohort, 91.4% (95% CI, 80.0% to 100%) and 90.3% (95% CI, 77.4% to 100%; p=0.60) eradication was achieved for the 7-day and 14-day treatments, respectively. Overall eradication rates were 88.4% (95% CI, 81.1% to 94.7%) in patients on STT and 90.9% (95% CI, 83.3% to 97.0%) in patients on BQT in the PP analysis (p=0.61). Drug compliance was higher than 90% in all four treatment groups, and there was no significant difference in compliance between the 7-day and 14-day groups for either regimen. The results are summarized in Table 2.

Table 2 . Helicobacter pylori Eradication Rates with STT and BQT Therapies for Each Duration.

Analysis	STT 7 (n=56)	STT 14 (n=52)	p-value	BQT 7 (n=42)	BQT 14 (n=34)	p-value
ITT analysis
Eradication rate	43/56 (76.8)	41/52 (78.8)	0.80	32/42 (76.2)	28/34 (82.4)	0.51
95% CI, %	66.1–87.5	67.3–90.4		61.9–88.1	67.6–94.1
PP analysis
Eradication rate	43/48 (89.6)	41/47 (87.2)	0.72	32/35 (91.4)	28/31 (90.3)	0.60
95% CI, %	81.3–97.9	76.6–95.7		80.0–100	77.4–100
Overall PP analysis
Eradication rate	84/95 (88.4)			60/66 (90.9)		0.61
95% CI, %	81.1–94.7			83.3–97.0
Compliance	48/52 (92.3)	47/49 (95.9)	0.68	35/38 (92.1)	31/33 (93.9)	1.00

Data are presented as number/number (%)..

STT, standard triple therapy; BQT, bismuth-quadruple therapy; ITT, intention-to-treat; CI, confidence interval; PP, per-protocol..

The eradication rate was not related to the types of point mutation regardless of the treatment duration in the BQT. PP data for patients harboring H. pylori with the A2143G mutation type revealed that the eradication rate at 7 days and 14 days was 90.6% (95% CI, 78.1% to 100%) and 90.0% (95% CI, 80.0% to 100%), respectively (Table 3).

Table 3 . Helicobacter pylori Eradication Rates for Bismuth-Quadruple Therapy with H. pylori with 23S Ribosomal RNA Point Mutations.

23S ribosomal RNA point mutation	ITT analysis				PP analysis
	7-day (n=42)	14-day (n=34)	p-value		7-day (n=35)	14-day (n=31)	p-value
A2142G	3/3 (100)	1/1 (100)	NA		3/3 (100)	1/1 (100)	NA
A2143G	29/39 (74.4)	27/33 (81.8)	0.45		29/32 (90.6)	27/30 (90.0)	1.00
95% CI, %	59.0–87.2	66.7–93.9			78.1–100	80.0–100

Data are presented as number/number (%)..

ITT, intention-to-treat; PP, per-protocol; CI, confidence interval; NA, not available..

3. Adverse events

In this study, severe adverse events occurred in only four patients, with the number of patients affected representing less than 5% of their respective groups. Minor adverse events were more common (greater than 50% in each group), but there was no significant difference in the prevalence of these events between the 7-day and 14-day cohorts for each treatment group (Table 4). The most common adverse effects were bitter taste (in the STT groups) and nausea/vomiting and weakness/fatigue sense (in the BQT groups).

Table 4 . Adverse Effects Associated with STT and BQT Therapies for Each Duration.

Variable	STT 7 (n=52)	STT 14 (n=49)	p-value	BQT 7 (n=38)	BQT 14 (n=33)	p-value
Total	32 (61.5)	26 (53.1)	0.39	29 (76.3)	19 (57.6)	0.09
Major	2 (3.8)*	0	0.50	1 (2.6)†	1 (3.0)‡	1.00
Minor	30 (57.7)	26 (53.1)	0.64	28 (73.7)	18 (54.5)	0.09
Specific adverse events
Bitter taste	24 (46.2)	16 (32.7)		0	0
Nausea or vomiting	6 (11.5)	2 (4.1)		13 (34.2)	10 (30.3)
Dyspepsia or bloating	3 (5.8)	1 (2.0)		1 (2.6)	6 (18.2)
Loose stool	7 (13.5)	5 (10.2)		2 (5.3)	0
Headache	6 (11.5)	1 (2.0)		0	1 (3.0)
Weakness or fatigue	4 (7.7)	1 (2.0)		22 (57.9)	8 (24.2)
Miscellaneous	4 (7.7)	3 (6.1)		8 (21.1)	6 (18.2)

Data are presented as number (%)..

STT, standard triple therapy; BQT, bismuth-quadruple therapy..

Major adverse effects that caused discontinued treatment: *One with severe nausea and the other with bitter taste, loose stool, headache, fatigue, and diaphoresis; †Severe bloating; ‡Severe nausea and vomiting..

With the exception of treatment noncompliance, clarithromycin resistance is the most important factor that adversely affects H. pylori eradication rate using first-line therapy. In this study, the proportion of clarithromycin-resistant H. pylori was 41.3%, which is roughly comparable to that reported in recent Korean studies.^7,8

Two recent Korean studies, based upon bacterial culture, and minimal inhibitory concentration (MIC) data, revealed that the prevalence of primary clarithromycin-resistant H. pylori isolates increased from 21.2%, in 2003–2005, to 45.9% in 2017–2018⁷ and that, in samples collected between 2017 and 2018, 17.8% of participants harbored clarithromycin-resistant H. pylori.⁹ Our study used DPO-PCR, rather than MIC data to confirm the clarithromycin resistance. This methodological difference and the time lag to 2020 could explain the discrepancy in the clarithromycin resistance rates determined in our study compared with previous studies using MIC. Although the combination of bacterial culture, antibiotic susceptibility tests, and MIC determination is the best way to select antibiotics for the treatment of H. pylori infections,^10,11 the difficulty in culturing H. pylori and the time-consuming nature of these processes mean that they cannot be employed easily in clinical practice. By contrast, PCR or sequencing, which detect point mutations in H. pylori 23S ribosomal RNA, known to be related to clarithromycin resistance, can be used relatively easily in clinical practice. These molecular techniques are known to have higher sensitivity than MIC after culture for detecting clarithromycin resistance.¹² For example, a recent study reported that a molecular PCR test detected clarithromycin resistance in up to 98% of clarithromycin-resistant subjects, whereas culture had only a 60% detection rate.¹³ A Korean study using DPO-PCR reported a H. pylori clarithromycin resistance rate of 37.7% during 2014 to 2019, which is very similar to the results of our study.⁸

In Korea, from 2015 to 2017, PP analysis revealed that the H. pylori eradication rate associated with empirical 14-day STT was 78.6%,¹⁴ suggesting that this approach was no longer effective as a first-line therapy. Clarithromycin resistance has gradually increased over the past decades in Korea, and it is estimated that the current eradication rate of empirical STT is well below 80%.^1,2 The Maastricht V guidelines conditionally recommend that empirical STT without a clarithromycin resistance test should be abandoned in regions where the clarithromycin resistance rate is more than 15%.¹⁵ As a consequence of the relatively low eradication rate of empirical STT and the high H. pylori clarithromycin resistance rate seen in Korea, new strategies for the treatment of H. pylori infection have been proposed. Recently, an eradication regimen based on clarithromycin susceptibility testing has been strongly suggested.^4,16

In this study, the overall H. pylori eradication rate using tailored STT, in patients with clarithromycin susceptible isolates (as determined by DPO-PCR), was 88.4% for the PP cohort. This result is comparable with previous studies, which showed an eradication rate close to 90% of eradication rates in STT without clarithromycin resistance.^17-20 In a randomized controlled trial conducted in Korea, PP analysis of a tailored 7-day STT (involving patients with clarithromycin susceptible H. pylori, based on DPO-PCR) showed a higher eradication rate than either an empirical 7-day STT or a 7-day triple therapy in which clarithromycin was replaced by metronidazole (proton pump inhibitor + amoxicillin + metronidazole, PAM) when 23S ribosomal RNA mutations were detected (91.2% vs 75.9% or 79.1%, p<0.001 for both comparisons).¹⁷ Two retrospective observational studies have investigated the efficacy of the PCR based tailored therapy in Korea. One study showed that tailored therapies, informed by DPO-PCR susceptibility testing (STT with clarithromycin susceptibility, and BQT or PAM with clarithromycin resistance), achieved higher successful eradication (91.8%) than empirical STT (72.1%, p<0.01) as first-line therapies.¹⁸ In another study, PP analysis identified that 7-day tailored therapies (STT or BQT based on clarithromycin resistance) had higher H. pylori eradication rates than an empirical 7-day STT (92.7% vs 76.5%, p=0.001).¹⁹ Tailored STT, based on DPO-PCR results, can improve H. pylori eradication rates compared with empirical STT.

The current study also showed that, as a first-line therapy in patients with clarithromycin-resistant H. pylori, the overall eradication rate of BQT was 90.9%. To date, consensus on the first-line treatment for patients with clarithromycin-resistant H. pylori has not been established. For these patients, PAM or BQT may be considered as a first-line therapy. However, in Korea, the eradication rate for 7 days PAM is only between 66.2% and 79.1%, which is not satisfactory for a first-line therapy.^17,18,20 PP analysis from one recent randomized controlled trial, in Korea, showed that 14-day BQT achieved higher clarithromycin-resistant H. pylori eradication than 14-day PAM as a first-line therapy (95.1% vs 76.4%, p=0.001).²¹ A study in China, where H. pylori clarithromycin resistance is high, reported that tailored 10-day BQT (as informed by DPO-PCR results) had a higher eradication rate of 93.4%, based on PP analysis.²² Therefore, in the presence of clarithromycin resistance, BQT appears to be a good alternative treatment option.

In this study, the overall eradication rates of tailored STT and BQT, based on DPO-PCR results, were 88.4% and 90.9%, respectively, with no significant differences in eradication rate between the two regimens. Therefore, our study suggests that tailored H. pylori eradication, informed by PCR or sequencing data, is effective as a first-line therapy, particularly in areas with prevalent H. pylori clarithromycin resistance. In addition, considering the adverse effects of taking multiple antibiotic drugs, the increasing incidence of antibiotic resistance, and few rescue therapies for H. pylori eradication, tailored therapies based on DPO-PCR may be a more reasonable therapeutic approach than empirical treatment. Furthermore, several studies in Korea have already suggested that tailored therapies have comparable cost-effectiveness compared to empirical therapies.^18,19,23 However, there is less clarity regarding the effective treatment duration when tailored STT or BQT are used as first-line regimens. If a shorter treatment period of 7 days using tailored therapies can achieve similar eradication rates compared with 14 days, there will be significant benefits in terms of cost-effectiveness, treatment duration, and reduction in antibiotic resistance. In our study, there was no significant difference in H. pylori eradication rate between the 7-day treatment group and the 14-day treatment group, following tailored STT informed by DPO-PCR ClaR data. The same was also seen for the tailored BQT regimen. Although it was anticipated that a 7-day tailored STT would be sufficiently effective for H. pylori eradication, based on the findings of several previous studies,^17-19 our study also showed that 14-day treatment had no additional benefit in those receiving tailored STT. To the best of our knowledge, there is only one other published study that has evaluated the duration of treatment for tailored BQT. In that retrospective study, in Korea, tailored BQT of either 7-day or 14-day treatment durations did not give significantly different H. pylori eradication efficiencies based on PP analysis (90.3% vs 100%, p=0.206).⁸ This is consistent with the results of our study, which showed that, like tailored STT, there was no statistical difference in the eradication rate between the 7-day and 14-day treatment periods in the tailored BQT. The results of both these studies suggest, therefore, that 7-day treatment duration is sufficient in tailored BQT.

Interestingly, the similarly high eradication rate for the 7-day and 14-day treatment periods of tailored BQT did not appear to be affected by the nature of 23S ribosomal RNA point mutations exhibited by clarithromycin-resistant H. pylori. In our study, most of the 23S ribosomal RNA point mutations identified were the A2143G point mutation, which is considered to be the genotype associated with a high risk of H. pylori eradication failure in empirical STT.²⁴ In this study, 94.7% of the clarithromycin-resistant H. pylori harbored the A2143G point mutation, which is consistent with the prevalence reported in previous studies conducted in Korea.^8,17,25,26 Although a previous retrospective study in Korea reported that 14-day BQT was superior to 7-day BQT for patients with A2143G mutations (81.9% vs 100%, p=0.024),⁸ it is necessary to investigate this through a prospective study with a larger sample size in the future.

This study has several limitations. First, it is a retrospective study conducted in single tertiary center and has a relatively small sample size. Therefore, there is a possibility of inadvertent selection bias. For example, the mean age of the 14-day BQT group was significantly younger than that of the 7-day BQT group. It is presumed that a shorter dosing period was preferred in the elderly because of concerns about adverse effects. In addition, since this study is a retrospective study rather than a protocol-following controlled trial, it would be better to consider that the PP analysis shows the more appropriate characteristics and results of this study than the ITT analysis. Second, the overall eradication rate of the tailored STT group in this study was 88.4%, which was close to 90%, but relatively lower than the previous studies that showed more than 90% eradication rates. DPO-PCR can detect only A2142G and A2143G point mutations of the 23S ribosomal RNA gene that are considered to be the main cause of clarithromycin resistance.¹⁶ However, there may be several factors other than A2142G and A2143G point mutations that affect the eradication rate in the STT group. There is a possibility that other clinically significant point mutations exist, such as A2142C, A2143C, and A2144G, that are not currently detected by DPO-PCR,²¹ although these mutations alone are associated with less than 5% of clarithromycin-resistant H. pylori isolates in Korea.^21,27 Due to the common heterogeneity of H. pylori, even within one individual,²⁸ the tissue biopsy-based DPO-PCR has the inherent potential bias of false-negative results, which may contribute to treatment failures. In addition, different individual CYP2C9 polymorphism that affects the proton pump inhibitor metabolism can be considered another cause. Third, this study did not perform H. pylori culture and MIC tests for other antibiotics, such as amoxicillin, tetracycline, and metronidazole, which may affect the eradication rates. In particular, since metronidazole resistance could be partially overcome by increasing the dose and treatment duration,¹⁵ guidelines recommend 10 to 14 days of treatment in the empirical BQT. Although, there were some studies have reported that there was no difference in the eradication rates between 7-day and 10 to 14 days treatment when the BQT is used as a second-line therapy,^29,30 similar eradication rates of 7-day and 14-day tailored BQT in this study cannot be generalized without data of metronidazole resistance. In the future, further well-designed prospective randomized controlled trials, with large sample sizes, are needed to overcome these limitations.

In conclusion, 7-day STT was as effective as a 14-day therapy in the clarithromycin susceptible group, and BQT in the clarithromycin-resistant group showed similar results. There was no significant difference in the eradication rate, patient compliance, or rate of adverse events between 7-day and 14-day therapy for both the STT and BQT treatment cohorts. Therefore, this study suggests that, following DPO-PCR clarithromycin susceptibility testing, tailored 7-day therapy is as effective as 14-day therapy for the eradication of H. pylori.

This research was supported by a grant of Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HC19C0009).

B.W.K. is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Study concept and design: B.W.K. Data acquisition: S.Y.N., B.W.K. Data analysis and interpretation: S.Y.N., B.W.K. Drafting of the manuscript: S.Y.N. Critical revision of the manuscript for important intellectual content: S.Y.N., B.W.K., M.J.K., Y.C., J.S.K. Statistical analysis: S.Y.N. Study supervision: B.W.K. Approval of final manuscript: all authors.