Introduction

In regions where there is a prevalence of clarithromycin resistant strains, 2-week bismuth quadruple therapy (PBMT) is recommended as the first-line treatment. In cases where CLA resistance-related genetic mutations are identified, 1-week metronidazole triple therapy is recommended. The aim of this study is to investigate whether 1-week bismuth-added metronidazole triple therapy (PBMA) therapy can achieve equivalent efficacy to 2-week PBMT therapy.

Aims & Methods

This study was a multicentred retrospective analysis using electronic medical records, employing propensity score matching to analyze the results. The study population consisted of individuals who were confirmed to have H. pylori infection with clarithromycin resistance-associated genetic mutation (A2143G) using PCR and who were administered either 2-weeks PBMT or 1 week PBMA.

Results

From October 2019 to May 2023, a total of 121 patients were confirmed for H. pylori infection and clarithromycin resistance-related genetic mutations using PCR. Among them, 6 patients with the A2142G mutation were excluded, leaving 115 patients with the A2143G mutation for analysis. Out of these 115 patients, retrospective analysis was conducted on 82 patients who underwent UBT testing at least 4 weeks after completing the antibiotic regimen and had complete medical records.
Among the 82 patients analyzed, 51 had received the conventional 2-week PBMT while 31 had received a 1-week PBMA. Propensity score matching was performed for gender, age, and body mass index, factors suspected to influence the efficacy of eradication, resulting in 25 matched cases in each group.
The baseline characteristics, including age and gender distributions, did not differ significantly between the two groups of analyzed subjects.
The efficacy of eradication therapy was confirmed through UBT conducted 4-8 weeks after treatment. In the analysis before propensity score matching (PSM), the eradication rates for the 2-week PBMT group and the 1-week PBMA group were 70.6% and 77.4% in the intention-to-treat (ITT) analysis, respectively, and 94.7% and 85.7% in the per-protocol (PP) analysis, respectively. There was no significant difference between the two groups in both analyses.
After PSM, the analysis still showed no significant difference between the 2-week PBMT group and the 1-week PBMA group. In the ITT analysis, the eradication rates were 68.0% for the OBMT2w group and 80.0% for the OAM+B1w group, while in the PP analysis, the rates were 94.4% for the OBMT2w group and 87.0% for the OAM+B1w group.
Regarding adverse events, there was no difference in the frequency of adverse events between the two groups. However, the need to discontinue medication occurred in 5.3-5.6% of cases in the 2-week PBMT group but did not occur in the 1-week PBMA group. Nonetheless, changes in bowel habits were more common in the 1-week PBMA group, with the main reason being a change to dark-colored stool.

Conclusion

For patients infected with H. pylori carrying the A2143G point mutation, there was no difference in the eradication rate between the 2-week PBMT regimen and the 1-week PBMA regimen. The 1-week PBMA regimen showed superior drug compliance and a tendency for fewer adverse effects compared to the 2-week PBMT regimen.

References

1. Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut 2022;71:1724-1762.
2. Jung HK, Kang SJ, Lee YC, et al. Evidence-Based Guidelines for the Treatment of Helicobacter pylori Infection in Korea 2020. Gut Liver 2021;15:168-195.
3. Seo SI, Lim H, Bang CS, et al. Bismuth-Based Quadruple Therapy versus Metronidazole-Intensified Triple Therapy as a First-Line Treatment for Clarithromycin-Resistant Helicobacter pylori Infection: A Multicenter Randomized Controlled Trial. Gut Liver 2022;16:697-705.
4. Moon SG, Lim CH, Kang HJ, et al. Seven Days of Bismuth-Based Quadruple Therapy Is as Effective for the First-Line Treatment of Clarithromycin-Resistant Confirmed Helicobacter pylori Infection as 14 Days of Bismuth-Based Quadruple Therapy. J Clin Med 2022;11.
5. Bang CS, Lim H, Jeong HM, et al. Amoxicillin or tetracycline in bismuth-containing quadruple therapy as first-line treatment for Helicobacter pylori infection. Gut Microbes 2020;11:1314-1323

Disclosure

​Authors have ​nothing to disclosure.

Introduction

Helicobacter pylori is a common cause of peptic ulcers and gastritis. Standard triple therapy includes a PPI with amoxicillin and either clarithromycin or levofloxacin. Rising antibiotic resistance has reduced its effectiveness. Sequential therapy offers a phased alternative with better outcomes in resistant cases.

Aims & Methods

To evaluate and compare the efficacy of clarithromycin and levofloxacin-based triple and sequential therapies for Helicobacter pylori (H. pylori) eradication in a resource-limited setting, in the context of emerging antibiotic resistance.
A prospective, randomized study was conducted at a tertiary care center from January 1, 2022, to January 1, 2025. A total of 300 treatment-naïve patients aged 18–60 years, diagnosed with H. pylori infection through stool antigen, urea breath test, or histology, were included. Patients with prior eradication therapy or recent antibiotic use were excluded. Participants were randomized into four equal groups (n=75 each):

• Clarithromycin-based triple therapy (amoxicillin, clarithromycin, PPI)
• Levofloxacin-based triple therapy (amoxicillin, levofloxacin, PPI)
• Clarithromycin-based sequential therapy (amoxicillin + PPI for 5 days, followed by clarithromycin + tinidazole + PPI for 5 days)
• Levofloxacin-based sequential therapy (amoxicillin + PPI for 5 days, followed by levofloxacin + tinidazole + PPI for 5 days) Therapeutic response was assessed post-treatment for eradication.
  

Results

Out of 300 patients (180 males, 120 females), eradication was achieved in:

• 48/75 (64%) in clarithromycin-based triple therapy
• 53/75 (70.7%) in levofloxacin-based triple therapy
• 51/75 (68%) in clarithromycin-based sequential therapy
• 61/75 (81.3%) in levofloxacin-based sequential therapy

All patients completed therapy without notable adverse events or compliance issues. Lower eradication rates in clarithromycin-based regimens suggest rising resistance.

Conclusion

Levofloxacin-based sequential therapy demonstrated the highest eradication rate, highlighting its potential as a preferred regimen in settings with rising clarithromycin resistance. Clarithromycin-based treatments showed suboptimal outcomes, emphasizing the need for region-specific antibiotic stewardship and resistance surveillance.

References

1. Kim JS, Kim BW, Hong SJ, Kim JI, Shim KN, Kim JH, Baik GH, Kim SW, Song HJ, Kim JH. Sequential Therapy versus Triple Therapy for the First Line Treatment of Helicobacter pylori in Korea: A Nationwide Randomized Trial. Gut Liver. 2016 Jul 15;10(4):556-61. doi: 10.5009/gnl15470. PMID: 27114421; PMCID: PMC4933415.
2. Chang, J.Y., Shim, KN., Tae, C.H. et al. Triple therapy versus sequential therapy for the first-line Helicobacter pylori eradication. BMC Gastroenterol 17, 16 (2017). https://doi.org/10.1186/s12876-017-0579-8

Introduction

Rising antimicrobial resistance has critically impaired the efficacy of standard triple therapy for Helicobacter pylori (H. pylori), especially in Latin America, where resistance to clarithromycin and metronidazole exceeds 20–30%. Bismuth-based quadruple therapy and newer potassium-competitive acid blockers (P-CABs), such as tegoprazan, offer enhanced acid suppression and pharmacological stability. Limecycline, a soluble tetracycline derivative with 5000-fold greater solubility than tetracycline, may serve as a suitable alternative where tetracycline is scarce. We aimed to evaluate the real-world efficacy and tolerability of a quadruple regimen combining limecycline, furazolidone, bismuth, and tegoprazan.

Aims & Methods

We conducted a prospective, multicentre pilot study in Lima (Peru) and Bogotá (Colombia) between January and May 2024. Adults ≥18 years with confirmed H. pylori infection by histology, rapid urease test or 13C-urea breath test (UBT-C13) were included. Participants received limecycline 300 mg, furazolidone 100 mg, bismuth subcitrate 262 mg, and tegoprazan 50 mg, all administered twice daily for 14 days. Antibiotics and acid suppressors were withheld four weeks prior to eradication testing. Eradication was assessed 6–8 weeks after therapy. Safety, adherence, and adverse events (AEs) were recorded. Results are reported with 95% confidence intervals (CI) and p-values where relevant.

Results

Seventy-two patients were enrolled (mean age: 55 [95% CI: 51–59]; range 25–83; 79% female). Of these, 56% were treatment-naïve, while 44% had failed at least one prior regimen. Per-protocol analysis showed an eradication rate of 98.6% (71/72; 95% CI: 92.6–99.9%). Only one patient discontinued due to a rash. Mild AEs were reported in 11.1% (95% CI: 5.2–20.1%), including nausea (6.9%), constipation (2.8%) and diarrhoea (1.4%). No severe events or hospitalisations occurred. The eradication rate did not significantly differ by prior treatment history (p = 0.88). This therapy achieved >95% eradication even in previously treated patients, surpassing thresholds recommended by international guidelines.

Table. Clinical Outcomes with Quadruple Therapy (n = 72)

Parameter	Value	95% CI / Additional Info
Mean age (years)	55	51–59
Female sex, n (%)	57 (79%)	68.6–87.1%
Treatment-naïve, n (%)	40 (56%)	44.4–67.1%
Prior treatment failure (≥1), n (%)	32 (44%)	32.9–55.6%
Completed full regimen, n (%)	71 (98.6%)	92.6–99.9%
Confirmed eradication, n (%)	71/72 (98.6%)	92.6–99.9%; p = NS by treatment history
Mild adverse events, n (%)	8 (11.1%)	5.2–20.1%
Discontinuation due to AE, n (%)	1 (1.4%)	0.04–7.5%
Diagnostic method for cure	UBT-C13 or histology	Post-treatment, 6–8 weeks

Conclusion

This multicentre pilot study demonstrates that the limecycline–furazolidone–bismuth–tegoprazan quadruple regimen is a highly effective and well-tolerated option for H. pylori eradication in Latin American real-world settings. A near-100% eradication rate (98.6%; 95% CI: 92.6–99.9%), including in patients with treatment failure, supports its use as both empirical first-line and salvage therapy. Limecycline emerges as a promising substitute for tetracycline, and tegoprazan offers robust acid control. These findings justify further validation in large-scale, randomised controlled trials. With this empirical quadruple therapy, we achieved eradication consistently superior to 95%.

References

• Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022;71(9):1724–1762. doi:10.1136/gutjnl-2022-327745

• Jung HK, Kim SE, Kwon KA, et al. A randomized, double-blind, controlled trial of tegoprazan-based triple therapy versus lansoprazole-based triple therapy for Helicobacter pylori eradication. Gut Liver. 2021;15(2):212–221. doi:10.5009/gnl19545

• Choi SC, Lee SY, Kim YH, et al. Efficacy of tetracycline-containing regimens as second-line treatment for Helicobacter pylori: a nationwide multicenter study in Korea. Helicobacter. 2019;24(6):e12652. doi:10.1111/hel.12652

Introduction

The efficacy of Helicobacter pylori (H. pylori) eradication regimens containing a proton pump inhibitor (PPI) plus antibiotics has gradually declined in recent years due to higher rates of antimicrobial resistance and insufficient acid inhibition. Vonoprazan (VPZ) is a novel potassium-competitive acid blocker which provides a stronger and longer-lasting effect on gastric acid suppression than PPIs. Our objective was to perform a systematic review and meta-analysis evaluating the efficacy and safety of VPZ for H. pylori eradication.

Aims & Methods

We conducted bibliographical searches in PubMed, Embase and the Cochrane Library up to April 2023. Selection: studies evaluating the use of VPZ in the eradication treatment. Outcomes: Efficacy was assessed by intention-to-treat analysis. Safety was also evaluated. Results were combined by meta-analysing risk differences (RD) and were stratified by dual, triple and quadruple therapy, first-line and rescue therapy, and by the presence of clarithromycin resistance.

Results

Overall, 75 studies were included, evaluating 44,992 patients, where 22,264 had received VPZ and 22,658 a PPI-based eradication therapy. The overall eradication rate with VPZ was 88% (95%CI=87-90%, 75 studies, I²=88%). When only RCTs were considered, similar results were obtained (87%, 95%CI=85-90%, 35 studies I²=84%).
When comparing dual, triple and quadruple VPZ-containing therapies, a tendency towards better efficacy with those regimens using a greater number of antibiotics was observed: 85%, 88% and 95%, respectively. However, when we compared the eradication rates between VPZ-based dual vs. triple regimens, no significant differences were reported, either in the overall analysis (P=0.17) or in the meta-analysis of studies directly comparing these regimens (P=0.21).
The eradication rate with VPZ-based therapy in first-line was 87% (95%CI=86-89%, 55 studies, I²=89%), and 90% (95%CI=87-93%, 37 studies, I²=84%) when used as rescue therapy. Among treatment-naïve patients, a significant superiority in the VPZ vs. PPI-based regimens was reported (87% vs. 70% respectively; RD=0.12, 95%CI=0.10-0.14, P<0.00001, I²=83%). However, no significant differences were shown between VPZ and PPIs when used in rescue therapy. When focusing on RCTs only, similar results were obtained.
Among those patients with clarithromycin-resistant strains, an overall efficacy of VPZ-based therapies was 81% (95%CI=75-85%, 18 studies, I²=60%), while in those with clarithromycin-susceptible strains it was 92% (95%CI=89-95%, 18 studies, I²=87%). We found a significant superiority of VPZ vs. PPIs (75% vs. 39%; RD=0.35, 95%CI=0.27-0.42, P<0.00001, 7 studies, 797 patients) in clarithromycin-resistant patients; whereas no significant differences were found in the clarithromycin-susceptible group. RCTs subgroup analysis showed similar results.
The overall incidence of adverse events with VPZ was 18% (95%CI=15-20%, 69 studies, I²=97%). No significant differences were found between VPZ and PPIs regimens tolerability.

Conclusion

The efficacy of VPZ-based regimens was over 85% in all treatments evaluated. The advantage of triple over dual VPZ could not be demonstrated in direct comparisons. In treatment-naïve patients as well as in those cases with clarithromycin-resistant strains, VPZ-based regimens performed better than PPIs-based ones; however, in rescue therapy and in clarithromycin-susceptible patients, this advantage was not confirmed. Tolerability was similar in both VPZ and PPIs regimens.

Disclosure

Dr. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen. Dr. Nyssen has received research funding from Mayoly and Allergan.

Introduction

After an initial attempt to eradicate Helicobacter pylori (Hp), around 20% of patients remain infected. As treatment failures accumulate, the effectiveness of subsequent Hp therapies tends to decrease. Therefore, current clinical guidelines discourage repeated use of the same treatment regimen following an initial failure.

Aims & Methods

To evaluate the use and effectiveness of the triple therapy with amoxicillin-clarithromycin and of the bismuth quadruple therapy (either classical and as single-capsule format) when empirically prescribed as retreatment, despite previous eradication failure with the same regimen.
All patients registered at e-CRF AEG-REDCap as part of the European Registry on Hp management (Hp-EuReg) from 2013-2024, who had received triple therapy with amoxicillin-clarithromycin or bismuth quadruple therapy (either classical or as single-capsule) in at least 2 different treatment lines (not necessarily consecutive), were analysed separately.

Results

Triple therapy with amoxicillin-clarithromycin: Out of 518 patients treated with triple therapy from 2^nd to 6^th rescue treatment line, 230 cases received the same therapy at least in 2 different treatment lines: 199 re-treatments in 2^nd line having previously failed in 1^st line with this therapy; 19 re-treatments in 3^rd line (of which 9 had previously received the same therapy only in the 1^st line and 10 had received the same therapy in both 1^st and 2^nd line); 4 in 4^th line; 5 in 5^th line; and further 3 in 6^th line. The overall effectiveness of triple therapy with amoxicillin-clarithromycin when empirically prescribed repeatedly in 2^nd line was 74%. When the effectiveness was subanalysed by treatment length, there were increasing efficacy rates according to it: 50% with 7 days, 72% with 10 days, and 82% with 14 days. The cases retreated in 3^rd line had an overall effectiveness of 56%.
Bismuth quadruple classical therapy: Out of 672 patients treated with bismuth quadruple classical therapy from 2^nd to 6^th rescue treatment line, 13 cases received the same therapy at least in 2 different treatment lines: 6 re-treatments in 2^nd line, having previously failed in 1^st line; 2 re-treatments in 3^rd line, both had previously received the same therapy in 2^nd line; 2 in 4^th line; 1 in 5^th line; and further 2 in 6^th line. The effectiveness of bismuth quadruple classical therapy when empirically prescribed repeatedly in the 2^nd line was 69%, although the number of patients in this cohort was limited.
Bismuth quadruple therapy as single-capsule: Out of 2,579 patients treated with the single-capsule from 2^nd to 6^th rescue treatment line, 101 cases received the same therapy at least in 2 different treatment lines: 67 re-treatments in 2^nd line having previously failed in 1^st line with the single-capsule; 16 re-treatments in 3^rd line, of which 12 had previously received this same therapy in 2^nd line; 11 in 4^th line; 4 in 5^th line; and further 3 in 6^th line. The effectiveness of bismuth quadruple therapy as single-capsule when empirically prescribed repeatedly in 2^nd line was over 90%, and achieved almost 80% in all cases retreated in the 3^rd line.

Conclusion

Repeated use of triple therapy with amoxicillin-clarithromycin in patients with prior eradication failures with the same regimen demonstrated notable success rates, particularly in 2^nd line re-treatments lasting 14 days (>80%). On the other hand, bismuth quadruple therapy as single-capsule, when prescribed as re-treatment in 2^nd line after previous failure with the same therapy, achieved optimal effectiveness (>90%).

References

1. Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022;71(9):1724–62.
2. Nyssen OP, Vaira D, Pérez Aísa Á, Rodrigo L, Castro-Fernandez M, Jonaitis L, et al. Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg). Clin Gastroenterol Hepatol. 2022;20(10):2243–57.

Disclosure

Olga P. Nyssen has served as a speaker or has received research funding from Allergan, Mayoly Spindler, Richen, Biocodex and Juvisé.
Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé, Biocodex.
The remaining authors declare no conflicts of interest.

Introduction

Global rise in primary Helicobacter pylori (H. pylori) antibiotic resistance has led to a decrease in the treatment efficacy. Understanding the rates of clarithromycin (ClaR), metronidazole (MetR) and levofloxacin (LevR) resistance in H. pylori management is essential for determining the optimal eradication therapy and achieving successful clinical outcomes.

Aims & Methods

To evaluate the prevalence and geographical distribution of H. pylori primary ClaR, MetR and LevR in Europe. Bibliographical searches were conducted in PubMed until March 2024, with no language restrictions. Studies focused on children only or non-European countries were excluded.

Results

A total of 218 studies published since 1990 were included, of which 188 provided information on ClaR, 138 on MetR, and 77 on LevR (Table 1). The average ClaR in Europe, considering all studies and years, was 17%, showing an increase from 7.3% in the 1990s to 26% in the period 2010–2019, with a slight decrease to 22% in the period 2020–2024. The highest values were reported in Switzerland (66%), Ireland (50%), and Israel (44%). Southern European countries presented higher resistance rates (over 15–20%) compared to those in the north (under 10–15%). MetR remained consistently high (with a European average of 34%), particularly in Poland (66%), Turkey (67%), and Switzerland (60%). As for LevR, it was low in the 1990s but experienced a progressive increase over time, reaching approximately 15% during 2010–2019, and fluctuating between 20% and 25% in recent years.

Table 1. Clarithromycin, metronidazole and levofloxacin primary resistance prevalence in Europe in the last four decades (1990-2024).

Clarithromycin % (n/N)

Metronidazole % (n/N)

Levofloxacin % (n/N)

Country

1990-1999

2000-2009

2010-2019

2020-2023

1990-1999

2000-2009

2010-2019

2020-2023

1990-1999

2000-2009

2010-2019

2020-2023

Armenia ​Austria ​Belgium ​Bosnia and Herzegovina ​Bulgaria ​Croatia ​Denmark ​Estonia ​Finland ​France ​Germany ​Greece ​Hungary ​Iceland ​Ireland ​Israel ​Italy ​Lithuania ​Netherlands ​Norway ​Poland ​Portugal ​Romania ​Russia ​Scotland ​Serbia ​Slovenia ​Spain ​Sweden ​Switzerland ​Turkey ​United Kingdom

NA 3.3 (11/331) 6.9 (436/6369) NA 9.4 (37/390) NA NA 2.8 (3/106) NA 24.7 (78/314) 2.8 (52/2143) 30 (15/50) NA NA 4.4 (25/557) NA 10.7 (115/1076) 1.1 (1/89) 1.6 (31/2016) NA 9.1 (6/66) 13.4 (90/672) NA NA 1.8 (3/162) NA NA 8.2 (130/1587) 2.2 (10/442) 27 (77/286) NA 6.2 (26/415)

NA 17 (76/448) 11.3 (493/4340) NA 18.1 (61/338) 17.7 (245/1390) 7.4 (6/81) 3.3 (3/90) 8.1 (108/1329) 24.2 (599/2474) 4.9 (99/2005) NA 17.3 (41/238) NA 12.7 (19/148) 8.2 (9/110) 18.1 (463/1076) 3.5 (6/171) 5.9 (46/778) 5.9 (6/102) 19.1 (58/303) NA NA 7.7 (86/1111) NA NA NA 19.8 (1205/6075) 1 (2/205) 50.9 (28/55) 29.2 (179/612) 13.8 (505/3656)

3.6 (2/55) 24.6 (57/232) 18.2 (1362/7467) NA 21.7 (124/569) 21.1 (73/345) NA NA NA 19.9 (233/1167) 13.3 (350/2624) 33.9 (65/192) NA 9 (9/105) 50.5 (53/105) 48.9 (355/726) 25.6 (1681/6567) 8.2 (5/67) 10.5 (80/757) 9.5 (4/42) 32.9 (71/216) 32.2 (47/145) 20 (18/90) 8.7 (15/170) NA NA 14.3 (8/56) 17.1 (2695/15711) NA 66.3 (143/216) 27.6 (206/746) 28.7 (77/268)

NA NA 18.9 (51/269) 28.3 (13/46) 30 (15/50) NA NA NA NA NA NA NA NA NA NA 43.8 (14/32) 21 (49/231) NA 47 (280/596) NA NA NA NA NA NA 24.1 (68/283) NA 13.7 (176/1283) NA NA 33.4 (31/94) NA

NA 31.6 (104/330) 29.3 (4236/14448) NA 30.2 (133/440) NA NA 43 (144/336) 25.6 (22/86) 43.7 (28/64) 25.4 (533/2094) NA NA NA 35.7 (199/557) NA 19.7 (145/736) 24.7 (22/89) 18.1 (503/2787) NA 54.5 (60/110) 30.6 (248/810) NA NA NA NA NA 25.7 (408/1587) 27.4 (121/442) 50.7 (343/675) NA 32.8 (1132/3447)

NA NA 30.9 (1343/4340) NA 26.3 (488/1857) 23.3 (303/1301) 40.2 (49/123) 49.2 (80/162) 40.6 (539/1329) 46.9 (1101/2348) 26.4 (536/2026) NA NA NA 28.9 (43/148) 38.2 (42/110) 34.3 (486/1418) 34.5 (59/171) 13.7 (105/769) 22.5 (23/102) 45.3 (137/303) NA NA 31.4 (349/1111) NA NA NA 38.3 (2282/5957) 76 (156/205) 60.5 (33/55) 43.3 (77/178) 33.6 (1229/3656)

NA 10.2 (13/128) 35.7 (2293/6428) NA 35.2 (200/569) 10.2 (35/345) NA NA NA 50.7 (511/1007) 29.7 (71/240) 31.1 (42/135) NA 1 (1/105) NA 20.2 (147/726) 40.8 (2553/6257) 32.8 (22/67) 13.6 (102/752) 38.1 (16/42) 66.1 (143/216) 48.2 (70/145) NA 41.6 (71/170) NA NA NA 34.5 (2390/5957) NA NA 42.6 (160/374) 55.8 (150/268)

NA NA 53.9 (145/269) NA 48 (24/50) NA NA NA NA NA NA NA NA NA NA 31.3 (10/32) 18.8 (18/96) NA 46 (274/596) NA NA NA NA NA NA NA NA 23.8 (305/1283) NA NA 67.2 (41/61) NA

NA NA NA NA NA NA NA NA NA NA NA 0 (0/50) NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 10.2 (150/1475) NA NA NA NA

NA 12 (37/310) NA NA NA NA NA NA 7 (72/1037) 14.1 (267/1893) 11.7 (7/60) NA NA NA NA NA 10.8 (115/1068) NA NA NA 3.9 (13/344) NA NA 14.7 (164/1111) NA NA NA 14.7 (334/2277) NA NA 23.1 (34/147) 2.4 (1/40)

12.8 (7/55) 9.4 (12/128) 24.5 (1574/6438) NA 22.9 (131/569) 4.6 (8/175) NA NA NA 15.8 (159/1007) 14.5 (263/1816) 5.3 (3/57) NA 4 (4/105) 15.2 (16/105) 5.6 (47/843) 18.5 (1004/5432) NA 12.9 (24/185) NA 8.6 (15/174) 26.2 (38/145) 30 (27/90) 14.4 (24/170) NA NA 0 (0/56) 18.4 (1440/7813) NA 35.6 (77/216) 29.1 (134/462) 8.7 (23/268)

NA NA 26.8 (72/269) 36.9 (17/46) 38 (19/50) NA NA NA NA NA NA NA NA NA NA 18.8 (6/32) 37.8 (51/135) NA 23 (137/596) NA NA NA NA NA NA 8.3 (23/283) NA 19.3 (578/2993) NA NA 30.7 (29/94) NA

Number of patients tested for each antibiotic: n (positive resistance results)/N (total number of patients with H. pylori infection). NA: not available.

Conclusion

In Europe, since the 1990s, primary ClaR has fluctuated but always remaining above 15%; MetR has remained consistently high; and LevR has shown a progressive increase throughout the study periods. These data highlight the urgent need for region-specific antibiotic stewardship and updated treatment guidelines to ensure H. pylori eradication success.

Disclosure

Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from: Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé and Biocodex.
Olga P. Nyssen received research funding from: Mayoly, Allergan/Abbvie, Richen, Juvisé and Biocodex.

Introduction

Helicobacter pylori eradication with standard triple therapy fails in ≥20% of the cases, mainly due to bacterial antibiotic resistances. Non-bismuth quadruple concomitant therapy is among the most widely used first-line treatments against H. pylori infection, even in high clarithromycin resistance areas.

Aims & Methods

To evaluate the efficacy and safety of non-bismuth quadruple concomitant therapy (proton pump inhibitor, clarithromycin, amoxicillin and nitroimidazole) in the treatment of H. pylori infection, and to compare it with other triple and quadruple regimens.
Bibliographical searches were performed in PubMed up to April 2024. We performed a meta-analysis of the studies evaluating the concomitant therapy as a first-line regimen, and of the randomised controlled trials comparing concomitant vs. standard triple, sequential, hybrid, and bismuth quadruple therapies.

Results

115 studies (78 randomised trials) were included (23,454 patients); 39 studies compared concomitant vs triple (13,494 patients), 38 studies vs sequential (11,907 patients), 12 studies vs hybrid (3,719 patients) and 11 studies vs bismuth quadruple (3,258 patients). Concomitant regimen achieved an overall eradication rate of 86% (95%CI=85-86%) by intention-to-treat, and 90% (90-91%) by per-protocol. Concomitant therapy achieved high eradication rates even in single clarithromycin resistant (89%) and metronidazole resistant (95%) patients, but poor cure rates in dual (clarithromycin and metronidazole) resistance (68%). The overall efficacy by intention-to-treat with concomitant therapy was significantly higher as compared to both triple therapy (risk difference [RD]=0.11; 95%CI=0.09-0.14; 39 studies) and sequential therapy (RD=0.04; 0.02-0.06; 38 studies); however, in the latter comparison, when only 14-day prescriptions were considered, no significant differences were observed (RD=0.01; -0.05-0.06; 4 studies). Likewise, the overall efficacy of concomitant therapy was similar to hybrid (RD=0.01; -0.01-0.03; 12 studies), and to bismuth quadruple therapy (encompassing the classical form and the single-capsule (RD=0.01; -0.03, 0.06; 11 studies). The overall incidence of adverse events with concomitant therapy was 37% (36-38%) (85 studies). When comparing only the studies with the same treatment durations, the incidence of adverse events with concomitant therapy was similar to that of triple (RD=0.04; -0.01-0.09; 15 studies), sequential (RD=0.03; -0.00-0.06; 16 studies), and bismuth quadruple therapies (RD=0.02; -0.06-0.09; 7 studies), but higher than that of hybrid therapies (RD=0.10; 0.04-0.15; 7 studies).

Conclusion

Non-bismuth quadruple concomitant therapy is highly effective for H. pylori eradication (achieving a cure rate of approximately 90%), even in the presence of clarithromycin or metronidazole resistance, being superior to standard triple and sequential therapies, and similar to hybrid and bismuth quadruple regimens. The incidence of adverse events with concomitant treatment is relatively high (37%), similar to that of triple and bismuth quadruple regimens.

Disclosure

Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from: Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé and Biocodex.
Olga P. Nyssen received research funding from: Mayoly, Allergan/Abbvie, Richen, Juvisé and Biocodex.