Clinical Effectiveness of Penicillin-Free Therapies in First-Line and Rescue Treatments for Helicobacter pylori: A Systematic Review
Abstract
:1. Introduction
2. Methods
2.1. Search Strategy
2.2. Study Selection
- Inclusion criteria:
- Study design: Prospective, retrospective, cross-sectional, or case-control studies.
- Language: Studies written in English only.
- Participants:
- All age groups, regardless of gender.
- Patients diagnosed with H. pylori infection, with or without penicillin allergy.
- Intervention:
- First-line and/or rescue therapies.
- Regimens using combinations of antimicrobial agents.
- Penicillin-free regimens.
- Studies involving clinical trials.
- Outcome: Studies reporting on the effectiveness of H. pylori eradication therapy.
- Exclusion criteria:
- Study design: Non-eligible publication types such as review articles, systematic reviews, or meta-analyses.
- Intervention:
- Regimens without antibiotic combinations (i.e., monotherapies).
- Studies evaluating only penicillin-containing therapies.
- Studies without clinical trials (e.g., in vitro or animal research).
- Outcome: Studies not reporting the effectiveness of H. pylori eradication therapy or studies reporting only on the efficacy of probiotics.
- Duplicate records.
- Data Extraction
- The extracted data included the following:
- Study characteristics: study name, year of publication, study type, and country.
- Participant characteristics: participant age, number of subjects enrolled, and prevalence of penicillin allergy.
- Intervention characteristics: H. pylori eradication regimens including drugs, dosages, treatment duration, and eradication rates based on both intention-to-treat (ITT) and per-protocol (PP) analyses.
- Diagnostic methods used to detect H. pylori infection.
- Risk of Bias
3. Results
3.1. Literature Search
3.2. Characteristics of the Included Studies
3.3. Interventions—Protocols of Treatment
3.4. H. pylori Detection Methods
3.5. Risk of Bias Assessment
3.6. Tolerability and Compliance
4. Discussion
- Adding bismuth to the regimen, significantly increasing eradication rates.
- Extending treatment to 14 days, provided H. pylori is sensitive to clarithromycin and metronidazole.
- Increasing metronidazole dosage, though this may reduce adherence due to side effects.
- Substituting PPIs with vonoprazan, a novel acid suppressant that has shown promising results but is not yet available in all countries.
- Eight studies had a moderate risk of bias, meaning their results are useful but should be interpreted cautiously due to some methodological limitations.
- One study was classified as high risk, with significant methodological issues that may compromise the reliability of its conclusions.
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Appendix A. Summary of Risk of Bias Assessment for Included Studies
Study ID | Study Type | Selection Bias | Justification | Measurement Bias | Justification | Confounding Bias | Justification | Overall Risk |
[14] | Randomized controlled trial | Low | Randomized groups ensure comparability | Low | Objective outcome measure (urea breath test) | Low | Confounders considered, compliance assessed | Low |
[15] | Retrospective | Moderate | Not randomized, selection bias possible due to patient selection. | Low | 13C-UBT breath test is a reliable outcome measure. | Moderate | Small sample size (n = 53), potential confounders not fully controlled. | Moderate |
[16] | RCT | Low | Randomized multicenter trial reduces selection bias. | Low | Objective measures (eradication rates, ulcer healing). | Low | Balanced groups, no major confounders noted. | Low |
[17] | Case Report | High | Single-patient case, no randomization. | Moderate | Use of agar dilution susceptibility testing ensures reliability, but single case limits generalizability. | High | No control group, high risk of confounding. | High |
[18] | Prospective Intervention | Moderate | Small sample size (n = 17), limited generalizability. | Low | Objective measures used for eradication confirmation. | Moderate | Lack of control group increases confounding risk. | Moderate |
[19] | RCT | Low | Randomized trial comparing AST-guided therapy vs. Pylera®. | Low | Objective outcome measure (fecal antigen test). | Low | Balanced groups, adherence and side effects analyzed. | Low |
[12] | Prospective Cohort | Moderate | Not randomized, selection bias possible. | Low | Objective microbiome analysis via 16S rRNA gene sequencing. | Moderate | No control over external factors affecting microbiome. | Moderate |
[20] | Randomized controlled trial | Moderate | No mention of allocation concealment, which could lead to selection bias. | Low | The E-test method for antimicrobial susceptibility is a standard and reliable measurement. | Low | Randomization controls confounding factors, and the populations were comparable. | Low |
[21] | Registry-based study | Moderate | No randomization, potential for selection bias in choosing patients from the registry. | Low | The methodology and efficacy outcomes were well-defined, with good validation of the treatments. | Low | The large sample size and use of standard treatment regimens minimize confounding. | Moderate |
[22] | Randomized controlled trial | Moderate | No mention of allocation concealment or blinding, which could lead to selection bias. | Low | The 13C-UBT breath test was used, which is a standard and reliable method for H. pylori eradication assessment. | Low | Randomization was performed, and baseline characteristics are similar, minimizing confounding. | Low |
[23] | Cohort study | Moderate | No mention of randomization or allocation concealment, which could lead to selection bias. | Low | Urea breath test was used to confirm H. pylori eradication, which is reliable. | Low | The study does not have confounding variables since it is well controlled with penicillin allergy as the main criterion. | Low |
[11] | Randomized controlled trial | Moderate | No mention of allocation concealment, which could lead to selection bias. | Low | 13C-UBT breath test was used, which is a reliable measure for H. pylori eradication. | Low | Randomization is performed, and the two groups are comparable, minimizing confounding. | Low |
[24] | Prospective observational study | Moderate | Small sample size (20 patients) may lead to selection bias. | Low | 13C-UBT breath test is a reliable measure for H. pylori eradication. | Low | Random assignment of patients to VPZ-based and PPI-based regimens, minimizing confounding. | Low |
[25] | Cohort study | Moderate | No randomization, and patients were not equally distributed between resistant and non-resistant groups. | Low | The use of 13C-UBT breath test and stool antigen test is reliable for confirming eradication. | Low | Resistance to antibiotics (sitafloxacin and metronidazole) could be a confounder, but the study adjusts for this. | Moderate |
[26] | Retrospective cohort study | Moderate | Retrospective design may lead to selection bias. | Low | 13C-UBT breath test is a reliable method for determining eradication success. | Low | The study considered different regimens and analyzed intention-to-treat vs. per-protocol outcomes, minimizing confounding. | Moderate |
[27] | Randomized controlled trial | Low | Randomization of patients into 3 groups reduces selection bias. | Low | Standardized methodologies for measuring eradication and evaluating side effects. | Low | Randomization and large sample size minimize potential confounders. | Low |
[28] | Cohort study | Moderate | No randomization, but a large sample size (650 patients) reduces selection bias. | Low | Serum PG I/II ratios were measured before and after treatment, which is reliable. | Low | No significant confounders mentioned, but the study acknowledges variations in treatment regimens. | Low |
[29] | Randomized controlled trial | Low | Randomization reduces selection bias. | Low | Use of antimicrobial susceptibility testing and standardized eradication protocols. | Low | Randomization minimizes confounding. The study accounts for resistance factors. | Low |
[4] | Prospective multicenter | Low | Consecutive patients were included, reducing the likelihood of selection bias. | Low | The use of 13C-UBT is objective and reliable for measuring eradication. | Low | No major confounders were identified; treatment regimens were standardized. | Low |
[30] | Prospective multicenter | Low | 28 consecutive patients were treated, reducing bias in selection. | Low | 13C-UBT is used for accurate measurement of eradication. | Low | The study clearly focused on penicillin-allergic patients with standardized treatment regimens. | Low |
[31] | Observational cohort | Moderate | Patients who failed previous treatments were included, potentially creating a selection bias. | Moderate | Pre-antibiotic sensitivity testing can lead to misclassification of resistance. | Moderate | Resistance to clarithromycin and metronidazole could influence results, especially in resistant strains. | Moderate |
[32] | Prospective multicenter | Low | Consecutive patients with penicillin allergy were included, minimizing selection bias. | Low | 13C-UBT is reliable for eradication assessment. | Low | No significant confounding factors were identified; treatment regimens were carefully managed. | Low |
[33] | Randomized controlled trial | Moderate | Randomization was performed, but may have overlooked some baseline differences. | Moderate | Eradication was measured, but the distinction between metronidazole-sensitive and resistant strains could introduce some bias. | Moderate | The use of metronidazole and amoxicillin can be affected by resistance patterns, introducing potential confounding. | Moderate |
[34] | Observational cohort | Low | Patients were treated consecutively, minimizing selection bias. | Low | HP eradication was tested using reliable methods, reducing measurement bias. | Low | No significant confounders were identified in the analysis, and treatment regimens were standardized. | Low |
[35] | Prospective single-center | Low | Consecutive patients with penicillin allergy were included, reducing selection bias. | Low | 13C-UBT used for measuring eradication is accurate and reliable. | Low | No significant confounders identified; therapies were well-defined and standardized. | Low |
[36] | Prospective single-center | Low | 20 consecutive patients were included, reducing selection bias. | Low | Follow-up panendoscopy and biopsies were used to ensure reliable measurement of HP eradication. | Low | No major confounders were identified; standard treatment regimen used. | Low |
Appendix B. Efficacy of Therapeutic Protocols in Case of Penicillin Allergy *
* For detailed information on individual treatment regimens, including sample sizes and eradication rates, please refer to Table 1. It is important to note that several regimens listed in this appendix are based on a small number of participants (n < 10), which may limit the reliability and generalizability of the reported efficacy outcomes. |
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Study | Year | Country | Study Design | Age (Years) | (n) * | Treatment Details | (n) * of Each Regimen | Success Rate (PP%) | Success Rate (ITT%) |
---|---|---|---|---|---|---|---|---|---|
[14] | 2023 | China | Prospective | 18–70 | 450 | 1st line MI 100 mg b.i.d., M 400 mg q.i.d., B 220 mg b.i.d., E 20 mg b.i.d., 14 days | 150 | 91.7 | 84.0 |
1st line MI 100 mg b.i.d., Cef 500 mg b.i.d., B 220 mg b.i.d., E 20 mg b.i.d., 14 days | 150 | 90.9 | 82.7 | ||||||
1st line Cef 500 mg b.i.d., M 400 mg q.i.d., B 220 mg b.i.d., E 20 mg b.i.d., 14 days | 150 | 88.2 | 82.0 | ||||||
[15] | 2023 | Japan | Retrospective | 38–73 | 53 | 1st line PPI (E 20 mg, L 30 mg, or R 10 mg) b.i.d., C 200 mg b.i.d., M 250 mg b.i.d., 7 days | 8 | 50 | 50 |
1st line V 20 mg b.i.d., C 200 mg b.i.d., M 250 mg b.i.d., 7 days | 35 | 100 | 94.3 | ||||||
1st line: clarithromycin resistance V 20 mg b.i.d., C 200 mg b.i.d., M 250 mg b.i.d., 7 days | 11 | 100 | 90.9 | ||||||
1st line or 2nd line V 20 mg b.i.d., S 50 mg b.i.d., M 250 mg b.i.d., 7 days | 10 | 90 | 90 | ||||||
[16] | 2022 | China | Prospective | 18–65 | 92 | 1st line I 5 mg b.i.d., D 100 mg b.i.d., F 100 mg b.i.d., B 220 mg b.i.d. for 14 days and I 5 mg q.i.d., for an additional 14 days | 92 | 92.9 | 85.9 |
[17] | 2021 | China | Case report | 47 | 1 | 4th line L 500 mg q.d., F 100 mg b.i.d., B 220 mg b.i.d., E 20 mg b.i.d., 14 days | 1 | N/A | N/A |
[18] | 2021 | Japan | Prospective | 49–74 | 17 | 2nd line V 20 mg b.i.d., M 250 mg b.i.d., S 100 mg b.i.d., 7 days | 17 | 88.2 | 88.2 |
[19] | 2021 | Spain | Prospective | mean 56 | 55 | 1st line B, M, T (three tablets q.i.d.; one tablet is an association of the three principles), P 40 mg b.i.d., 10 days | 45 | N/A | 95.6 |
2nd line B, M, T (three tablets q.i.d.; one tablet is an association of the three principles), P 40 mg b.i.d., 10 days | 6 | N/A | 100 | ||||||
3rd line B, M, T (three tablets q.i.d.; one tablet is an association of the three principles), P 40 mg b.i.d., 10 days | 4 | N/A | 50 | ||||||
[12] | 2020 | China | Prospective | 8–13 | 22 | 1st line O 1.0 mg/kg/day q.d. or b.i.d., C 20 mg/kg/day b.i.d., M 20 mg/kg/day b.i.d., or t.i.d., B 6–8 mg/kg/day b.i.d., 14 days | 22 | N/A | 90.9 |
[20] | 2020 | China | Prospective | 21–73 | 112 | 1st line E 20 mg b.i.d., C 500 mg b.i.d., M 400 mg b.i.d., 14 days | 5 | 100 | 100 |
1st line E 20 mg b.i.d., LF 500 mg q.d., M 400 mg b.i.d., 14 days | 1 | 100 | 100 | ||||||
1st and 2nd line E 20 mg b.i.d., T 500 mg q.i.d., M 400 mg b.i.d., 14 days | 2 | 100 | 100 | ||||||
1st and 2nd line E 20 mg b.i.d., B 220 mg b.i.d., C 500 mg b.i.d., M 400 mg q.i.d., 14 days | 22 | 94.1 | 81.8 | ||||||
1st and 2nd line E 20 mg b.i.d., B 220 mg b.i.d, LF 500 mg q.d., M 400 mg q.i.d., 14 days | 10 | 100 | 80 | ||||||
1st and 2nd line E 20 mg b.i.d., B 220 mg b.i.d, T 500 mg q.i.d., M 400 mg q.i.d., 14 days | 72 | 100 | 97.2 | ||||||
[21] | 2020 | Europe | Prospective | 38–68 | 562 | (Drug dose, frequency, and duration not specified) 1st line—PPI, C, M; | 228 | 69 | 69 |
1st line—PPI, C, LF | 50 | 82 | 80 | ||||||
1st line—PPI, B, T, M | 228 | 92 | 91 | ||||||
2nd line—(failed PPI, C, M) PPI, C, LF | 17 | 69 | 71 | ||||||
2nd line—(failed PPI, C, M) PPI, M, LF | 13 | 77 | 77 | ||||||
2nd line—(failed PPI, C, M) PPI, B, T, M | 64 | 82 | 78 | ||||||
2nd line—(failed PPI, C, LF) PPI, B, T, M | 5 | 80 | 80 | ||||||
2nd line—(failed PPI, B, T, M) PPI, C, LF | 3 | 100 | 100 | ||||||
2nd line—(failed PPI, B, T, M) PPI, M, LF | 4 | 75 | 75 | ||||||
3rd line—(failed PPI, C, M and then PPI, C, LF) PPI, B, T, M | 12 | 82 | 75 | ||||||
3rd line—(failed PPI, C, M and then PPI, M, LF) PPI, B, T, M | 5 | 100 | 100 | ||||||
3rd line—(failed PPI, C, M and then PPI, B, T, M) PPI, C, LF | 2 | 50 | 50 | ||||||
3rd line—(failed PPI, C, LF) Repeated PPI, B, T, M | 1 | 0 | 0 | ||||||
3rd line—(failed PPI, B, T, M and PPI, M, LF) PPI, C, M, LF | 1 | 100 | 100 | ||||||
[22] | 2019 | China | Prospective | 18–70 | 118 | 1st line R 10 mg b.i.d., Mi 1000 mg b.i.d., M 400 mg t.i.d., B 220 mg b.i.d., 14 days | 118 | 84.3 | 77.1 |
[23] | 2019 | China | Prospective | 29–57 | 152 | 1st line Cef 500 mg b.i.d., LF 500 mg q.d., E 20 mg b.i.d., B 220 mg b.i.d., 14 days | 152 | 90.1 | 85.5 |
[11] | 2018 | China | Prospective | 25–65 | 66 | 1st line E 20 mg b.i.d., C 500 mg b.i.d., M 400 mg q.i.d., 14 days | 33 | 70 | 63.6 |
1st line E 20 mg b.i.d, C 500 mg b.i.d., M 400 mg q.i.d., B 600 mg b.i.d., 14 days | 33 | 96 | 84.8 | ||||||
[24] | 2017 | Japan | Prospective | 58–79 | 50 | 1st line V 20 mg b.i.d., C 200 or 400 mg b.i.d., M 250 mg b.i.d., 7 days | 20 | 100 | 100 |
1st line PPI (L 30 mg b.i.d. or E 20 mg b.i.d.), C 200 or 400 mg b.i.d., M 750 mg 7 days | 30 | 82.7 | 83.3 | ||||||
[25] | 2017 | Japan | Prospective | 44–72 | 57 | 1st line E 20 mg b.i.d., SF 100 mg b.i.d., M 250 mg b.i.d., 10 days | 33 | 100 | 100 |
2nd line E 20 mg b.i.d., SF 100 mg b.i.d., M 250 mg b.i.d., 10 days | 19 | 84.2 | 84.2 | ||||||
3rd line E 20 mg b.i.d., SF 100 mg b.i.d., M 250 mg b.i.d., 10 days | 5 | 40 | 40 | ||||||
[26] | 2017 | Japan | Retrospective | mean 59 | 88 | 1st line PPI (L 30 mg or R 20 mg) b.i.d., C 200 mg b.i.d., M 250 mg b.i.d., 7 days | 10 | 55.6 | 50 |
2nd line PPI b.i.d., C 200 mg b.i.d., M 250 mg b.i.d., 7 days | 3 | 33.3 | 33.3 | ||||||
1st line V 20 mg b.i.d., C 200 mg b.i.d., M 250 mg b.i.d., 7 days | 13 | 92.3 | 92.3 | ||||||
2nd line V 20 mg b.i.d., C 200 mg b.i.d., M 250 mg b.i.d., 7 days | 1 | 100 | 100 | ||||||
1st line PPI b.i.d., SF 100 mg b.i.d., M 250 mg b.i.d., 7 days | 20 | 100 | 100 | ||||||
2nd line PPI b.i.d., SF 100 mg b.i.d., M 250 mg b.i.d., 7 days | 24 | 100 | 100 | ||||||
1st line V 20 mg b.i.d., SF 100 mg b.i.d., M 250 mg b.i.d., 7 days | 14 | 100 | 100 | ||||||
2nd line V 20 mg b.i.d., SF 100 mg b.i.d., M 250 mg b.i.d., 7 days | 3 | 66.7 | 66.7 | ||||||
[27] | 2017 | Turkey | Prospective | 32–58 | 111 | 1st line R 20 mg b.i.d., B 562 mg b.i.d., M 500 mg t.i.d., T 500 mg q.i.d., 10 days | 111 | 92.5 | 88.3 |
[28] | 2017 | Japan | Retrospective | 26–83 | 5 | 2nd line R 20 mg b.i.d., 250 mg M b.i.d., 100 mg MI b.i.d., 7 days | 5 | N/A | 100 |
[29] | 2016 | China | Prospective | 24–76 | 156 | 3rd line or later line: L 30 mg b.i.d., B 220 mg b.i.d., M 400 mg q.i.d., T 500 mg q.i.d., 14 days | 156 | 95.3 | 87.2 |
[4] | 2015 | Spain | Prospective | mean 52 | 267 | 1st line O 20 mg b.i.d., C 500 mg b.i.d., M 500 mg b.i.d., 7 days | 112 | 59 | 57 |
1st line O 20 mg b.i.d., B 120 mg q.i.d., T (Oxy 500 mg q.i.d. or D 100 mg b.i.d.), M 500 mg t.i.d., 10 days | 50 | 75 | 74 | ||||||
2nd line (after failed OCM) O 20 mg b.i.d., B 120 mg q.i.d., T (Oxy 500 mg q.i.d. or D 100 mg b.i.d.), M 500 mg t.i.d., 10 days | 24 | 38 | 37 | ||||||
2nd line (after failed OCM) O 20 mg b.i.d., C 500 mg b.i.d., LF 500 mg b.i.d., 10 days | 50 | 73 | 64 | ||||||
2nd line (after failed OBTM) O 20 mg b.i.d., C 500 mg b.i.d., LF 500 mg b.i.d., 10 days | 14 | 64 | 64 | ||||||
3rd line O 20 mg b.i.d., C 500 mg b.i.d., LF 500 mg b.i.d., 10 days | 3 | 50 | 33 | ||||||
3rd line O 20 mg b.i.d., C 500 mg b.i.d., RIF 150 mg b.i.d., 10 days | 7 | 20 | 14 | ||||||
3rd line O 20 mg b.i.d., B 120 mg q.i.d., T 500 mg q.i.d., M 500 mg t.i.d., 10 days | 3 | 100 | 100 | ||||||
4th line O 20 mg b.i.d., C 500 mg b.i.d., RIF 150 mg b.i.d., 10 days | 2 | 0 | 50 | ||||||
4th line O 20 mg b.i.d., C 500 mg b.i.d., LF 500 mg b.i.d., 10 days | 2 | 100 | 100 | ||||||
[30] | 2014 | Japan | Retrospective | 46–68 | 28 | 1st line PPI (R 10 mg b.i.d., or L 30 mg b.i.d., or E 20 mg b.i.d.), SF 100 mg b.i.d., M 250 mg b.i.d., 7 days | 7 | 100 | 100 |
1st line PPI (R 10 mg b.i.d., or q.i.d; E 20 mg b.i.d.), SF 100 mg b.i.d., M 250 mg b.i.d., 14 days | 4 | 100 | 100 | ||||||
2nd line PPI (R 10 mg b.i.d., or q.i.d; or E 20 mg b.i.d.), SF 100 mg b.i.d., M 250 mg b.i.d., 7 days | 9 | 100 | 100 | ||||||
2nd line PPI (R 10 mg b.i.d., or q.i.d; or E 20 mg b.i.d.), SF 100 mg b.i.d., M 250 mg b.i.d., 14 days | 3 | 100 | 100 | ||||||
3rd line PPI (R 10 mg b.i.d., or q.i.d; or E 20 mg b.i.d.), SF 100 mg b.i.d., M 250 mg b.i.d., 7 days | 3 | 100 | 100 | ||||||
3rd line PPI (R 10 mg b.i.d., or q.i.d; or E 20 mg b.i.d.), SF 100 mg b.i.d., M 250 mg b.i.d., 14 days | 2 | 100 | 100 | ||||||
[31] | 2012 | Australia | Retrospective | 16–85 | 69 | 2nd line R 20 mg t.i.d., B 240 mg q.i.d., RIF 150 mg b.i.d., CF 500 mg b.i.d., 10 days | 69 | 94.2 | 94.2 |
[32] | 2010 | Spain | Prospective | 33–69 | 50 | 1st line O 20 mg b.i.d., C 500 mg b.i.d., M 500 mg b.i.d., 7 days. | 50 | 55 | 54 |
2nd line O 20 mg b.i.d., C 500 mg b.i.d., LF 500 mg b.i.d., 10 days. | 15 out of the 50 | 73 | 73 | ||||||
[33] | 2006 | Japan | Prospective | 41–63 | 67 | 2nd line R 20 mg b.i.d., MI 100 mg b.i.d., M 250 mg b.i.d., 7 days | 67 | N/A | 85.1 |
[34] | 2006 | Japan | Retrospective | 40–64 | 5 | 1st line PPI (L 30 mg, O 20 mg or R 10 mg q.d.), T 500 mg b.i.d., M 250 mg b.i.d., 7-14 days | 5 | 100 | 80 |
[35] | 2005 | Spain | Prospective | mean 57 | 40 | 1st line O 20 mg b.i.d., C 500 mg b.i.d., M 500 mg b.i.d., 7 days | 12 | 64 | 58 |
2nd line RBC 400 mg b.i.d., T 500 mg q.i.d., M 250 mg q.i.d., 7 days | 17 | 53 | 47 | ||||||
3rd line O 20 mg b.i.d., C 500 mg b.i.d., RIF 150 mg b.i.d., 10 days | 9 | 17 | 11 | ||||||
4th line O 20 mg b.i.d., C 500 mg b.i.d., LF 500 mg b.i.d., 10 days | 2 | 100 | 100 | ||||||
[36] | 2005 | Puerto Rico | Prospective | mean 59 | 20 | 1st line E 40 mg q.i.d., T 500 mg q.i.d., M 500 mg q.i.d., 10 days | 17 | N/A | 84 |
2nd line E 40 mg q.i.d., T 500 mg q.i.d., M 500 mg q.i.d., 10 days | 3 | N/A | 100 |
Study | Year | Country | Study Design | Methods of Diagnosis |
---|---|---|---|---|
[14] | 2023 | China | Prospective | Diagnostic positive in the following:
|
[15] | 2023 | Japan | Retrospective | Diagnostic positive in one of the four tests:
|
[16] | 2022 | China | Prospective | Diagnostic positive in one of the two tests:
|
[17] | 2021 | China | Case report | Diagnostic positive in Histology |
[18] | 2021 | Japan | Prospective | Diagnostic positive in one of the five tests:
|
[19] | 2021 | Spain | Prospective | Diagnostic positive in both:
|
[12] | 2020 | China | Prospective | Diagnostic positive in the following:
|
[20] | 2020 | China | Prospective | Diagnostic positive in one of the two tests:
|
[21] | 2020 | Europe | Prospective | Diagnostic positive in one of the five tests:
|
[22] | 2019 | China | Prospective | Diagnostic positive in one of the two tests:
|
[23] | 2019 | China | Prospective | Diagnostic positive in the three tests:
|
[11] | 2018 | China | Prospective | Diagnostic positive in the following:
|
[24] | 2017 | Japan | Prospective | Diagnostic positive in one of the five tests:
|
[25] | 2017 | Japan | Prospective | Diagnostic positive in one of the two tests:
|
[26] | 2017 | Japan | Retrospective | Diagnostic positive in 13C-UBT |
[27] | 2017 | Turkey | Prospective | Diagnostic positive in Histology |
[28] | 2017 | Japan | Retrospective | Diagnostic positive in the three tests:
|
[29] | 2016 | China | Prospective | Diagnostic positive in the following:
|
[4] | 2015 | Spain | Prospective | Diagnostic positive in the three tests:
|
[30] | 2014 | Japan | Retrospective | Diagnostic positive in the two tests:
|
[31] | 2012 | Australia | Retrospective | Diagnostic positive in one of the two tests:
|
[32] | 2010 | Spain | Prospective | Diagnostic positive in one of the three tests:
|
[33] | 2006 | Japan | Prospective | Diagnostic positive in: Rapid urease test |
[34] | 2006 | Japan | Retrospective | Diagnostic positive in one of the three tests:
|
[35] | 2005 | Spain | Prospective | Diagnostic positive in one of the three tests:
|
[36] | 2005 | Puerto Rico | Prospective | Diagnostic positive in the two tests:
|
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El Boury, K.; Boudarf, H.; Adoud, I.; Ouannass, S.; Abi, O.; Delsa, H.; Lahlou, F.A.; Iskandar, S.; El Jemli, M.; Diawara, I.; et al. Clinical Effectiveness of Penicillin-Free Therapies in First-Line and Rescue Treatments for Helicobacter pylori: A Systematic Review. Antibiotics 2025, 14, 476. https://doi.org/10.3390/antibiotics14050476
El Boury K, Boudarf H, Adoud I, Ouannass S, Abi O, Delsa H, Lahlou FA, Iskandar S, El Jemli M, Diawara I, et al. Clinical Effectiveness of Penicillin-Free Therapies in First-Line and Rescue Treatments for Helicobacter pylori: A Systematic Review. Antibiotics. 2025; 14(5):476. https://doi.org/10.3390/antibiotics14050476
Chicago/Turabian StyleEl Boury, Kenza, Hind Boudarf, Imane Adoud, Soukaina Ouannass, Oussama Abi, Hanane Delsa, Fatima Azzahra Lahlou, Samy Iskandar, Meryem El Jemli, Idrissa Diawara, and et al. 2025. "Clinical Effectiveness of Penicillin-Free Therapies in First-Line and Rescue Treatments for Helicobacter pylori: A Systematic Review" Antibiotics 14, no. 5: 476. https://doi.org/10.3390/antibiotics14050476
APA StyleEl Boury, K., Boudarf, H., Adoud, I., Ouannass, S., Abi, O., Delsa, H., Lahlou, F. A., Iskandar, S., El Jemli, M., Diawara, I., Senhaji, M. A., Balouch, L., Belrhiti, Z., & Kettani Halabi, M. (2025). Clinical Effectiveness of Penicillin-Free Therapies in First-Line and Rescue Treatments for Helicobacter pylori: A Systematic Review. Antibiotics, 14(5), 476. https://doi.org/10.3390/antibiotics14050476