Background: Helicobacter pylori eradication in penicillin-allergic patients is challenging. The effective regimen is lacking in areas with high antibiotic resistance and tetracycline unavailable. Minocycline, cefuroxime, and full-dose metronidazole are promising drugs. Aims:To compare the eradication rate, safety, and compliance among three new bismuth quadruple therapies for first-line H. pylori eradication in penicillin-allergic patients.Methods: This randomized trial was conducted on 450 naive patients with H. pylori infection and penicillin allergy. The 14-day minocycline-metronidazole-containing (minocycline 100 mg twice daily and metronidazole 400 mg four times/day), minocycline-cefuroxime-containing (minocycline 100 mg twice daily and cefuroxime 500 mg twice daily), and cefuroxime-metronidazole-containing (cefuroxime 500 mg twice daily and metronidazole 400 mg four times/day) bismuth quadruple therapies were randomly assigned to the participants. Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed 4-8 weeks after eradication to evaluate outcome. Results:The differences of eradication rates in either intention-to-treat (84.0%, 82.7%, and 23 82.0%, p = .896) or per-protocol (91.7%, 90.9%, and 88.2%, p = .599) analysis among minocycline-metronidazole, minocycline-cefuroxime, and cefuroximemetronidazole-containing bismuth quadruple therapies were statistically insignificant.The incidence of adverse events (35.1%, 22.6%, and 28.9%) and compliance (90.5%, 91.8%, and 91.9%) were similar. Taste distortion, nausea, and anorexia were more common in metronidazole-containing regimens, and dizziness was more common in minocycline-containing regimens. The allergy was rare (~3%). Conclusions:The efficacies of three bismuth quadruple therapies containing minocycline, cefuroxime, and full-dose metronidazole (pairwise) for first-line H. pylori eradication in penicillin-allergic patients were similarly satisfactory with relatively good safety and compliance. The study was registered in the Chinese Clinical Trials Registration (ChiCTR1900023702). How to cite this article: Zhang Y, Suo B, Tian X, et al. New regimens as first-line eradication therapy for Helicobacter pylori infection in patients allergic to penicillin: A randomized
Background: Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori (H. pylori) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens. Methods: This randomized controlled trial was conducted on 434 nave patients with H. pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 48 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t-test for continuous variables. Results: As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs. 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs. 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs. 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs. 88/214 [41.1%]) and compliance (195/215 [90.7%] vs. 192/214 [89.7%]) were similar between the two groups. Conclusion: The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H. pylori eradication with similar safety and compliance. Trial registration: ClinicalTrials.gov, ChiCTR 1900023646.
Background: Bismuth-based drugs are used to treat Helicobacter pylori infection; however, the antibacterial activity of bismuth, especially against H. pylori, has not been fully elucidated. In this study, the mechanisms by which bismuth exerts its detrimental effects on H. pylori were evaluated. MethodsSix H. pylori strains isolated from different patients were cultured with or without bismuth; proteins and metabolites differentially expressed in these two sets of bacteria were detected via data independent acquisition proteomic and gas chromatographymass spectrometry metabolic approaches, respectively. Gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes database were used to identity pathway enrichment. Results:Bismuth inhibited H. pylori growth in vitro via the following mechanisms: downregulation of virulence proteins CagA and VacA; disruption of flagella assembly responsible for bacterial colonization; and inhibition of antioxidant enzymes, including catalase, catalase-related peroxidase, and superoxide dismutase. Diverse metabolic pathways related to growth and RNA translation in H. pylori were disrupted by bismuth. Bismuth treatment impaired many biological processes in H. pylori, including antioxidant response and purine, pyrimidine, amino acid, and carbon metabolism. ConclusionsThe findings of this study suggest that motility, virulence factors CagA and VacA, antioxidant defense system, and many important metabolic pathways associated with bacterial growth, including nucleotide and amino acid metabolism and translation in H. pylori, are inhibited by bismuth. This study provides novel insights into the mechanism by which bismuth eradicates H. pylori upon being incorporated into quadruple therapy.
Background Empiric therapy for Helicobacter pylori infection results in significantly increased antibiotic resistance and decreased eradication efficacy. The genotypic testing of clarithromycin resistance from stool specimens is a promising method for individualized diagnosis and treatment. This study aimed to determine the status of research and application on this method through a systematic review and meta‐analysis. Methods PubMed, Embase, MEDLINE, and WAN FANG database were searched for relevant literature. The quality of included diagnostic articles was evaluated using the quality Assessment of Diagnostic Accuracy Studies‐2 tool. A bivariate random‐effect model was conducted to calculate the diagnostic accuracy of genotypic testing of clarithromycin resistance. Results A total of 16 diagnostic‐related were included and analyzed after exclusions. The pooled sensitivity and specificity of diagnostic meta‐analysis were 0.93 (95% confidence interval [CI]: 0.90–0.96) and 0.98 (95% CI: 0.93–1.00), respectively. The area under the curve (AUC) of the summary receiver operating characteristic was 0.97 (95% CI: 0.95–0.98). The genotypic testing in stool samples had heterogeneous sensitivity (Q = 37.82, p < .01, I2 = 37.82) and specificity (Q = 60.34, p < .01, I2 = 93.72) in detecting clarithromycin resistance. Purification method, stool sample weight, real‐time PCR, and antimicrobial susceptibility testing as reference accounted for the heterogeneity of pooled sensitivity, while patient age, purification method, stool sample weight, and real‐time PCR for the heterogeneity of pooled specificity. Conclusion The genotypic testing of clarithromycin resistance from stool specimens is an accurate, convenient, noninvasive, and rapid detection technology, providing a definitive diagnosis of clarithromycin resistance and guiding the rational antibiotic selection.
Background Due to general unavailability and common side effects of tetracycline, the clinical application of bismuth quadruple therapy (BQT) is greatly limited. Whether amoxicillin can replace tetracycline in BQT remains unknown. This study aimed to compare the eradication rate, safety and compliance between amoxicillin‐containing and tetracycline‐containing BQT as a first‐line regimen for Helicobacter pylori eradication. Methods This randomized trial was conducted on 404 naïve patients for H. pylori eradication. The participants were randomly assigned to 14‐day amoxicillin‐containing (bismuth potassium citrate 110 mg four times/day, esomeprazole 20 mg twice daily, metronidazole 400 mg four times/day and amoxicillin 500 mg four times/day) and tetracycline‐containing (tetracycline 500 mg four times/day and the other three drugs used as above) BQT. Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed 4–8 weeks after eradication to evaluate outcome. Results As for the eradication rates of amoxicillin‐containing and tetracycline‐containing BQT, the results of both intention‐to‐treat and per‐protocol analyses showed that the difference rate of the lower limit of 95% confidence interval was above −10.0% (intention‐to‐treat analysis: 81.7% vs. 83.2%, with a rate difference of −1.5% [−6.3% to 9.3%]; per‐protocol analysis: 89.0% vs. 91.6%, −2.6% [−4.1% to 9.3%]). The incidence of adverse events in amoxicillin‐containing BQT was significantly lower than tetracycline‐containing BQT (29.5% vs. 39.7%). Both groups achieved relatively good compliance (92.0% vs. 89.9%). Conclusion The eradication efficacy of amoxicillin‐containing BQT was non‐inferior to tetracycline‐containing BQT as a first‐line regimen for H. pylori eradication with better safety and similar compliance.
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