Effective Helicobacter pylori (H. pylori) eradication is a major public health concern; however, eradication failure rates with the standard triple therapy remain high. We aimed to investigate the effectiveness and tolerability of ranitidine bismuth citrate (RBC) pretreatment before standard triple therapy for H. pylori eradication. A prospective, randomized, controlled, and open-label clinical trial was conducted from June to December 2019. H. pylori eradication rate, safety, and tolerability were compared between the standard treatment group (esomeprazole, amoxicillin, and clarithromycin for 7 days) and RBC pretreatment group (RBC for 2 weeks before standard triple therapy). This trial ended earlier than estimated owing to the N-nitrosodimethylamine concerns with ranitidine. Success rates of H. pylori eradication were 80.9% and 67.3% in the RBC pretreatment (n = 47) and standard treatment (n = 52) (p = 0.126) groups, respectively. Our trial was discontinued earlier than planned; however, a statistical significance would be achieved by expansion of our data (p = 0.031) if patient enrollment numbers reached those initially planned. Adverse event rates were comparable between groups (25.5% in the pretreatment group vs. 28.8% in the standard treatment group), without serious event. Tolerability was excellent in both groups, recorded as 97.9% and 100% in the pretreatment and standard treatment groups, respectively. Compared with the standard triple regimen, RBC pretreatment for 2 weeks may achieve higher H. pylori eradication rates, with excellent safety and tolerability. However, this study necessitates further validation as it was discontinued early owing to the N-nitrosodimethylamine issues of ranitidine.

Background: Administration of aspirin has the potential for significant side effects of gastrointestinal (GI) injury mainly caused by gastric acid stimulation, especially in long-term users or users with original gastrointestinal diseases. The debate on the optimal treatment of aspirin-induced gastrointestinal injury is ongoing. We aimed to compare and rank the different treatments for aspirin-induced gastrointestinal injury based on current evidence. Methods: We searched PubMed, EMBASE, Cochrane Library (Cochrane Central Register of Controlled Trials), and Chinese databases for published randomized controlled trials (RCTs) of different treatments for aspirin-induced gastrointestinal injury from inception to 1 May 2021. All of the direct and indirect evidence included was rated by network meta-analysis under a Bayesian framework. Results: A total of 10 RCTs, which comprised 503 participants, were included in the analysis. The overall quality of evidence was rated as moderate to high. Eleven different treatments, including omeprazole, lansoprazole, rabeprazole, famotidine, geranylgeranylacetone, misoprostol, ranitidine bismuth citrate, chili, phosphatidylcholine complex, omeprazole plus rebamipide, and placebo, were evaluated in terms of preventing gastrointestinal injury. It was suggested that omeprazole plus rebamipide outperformed other treatments, whereas geranylgeranylacetone and placebo were among the least treatments. Conclusion: This is the first systematic review and network meta-analysis of different treatments for aspirin-induced gastrointestinal injury. Our study suggested that omeprazole plus rebamipide might be considered the best option to treat aspirin-induced gastrointestinal injury. More multicenter, high quality, large sample size randomized controlled trials will confirm the advantages of these medicines in the treatment of aspirin-induced gastrointestinal injury in the future.

SARS-CoV-2 is causing a pandemic of COVID-19, with high infectivity and significant mortality1. Currently, therapeutic options for COVID-19 are limited. Historically, metal compounds have found use as antimicrobial agents, but their antiviral activities have rarely been explored. Here, we test a set of metallodrugs and related compounds, and identify ranitidine bismuth citrate, a commonly used drug for the treatment of Helicobacter pylori infection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo. Ranitidine bismuth citrate exhibited low cytotoxicity and protected SARS-CoV-2-infected cells with a high selectivity index of 975. Importantly, ranitidine bismuth citrate suppressed SARS-CoV-2 replication, leading to decreased viral loads in both upper and lower respiratory tracts, and relieved virus-associated pneumonia in a golden Syrian hamster model. In vitro studies showed that ranitidine bismuth citrate and its related compounds exhibited inhibition towards both the ATPase (IC50 = 0.69 µM) and DNA-unwinding (IC50 = 0.70 µM) activities of the SARS-CoV-2 helicase via an irreversible displacement of zinc(II) ions from the enzyme by bismuth(III) ions. Our findings highlight viral helicase as a druggable target and the clinical potential of bismuth(III) drugs or other metallodrugs for the treatment of SARS-CoV-2 infection.

Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent disease with a prolonged clinical course that most often involves the stomach. Clinically, for Helicobacter pylori-positive low-grade MALT lymphoma, antibiotics have been used as the first-line treatment. The recommended anti-Helicobacter triple drug therapy includes a proton pump inhibitor (or ranitidine bismuth citrate), clarithromycin, and amoxicillin (or metronidazole). Considering the difficulty involved with confirming histological remission and the lack of systemic endoscopic follow-up, much work remains to be done in this area. This review describes MALT lymphoma treatment methods and their efficacy, highlights results of the newest studies, and proposes avenues toward future developments in this field.

Helicobacter pylori is reported as the etiological agent of gastritis, gastric and duodenal ulcer, gastric adenoid carcinoma and mucosa-associated lymphoid tissue lymphoma. In the diagnosis of H.pylori infections invasive (culture, histopathological examination, rapid urease test and molecular tests) and non-invasive (urea breath test, serological tests, stool culture and stool antigen/nucleic acid tests) methods may be used. Clarithromycin, amoxicillin and combination of metronidazole and protonpump inhibitor or ranitidine bismuth citrate triple treatment protocol is applied in order to treat and eradicate the infection. However, increasing rates of antibiotic resistance among H.pylori strains reduces the success of eradication therapy. The aim of this study was to investigate the presence of H.pylori in the gastric antral biopsy specimens and to determine the antimicrobial resistance of the isolates. A total of 149 gastric antral biopsy specimens obtained from patients (age range: 17-83 years; 73 were male) who admitted to Mersin University Faculty of Medicine Department of Internal Medicine Gastroenterology clinic with dyspeptic complaints were included in the study. H.pylori presence was investigated by culture, polymerase chain reaction (PCR) and urease test from gastric biopsy specimens, and H.pylori-specific antigen (HpSA) was investigated by ELISA in the stool samples of patients. Resistance to tetracycline, amoxicillin, metronidazole and levofloxacin was determined with E-test method. Clarithromycin resistance was determined both by E-test and PCR-RFLP (restriction fragment length polymorphism) methods. H.pylori was detected in 29.6% (43/145) of patients with culture, 55.2% (80/145) of patients with urease test, 57% (65/114) of patients with HpSA test and 71.3% (102/143) of patients with PCR. The sensitivity and specificity of culture, PCR, HpSA and urease tests were determined as 52.4% and 100%, 96.3% and 62.3%, 80.3% and 81.4%, 86.6% and 85.7%, respectively. According to the E-test results, resistance to clarithromycin was 18.2%, to tetracycline 9.1%, to metronidazole 45.5%, to levofloxacin 18.2% and no resistance was determined to amoxicillin. Clarithromycin resistance was searched in 94 of PCR positive 102 samples, and 17 (18.1%) of them yielded clarithromycin resistance. Of them 11 (64.7%) harbored A2144G (at 2144. nucleotide), and 6 (%35.3) harbored A2143G (at 2143. nucleotide) point mutations. In our study, PCR was determined as the most sensitive method, however due to its low specificity, the results should be confirmed with at least one of the other methods. The specificity of culture method was high, but sensitivity was found to be quite low compared with other methods. The sensitivity and specificity of urease and HpSA tests were found to be similar. In conclusion, in cases which endoscopy could not be done, non-invasive, rapid and practical HpSA method can be used in diagnosis and monitorization of the treatment. In the case of treatment failure, culture should be performed for antibiotic susceptibility testing of the isolate.

The aim of the present investigation was to prepare and evaluate a vesicular dual-drug delivery system for effective management of the mucosal ulcer. Inner encapsulating and double liposomes were prepared by the glass-bead and reverse-phase evaporation methods, respectively. The formulation consisted of inner liposomes bearing ranitidine bismuth citrate (RBC) and outer liposomes encapsulating amoxicillin trihydrate (AMOX). The optimized inner liposomes and double liposomes were extensively characterized for vesicle size, morphology, zeta potential, vesicles count, entrapment efficiency, and in vitro drug release. In vitro, the double liposomes demonstrated a sustained release of AMOX and RBC of 93.6 ± 1.9 and 84.1 ± 0.9%, respectively, at the end of 144 hours. Ex vivo studies were conducted on Helicobacter pylori (ATCC26695) bacterial cell lines. Double liposomes showed a more enhanced percent H. pylori growth inhibition than the plain drug combination. Further, in vivo studies illustrated enhanced antisecretory and ulcer-protective activity of double liposomes, as compared to the plain drug combination. Microscopic studies also supported the ulcer-protective action of the formulation. Thus, it may be concluded that double liposomes are instrumental in reducing gastric secretions and targeting ulcer sites with the interception of minimal side effects, thus suggesting their potential in ulcer therapy.

In the present study the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Studies concerning the eradication of Helicobacter pylori have resulted in a proliferation of meta-analyses. To date, there are 303 meta-analyses cited in PubMed, 113 dealing with the therapy of the infection. A chronological analysis of the results of meta-analyses performed between 1998 and 2010 shows that first-line standard triple therapies achieved eradication rates on an intention-to-treat basis of around 80%; prolonging treatment to 14, but not 10 d should improve the results. The proton pump inhibitors have a similar efficiency, and giving a double dose is more efficient than the standard doses of these drugs. Triple and quadruple therapies proved to be equivalent. Based on meta-analytical data, the decrease in efficiency over time cannot be substantiated: eradication rates < 80% followed from the introduction of triple therapies. As alternatives, ranitidine bismuth citrate-, levofloxacin- or furazolidone-based therapies were shown to obtain the same eradication rates as standard triple regimens. Sequential therapies and quadruple non-bismuth-based therapies were superior to standard triple therapies but their use is limited to certain countries. In the author's opinion, and from a meta-analytical viewpoint, standard triple therapies cannot yet be considered obsolete. Furthermore, non-inferiority trials are proposed for the future, including assessment of local contemporary antimicrobial resistance profiles and the CagA and CYP2C19 status of the enrolled patients.

Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. H. pylori eradication has been shown to have a prophylactic effect against gastric cancer. According to several international guidelines, the first-line therapy for treating H. pylori infection consists of a proton pump inhibitor (PPI) or ranitidine bismuth citrate, with any two antibiotics among amoxicillin, clarithromycin and metronidazole, given for 7-14 days. However, even with these recommended regimens, H. pylori eradication failure is still seen in more than 20% of patients. The failure rate for first-line therapy may be higher in actual clinical practice, owing to the indiscriminate use of antibiotics. The recommended second-line therapy is a quadruple regimen composed of tetracycline, metronidazole, a bismuth salt and a PPI. The combination of PPI-amoxicillin-levofloxacin is a good option as second-line therapy. In the case of failure of second-line therapy, the patients should be evaluated using a case-by-case approach. European guidelines recommend culture before the selection of a third-line treatment based on the microbial antibiotic sensitivity. H. pylori isolates after two eradication failures are often resistant to both metronidazole and clarithromycin. The alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be promising.