Adverse events with bismuth salts for Helicobacter pylori eradication: Systematic review and meta-analysis

Abstract

INTRODUCTIONBismuth salts have been used for centuries in medicine. From a gastroenterology perspective these drugs have been used to treat peptic ulcer disease, dyspepsia, parasitic infections, microscopic colitis, and infectious diarrhoea [1] . The discovery of Helicobacter pylori (H pylori) in 1983 by Warren and Marshall revolutionised the management of peptic ulcer disease [2] , and led to a renewed interest in bismuth compounds, largely because bismuth was found to inhibit the growth of H pylori and was effective in eradicating the organism (when combined with antibiotics or in combination with antibiotics and acid suppression therapy [3,4] ). The first randomised controlled trial (RCT) of bismuth in H pylori-positive individuals suggested that bismuth was superior to erythromycin monotherapy in eradicating the infection [5] . A further RCT of 6 wk of colloidal bismuth subcitrate versus cimetidine, in H pylori-positive duodenal ulcer patients, demonstrated that bismuth successfully eradicated the bacterium in up to 50% of patients [6] . Subsequently, an RCT of both colloidal bismuth subcitrate and cimetidine, alone or in combination with tinidazole, confirmed that colloidal bismuth subcitrate and tinidazole cleared the infection in almost 75% of patients [7] . With the addition of a second antibiotic, tetracycline or amoxicillin, eradication rates in later RCTs exceeded 80% [8][9][10] . However, there were some problems associated with bismuth-based triple therapy, which included the number of tablets patients were required to take, the duration of therapy, and side effects such as altered taste, nausea, and diarrhoea. Abstract AIM: To assess the safety of bismuth used in Helicobacter pylori (H pylori ) eradication therapy regimens. METHODS:We conducted a systematic review and meta-analysis. MEDLINE and EMBASE were searched (up to October 2007) to identify randomised controlled trials comparing bismuth with placebo or no treatment, or bismuth salts in combination with antibiotics as part of eradication therapy with the same dose and duration of antibiotics alone or, in combination, with acid suppression. Total numbers of adverse events were recorded. Data were pooled and expressed as relative risks with 95% confidence intervals (CI). RESULTS: We identified 35 randomised controlled trials containing 4763 patients. There were no serious adverse events occurring with bismuth therapy. There was no statistically significant difference detected in total adverse events with bismuth [relative risk (RR) = 1.01; 95% CI: 0.87-1.16], specific individual adverse events, with the exception of dark stools (RR = 5.06; 95% CI: 1.59-16.12), or adverse events leading to withdrawal of therapy (RR = 0.86; 95% CI: 0.54-1.37).CONCLUSION: Bismuth for the treatment of H pylori is safe and well-tolerated. The only adverse event occurring significantly more commonly was dark stools.

High Efficacy of Levofloxacin-Dexlansoprazole-Based Quadruple Therapy as a First Line Treatment for Helicobacter pylori Eradication in Thailand

“…The previous study demonstrated that adding bismuth might be a good option to improve the eradication by standard triple therapy apart from increasing the dosage and duration of PPI (Srinarong et al, 2014). Several studies also demonstrated that administration of bismuth in quadruple therapy increased the eradication rate of H. pylori up to 90%, comparing to standard triple therapy (Ford et al, 2008;Fock et al, 2009).…”

The challenge of Helicobacter pylori resistance to antibiotics: the comeback of bismuth-based quadruple therapy

“…A systematic review and meta-analysis on all randomized clinical trials comparing bismuth-based treatments with other treatments were conducted by Ford and colleagues [Ford et al 2008]; 35 randomized clinical trials totalling 4763 patients were identified, and 2435 were treated with bismuth salts. No serious adverse event was reported with the bismuth therapy.…”

Comparison of three different regimens against Helicobacter pylori as a first-line treatment: A randomized clinical trial

“…Moreover, with the availability of new single (three in one) capsule-containing bismuth substrate, metronidazole, and tetracycline, the number of tablets needs to be taken in the bismuth quadruple group will be substantially decreased and this will also likely increase drug compliance [28]. The only adverse event that occurred with significant frequency was dark stools [29]. In this study, the most adverse reaction of QT was the dark stool, too.…”