Author(s): Aamir Saleem 1 , Asghar Qasim 2 , Humphrey J O'Connor 3 , Colm A O'Morain [[dagger]] 4
antibiotic resistance; bismuth biskalcitrate; Helicobacter pylori ; single triple capsule
Since the discovery of Helicobacter pylori by Marshall and Warren over two decades ago, there have been ongoing attempts to find an ideal H. pylori eradication therapy. Eradication of H. pylori prevents recurrence of duodenal ulcer [1-8] . A beneficial role of H. pylori eradication in patients with nonulcer dyspepsia has been somewhat controversial [9-11] . The efficacy of standard 7-day triple therapy seems to be decreasing worldwide and the number of nonresponders to first-line therapy in clinical practice may be higher than previously reported  .
A simulation model published by the Cochrane review group has shown that in the long term, H. pylori eradication is cost effective for both gastric and duodenal ulcers  . Several factors have been found to influence the efficacy of standard triple therapy, such as bacterial resistance to antibiotics, compliance, bacterial load in the stomach, CagA status, cigarette smoking and gastro-duodenal pathology  . Among these factors, antibiotic resistance and compliance probably play a greater role in predicting the treatment outcome. Primary clarithromycin resistance can reduce the success rate of 7-day triple therapy to as low as 18-40%  .
In vitro resistance to metronidazole may not accurately reflect in vivo resistance, thereby showing a large variation in cure rates in any single population  . The role of antibiotic susceptibility testing after failure of standard therapy is also controversial  . In a bid to overcome these problems, the recent Maastricht guidelines on H. pylori eradication suggest using bismuth-containing quadruple therapy as an alternative first-line therapy in areas where clarithromycin resistance is more than 20%  . The guidelines also suggest its use as second-line therapy when antibiotic resistance is not a major issue. However, nonavailability of bismuth has been a major hindrance to using this regimen in clinical practice. Use of Pylera ® , a new three-in-one capsule consisting of bismuth subcitrate potassium (40 mg Bi203), metronidazole 125 mg and tetracycline 125 mg, administered as three capsules, four times a day for 10 days with a twice-daily standard dose proton pump inhibitor, showed promising results for H. pylori eradication [19-28] .
Bismuth: historical perspective
Bismuth has played an important role in the history of treatment of peptic ulcer disease. Bismuth was combined with ranitidine and antibiotics for the eradication of H. pylori  . It was also marketed in the form of De-Nol[trademark] (tripotassium dicitrato bismuthate) and has been studied in clinical trials for the management of duodenal and gastric ulcer, nonulcer dyspepsia and H. pylori -induced gastroduodenitis. Healing rates for duodenal ulcer with De-Nol were significantly better than placebo [30,31] and similar to results obtained with cimetidine (Table 1) [32-37] . Duodenal ulcer relapse at 6 and 12 months with De-Nol after initial healing was significantly less than cimetidine  . Short-term treatment with De-Nol compared with placebo has also been shown to be successful in treating nonulcer dyspepsia  . In addition, bismuth has been proven to show an...