How to Effectively Use Bismuth Quadruple Therapy

Abstract

Bismuth triple therapy was the first truly effective Helicobacter pylori eradication therapy. The addition of a proton pump inhibitor largely overcame the problem of metronidazole resistance. Resistance to its being the primary first line therapy have centered on convenience (the large number of tablets required) and side effects causing difficulties with patient adherence. Understanding why the regimen is less successful in some regions remains unexplained in part because of the lack of studies including susceptibility testing. A number of modifications have been proposed such as twice-a-day therapy which addresses both major criticism but the studies with susceptibility testing required to prove its effectiveness in high metronidazole resistance areas are lacking. Most publications lack the data required to understand why they were successful or failed (e.g., detailed resistance and adherence data) and are therefore of little value. We discuss and provide recommendations regarding variations including substitution of doxycycline, amoxicillin, and twice a day therapy. We describe what is known and unknown and provide suggestions regarding what is needed to rationally and effectively use bismuth quadruple therapy. Its primary use is when penicillin cannot be used or when clarithromycin and metronidazole resistance is common. Durations of therapy less than 14 days are not recommended.

Role of bismuth in improvingHelicobacter pylorieradication with triple therapy

“…In Iran and Turkey, antimicrobial resistance in general is common and both countries typically report low cure rates irrespective of the therapy offered (eg, various triple therapies, bismuth quadruple and the non-bismuth quadruple therapies) 1 3 44. High rates of antimicrobial resistance and even multidrug resistance have also been reported from both areas 13. We recently reviewed the published studies using bismuth quadruple therapy from Turkey and Iran and confirmed that the results were variable 13.…”

“…High rates of antimicrobial resistance and even multidrug resistance have also been reported from both areas 13. We recently reviewed the published studies using bismuth quadruple therapy from Turkey and Iran and confirmed that the results were variable 13. It is unclear why, however, in developing countries it is more common to find drugs with reduced activity, outdated and even counterfeit,45 thus adding an additional unquantifiable variable.…”

“…With low-dose metronidazole, 500 mg two times per day, resistance is effectively all-or-none thus producing results similar to that obtained with clarithromycin resistance. However, the cure rate in the presence of resistance without bismuth can increase to >60% when the dose is 1500 mg or greater 13 16 18. The good success in China probably reflects the higher dose of metronidazole used 9…”

“…The very low cure rates reported in some trials suggest an even more complex situation such as the presence of amoxicillin resistance,56 poor cure rates with resistant infections, poor patient adherence and possibly one or more drugs with poor bioavailability. For example, in Turkey, the addition of bismuth failed to improve the results with PPI, metronidazole and tetracycline therapy,13 57 suggesting poor bioavailability of at least one component. Study interpretation requires susceptibility data.…”

Noninvasive molecular analysis ofHelicobacter pylori: Is it time for tailored first-line therapy?

“…However, in Asia even tetracycline resistance rates of 19% are reported[16]. Therefore, an interesting question for the future could be represented by the risk of an increase of resistance to this antibiotic due to its use on a large scale and the incomplete patient adherence to its intake[17].…”