Eradication of Helicobacter pylori: A Clinical Update

Marco Romano, MD; Antonio Cuomo, MD

In This Article

Antimicrobial Resistance

Resistance of H pylori to the limited range of antibiotics that have efficacy in its treatment can severely affect attempts to eradicate the bacteria. Bacterial resistance to antimicrobials can be either primary (ie, present before therapy) or secondary (ie, develop as the result of failed therapy). Resistance to tetracycline or amoxicillin is extremely rare.[31,32] The issue of resistance primarily concerns the nitroimidazoles (metronidazole or tinidazole) and macrolides (clarithromycin).[33,34,35] Prevalence of H pylori resistance to metronidazole is approximately 25%.[36,37] In vitro resistance to metronidazole is not always predictive of results in vivo. Increasing the dosage of metronidazole administered (eg, from 1.0 to 1.5 g/day) generally improves the results of therapy when treating metronidazole-resistant H pylori strains.

Resistance to clarithromycin is becoming more prevalent in some European countries, where the prevalence may be as high as 17%.[36,37] The clinical effect of clarithromycin resistance is essentially complete loss of any clarithromycin anti-H pylori effect; outcome of therapy can generally be predicted on the basis of what could be expected if only the other antimicrobials in the regimen are used.[35]

The increasing prevalence of antimicrobial resistance jeopardizes the success of therapeutic regimens aimed at the eradication of the infection.[38] Currently, most physicians treat H pylori infection without relying on antimicrobial susceptibility testing to select the best regimen. Choosing the treatment regimen on the basis of pretreatment antimicrobial susceptibility testing may significantly decrease the number of treatment failures compared with that obtained with standard triple therapy. In fact, a prospective study conducted at our institution involving 150 H pylori-infected patients showed that an eradication regimen based on the results of pretreatment antimicrobial-susceptibility testing was associated with a higher eradication rate and a significantly lower rate of treatment failure in this population (H pylori-infected dyspeptic subjects; Figure).[39] Comparable results have been obtained by Toracchio and colleagues.[40] Moreover, a cost-benefit analysis taking into account the cost estimates for a number of variables including office visits; performance of endoscopy plus biopsy, rapid urease test, histology, H pylori test culture and antimicrobial susceptibility testing, 13C- urea breath test; and cost-per-tablet of omeprazole, amoxicillin, tetracycline, clarithromycin, metronidazole, and bismuth subcitrate showed that eradication based on the results of antimicrobial susceptibility testing saved up to US $5 per patient. When this was normalized with respect to the effectiveness of the different treatments, H pylori eradication obtained through pretreatment susceptibility testing-based therapy resulted in a cost-effectiveness ratio of approximately US $15 per patient lower when compared with that achieved with standard triple therapy.[39]

 H pylori infection eradication rate in 75 patients treated on the basis of results of susceptibility testing (Testing) and in 75 patients treated with standard triple therapy (No Testing).Key: PP: Per Protocol (75 patients per group); ITT: Intention-to-Treat (73 patients per group)

We postulate that because antimicrobial-resistant strains are becoming increasingly prevalent, therapeutic regimens based on susceptibility testing should always be used as first-line therapy, especially in areas with a high prevalence of resistance to clarithromycin and metronidazole.[41] This approach to treating H pylori infection is more effective and cost-saving and thus may help prevent the emergence of secondary resistance.