A Practical Approach to Patients with Refractory Helicobacter pylori Infection, or Who Are Re-Infected After Standard Therapy

Abstract

The vast majority of recurrences of Helicobacter pylori infection after apparent eradication are observed during the first year. Almost all of these early recurrences are due to recrudescence rather than reinfection by a new strain. After the first year, the recurrence rates approximate to the rate of natural acquisition of H. pylori infection. By contrast, in developing countries, higher rates of recurrence suggest a major role of real reinfection. Important predictive factors of H. pylori treatment success are compliance and bacterial susceptibility to antibiotics. The new 1-week triple therapies, based on a proton pump inhibitor (PPI) and 2 antibiotics, lead to treatment discontinuation but rarely. If containing a nitroimidazole, their efficacy is reduced to 60 to 80% by pretreatment in vitro resistance. The prevalence of nitroimidazole resistance varies dependent on the geographical area, with rates over 50% in tropical regions. Resistance against macrolides hinders treatment success in 50 to 80% of patients. In the US, south-western Europe and Japan the prevalence of macrolide resistance amounts to about 10%, in other countries about 3%. After failed treatment, acquired resistance is frequent. Testing for resistance is recommended to facilitate the decision for an alternative triple therapy or for quadruple therapy comprising bismuth, metronidazole, tetracycline and a PPI. It seems reasonable to increase the dose of PPI in a retreatment regimen containing amoxicillin. Post-treatment double resistance against nitroimidazoles and macrolides reduces the success of most of the currently evaluated retreatment regimens. To overcome double resistance, high dose PPI plus amoxicillin is one approach, beside other experimental multidrug treatments.

“Rescue” regimens after Helicobacter pylori treatment failure

“…Pretreatment antibiotic resistance is the most important factor in nonresponse to initial treatment [25][26][27][28][29] . Thus, the choice of a second-line treatment depends on which treatment was used initially, as it would appear that retreatment with the same regimen cannot be recommended [30] .…”

“…If a clarithromycin-based regimen was used, a metronidazole-based treatment (or at least a clarithromycin-free regimen) should be used afterwards, and vice versa [31] . This recommendation is based on the observation that acquired bacterial resistance to metronidazole or clarithromycin results primarily from the previous treatment failure [26,32,33] , and therefore rescue therapies should avoid these antibiotics and use different combinations.…”

“…Rescue regimen after PPI-clarithromycin-nitroimidazole failure As previously mentioned, acquired bacterial resistance to metronidazole or clarithromycin results primarily from the previous treatment failure [26,32] , and therefore the first choice probably should not be a regimen that combines these two antibiotics in the same regimen [23,24,128] . Although this regimen is very effective [4] , patients who are not cured will probably have double resistance [26,129] , and no logical empirical treatment remains afterwards (although, more recently, the levofloxacin-based regimens may represent an option).…”

“…Although this regimen is very effective [4] , patients who are not cured will probably have double resistance [26,129] , and no logical empirical treatment remains afterwards (although, more recently, the levofloxacin-based regimens may represent an option). Thus, some authors have demonstrated that initial regimens containing both clarithromycin and nitroimidazole are associated with significantly worse results overall, with lower eradication rates after logically chosen second-line therapy and sensitivity-directed third-line therapy; these poor results were due to the emergence of multiple resistant strains as evidenced by the results of culture testing after the second failed course [72] .…”

“…Firstly, omeprazole plus amoxicillin, with a high dose of both the antibiotic and the antisecretor, could, in theory, be recommended [128,130] ; however, we must remember that this "old-fashioned" dual combination has achieved disappointing results in many countries. Therefore, a second antibiotic should be added, and at this point a difficult decision appears, as both antibiotics used in the first trial (clarithromycin and metronidazole) are capable of inducing secondary resistance to H pylori, playing a negative role in future efficacy [25][26][27][28][29]131] . Nevertheless, the following possibilities exist:…”