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Javier P Gisbert
Department of Gastroenterology
University Hospital “La Princesa”
Triple therapies, which use a combination of a proton pump inhibitor (PPI) and two antibiotics for 7–14 days, are currently the first choice for Helicobacter pylori eradication in most countries.(1,2) However, these regimens still fail to eradicate the organism in a considerable number of patients. Thus, even after more than 20 years of experience in H pylori treatment, the ideal regimen to treat this infection still needs to be found. In the present review, three main issues regarding H pylori treatment – especially related with PPIs – will be investigated using evidence-based methods.
Comparing the efficacy of different PPIs for H pylori eradication
Several studies with lansoprazole plus antibiotics have achieved results similar to those previously reported with omeprazole.(3) Furthermore, several comparative randomised trials have demonstrated that both PPIs are equivalent in the eradication of the infection when prescribed with antibiotics.(4)
Similarly, several studies have demonstrated encouraging results with pantoprazole. From the seven studies included in a recent meta-analysis(5) in which 534 patients received pantoprazole and 603 patients were given other PPIs, the mean H pylori eradication rates were 83% and 81%, respectively, indicating the equivalence of all PPIs.(6,7)
Several studies have evaluated the efficacy of 7–14-day rabeprazole-based regimens.(8) For example, rabeprazole–amoxicillin–clarithromycin for 7–14 days achieved a cure rate of 75–98%;(8) the corresponding figure for rabeprazole–clarithromycin–nitroimidazole was of 85%, a percentage similar to that obtained with other PPIs.(9,10) Furthermore, a meta-analysis of comparative studies(8) demonstrated that rabeprazole was equivalent to other PPIs when prescribed in combination with two antibiotics. (11–13)
Esomeprazole, the (S)-isomer of omeprazole (which consists of a racemic mixture of (S)- and (R)-isomers), is the first PPI to be developed as a single optical isomer. As esomeprazole provides better control of intragastric pH(14,15) and has a higher degree of activity against H pylori than other PPIs,(16) this compound could prove more effective to eradicate H pylori infection when combined with antibiotics. However, the results of a recent meta-analysis(17) showed that esomeprazole and omeprazole efficacies were similar for H pylori eradication when combined with two antibiotics (clarithromycin and either amoxicillin or metronidazole). (18–20)
In summary, all PPIs are of similar efficacy for the eradication of H pylori infection when prescribed with antibiotics.
Prolonging PPI administration for duodenal ulcer healing
Initially, general practice consisted of prescribing omeprazole for a further 2–4 weeks after finalising antibiotic therapy. However, several authors reported very high ulcer healing rates with “short” eradication therapies using PPI for one week only.(18,21–23)
In a recent study,(21) several one-week triple therapies (with PPI) were used, with ulcer healing (at one month) being demonstrated in 90% of the patients with H pylori eradication success. It is interesting to note that, in a second endoscopic control performed one month later (without any additional antisecretory treatment), ulcer healing rate increased to up to 97% in H pylori-negative patients. Thus, it seems that the majority of duodenal ulcers that do not heal initially despite H pylori eradication (in itself an uncommon occurrence) will ultimately heal several weeks later without additional therapy. In summary, just one week of PPI (ie, the usual antibiotic administration period recommended in Europe) is enough to obtain duodenal ulcer healing in most cases.(24) Relevant economic savings and simplicity can be inferred from this conclusion. However, patients with large, refractory or complicated (eg, bleeding) ulcers should continue antisecretory therapy until bacterial eradication has been documented.
The best first-line H pylori eradication therapy
Bismuth-based triple or quadruple therapies are effective to treat H pylori infection. However, the main problem with bismuth-based regimens is its rather complex dosing schedule, and the relatively high incidence of associated adverse effects. Therefore, triple therapies, which use a combination of a PPI and two antibiotics for 7–14 days, are currently considered as first choice for H pylori eradication in most countries.(1,2)
Local prevalence of antimicrobial resistance determines whether it is better to start with a regimen based on clarithromycin or one based on metronidazole. Thus, in areas where the prevalence of metronidazole resistance in the general population is high (which is the case in most countries), triple therapy including a PPI, clarithromycin and amoxicillin may be used if the bacterial sensitivity is unknown.(1)
Furthermore, clarithromycin resistance is currently relatively low (compared with metronidazole) in most populations and, therefore, this clarithromycin-based regimen seems to be a good option.(1)
In addition, some authors have analysed the cost- effectiveness of different strategies (first-line and retreatment) to treat H pylori infection and have demonstrated that, at least in their area, treatment with PPI–clarithromycin–amoxicillin followed by rescue with quadruple therapy if failure is more efficient than the inverse strategy.(25) The dose and scheme of administration of the different drugs are: PPI (at the usual dose), clarithromycin (500mg) and amoxicillin (1g), with all drugs being given twice daily.(2) Nevertheless, regimens based on metronidazole (eg, quadruple therapy) may be used first if the prevalence of clarithromycin resistance is very high.
On the other hand, the first choice should not be a regimen that combines clarithromycin and metronidazole in the same regimen. Although this regimen is highly effective, patients who are not cured will have at least single, and usually double, resistance.(26) Endoscopy with culture and susceptibility testing has been suggested after failure of this regimen.
Therefore, due to problems with resistance, both key antibiotics should probably not be used together until a valid empirical backup regimen becomes available.(26)
European Helicobacter Study Group
Helicobacter pylori Foundation W:www.helico.com
XVII International Workshop of the European Helicobacter Study Group, Vienna, Austria.
22–24 September 2004