Sequential Therapy for Helicobacter Pylori Eradication: The Time is Now!

Abstract

Helicobacter pylori treatment still remains a challenge for physicians, and no current first-line therapies are able to cure the infection in all treated patients. Two very large meta-analysis studies showed that standard 7—14 days triple therapies fail to eradicate H. pylori infection in up to 20—25% of patients [Fuccio et al. 2007; Zullo et al. 2007]. In addition, the efficacy of these regimens is even decreasing worldwide. Indeed, during the last few years, different studies have found that the success rate following such regimens is disappointingly low, with values less than 45—60% in some countries [Gumurdulu et al. 2004; Vakil et al. 2004]. This phenomenon most likely depends on an increased bacterial resistance to antibiotics, particularly against clari-thromycin — the key antibiotic in H. pylori treatment [Megraud 2004]. In detail, clarithromycin resistance reduces success rate of standard triple therapies to mean values as low as 18—44%. Consequently, several patients deserve two or more therapeutic attempts to cure H. pylori infection in clinical practice. Therefore, as well as first-line regimens, both second-line and ‘rescue’ therapies have been advised in the updated international guidelines for H. pylori management [Caselli et al. 2007; Malfertheiner et al. 2007]. However, to cure the infection following a failed initial triple therapy is particularly difficult and costly, due to the need for further therapies and diagnostic tests. In a recent study, the cumulative eradication rate was 89.6% by using three consecutive standard therapies in patients treated in clinical practice, being only 70.3%, 69.1% and 70% following first-, second-, and third-line regimens, respectively [Rokkas et al. 2009]. All these observations clearly suggest that more efficacious therapy regimens are required as an initial therapy for clinical practice, the best first-line treatment being still regarded as the best ‘rescue’ therapy [Huang and Hunt 1999]. In 2000, we conceived a novel therapeutic approach to cure H. pylori infection, namely a 10-day sequential therapy, which achieved a very high eradication rate [Zullo et al. 2000]. The sequential therapy is a simple dual therapy including a proton pump inhibitor (PPI) plus amoxicillin 1 g (both twice daily) given for the first 5 days followed by a triple therapy including a PPI, clarithromycin 500 mg, and tinidazole (all twice daily) for the remaining 5 days [Zullo et al. 2007]. To date, the efficacy of such a therapy regimen has been investigated in several trials overall enrolling more than 2000 patients. Based on these results, sequential therapy is now recognized as first-line therapy in the current Italian guidelines [Caselli et al. 2007].