Levofloxacin- versus metronidazole-based rescue therapy for H. pylori infection in Japan

Abstract

Background.

The ideal second-line treatment regimens for Helicobacter pylori infection may differ between the areas, countries and races.

Aim.

The aim was to confirm which was the better regimen for second-line therapy after treatment failure with a standard triple therapy in Japan, a high dosage of levofloxacin- or metronidazole-based therapy.

Patients.

Sixty outpatients with persistent H. pylori infection after a standard triple therapy were enrolled in this prospective, open-label and randomised trial.

Methods.

The subjects were randomly administered levofloxacin (300 mg b.d.)- or metronidazole (500 mg b.d.)-based therapy with lansoprazole (30 mg b.d.) and amoxicillin (1000 mg b.d.) for 7 days, and the cure rates and side effects were analysed. Antimicrobial susceptibility was also examined before second-line therapy using the E-test.

Results.

Good compliance was obtained without severe side effects in both the groups except for two patients. The cure rates, expressed as intention-to-treat and per-protocol analyses, respectively, were 70.0 and 72.4% in the levofloxacin group, and 96.7 and 100% in the metronidazole group. Each regimen often overcame even clarithromycin-resistant strains.

Conclusion.

Metronidazole-based triple therapy is recommended as second-line therapy in Japan, and levofloxacin-based therapy can be an alternative treatment option.

Introduction

Proton pump inhibitor (PPI)-based triple therapy, containing two antibiotics among amoxicillin (AMOX), clarithromycin (CAM) and metronidazole (MNZ), is widely considered the golden standard for first-line therapy of H. pylori infection [1], [2], [3]. However, the therapeutic efficacy varies widely, ranging 25–95% [4], [5], [6], [7], [8]. Recent years have witnessed a decrease in its cure rate due to the progression of antimicrobial resistance and currently, individuals with refractory H. pylori infection cannot be ignored [9], [10], [11], [12], [13]. Reportedly, poor compliance and antimicrobial resistance, in particular CAM or MNZ resistance, are considered some of the most important factors of treatment failure [9], [11], [14]. It is, therefore, an urgent issue to develop an appropriate eradication strategy.

The best rescue treatment regimens should differ among countries and races because of differences in antimicrobial resistance patterns. In Japan, PPI with AMOX and CAM is recommended by the Japanese Helicobacter Society as first-line therapy against H. pylori infection [15], and the treatment efficacy of this regimen mainly depends on CAM susceptibility [16], [17]. In case of treatment failure, no fixed regimen has been established for second-line therapy in Japan. The ideal rescue regimen should consist of short-term and simple drug combinations using susceptible agents with good compliance and little toxicity. Of several rescue regimens proposed in various countries, the combination of PPI, AMOX and MNZ is often administered as second-line treatment in Japan, where MNZ resistance is relatively uncommon compared to worldwide tendency [18], [19], [20], [21], [22]. The cure rate of the 7-day PPI–AMOX–MNZ regimen as second-line therapy is around 90% in Japan [19], [20], [22]. This regimen has the advantage of compliance because of its simple and short-term treatment. However, MNZ resistance may also be widespread in Japan due to its increased consumption, as with CAM resistance. Furthermore, dual resistance to CAM and MNZ is often detected [21], [23]. Therefore, it is important to find a new effective antibiotic with low toxicity instead of CAM or MNZ.

Of several candidates a new fluoroquinolone, levofloxacin (LVFX), is considered an attractive agent for second-line treatment due to its excellent activity against H. pylori [23], [24]. Our previous study revealed that LVFX has strong activity even against CAM-resistant H. pylori strains in vitro, and the efficacy and safety of LVFX 400 mg-based therapy were confirmed as second-line therapy, showing a successful eradication rate of 70% [24]. According to an Italian trial, LVFX 500 mg-based therapy showed a high re-eradication rate of 94% [25]. Focusing on the difference in LVFX dosage, we hypothesised that a high dosage of LVFX-based therapy could induce increased efficacy, and that this regimen might compare with MNZ-based regimen in efficacy and toxicity in the Japanese population. This study was carried out to confirm which was the ideal second-line regimen for refractory H. pylori infection to a standard triple therapy in Japan, a high dosage of LVFX-based therapy or MNZ-based therapy.