Two-week, high-dose proton pump inhibitor, moxifloxacin triple Helicobacter pylori therapy after failure of standard triple or non-bismuth quadruple treatments

Abstract

Background

Aim was to evaluate the efficacy and tolerability of a moxifloxacin-containing second-line triple regimen in patients whose previous Helicobacter pylori eradication treatment failed.

Methods

Prospective multicentre study including patients in whom a triple therapy or a non-bismuth-quadruple-therapy failed. Moxifloxacin (400 mg qd), amoxicillin (1 g bid), and esomeprazole (40 mg bid) were prescribed for 14 days. Eradication was confirmed by ¹³C-urea-breath-test. Compliance was determined through questioning and recovery of empty medication envelopes.

Results

250 patients were consecutively included (mean age 48 ± 15 years, 11% with ulcer). Previous (failed) therapy included: standard triple (n = 179), sequential (n = 27), and concomitant (n = 44); 97% of patients took all medications, 4 were lost to follow-up. Intention-to-treat and per-protocol eradication rates were 82.4% (95% CI, 77–87%) and 85.7% (95% CI, 81–90%). Cure rates were similar independently of diagnosis (ulcer, 77%; dyspepsia, 82%) and previous treatment (standard triple, 83%; sequential, 89%; concomitant, 77%). At multivariate analysis, only age was associated with eradication (OR = 0.957; 95% CI, 0.933–0.981). Adverse events were reported in 25.2% of patients: diarrhoea (9.6%), abdominal pain (9.6%), and nausea (9.2%).

Conclusion

14-day moxifloxacin-containing triple therapy is an effective and safe second-line strategy in patients whose previous standard triple therapy or non-bismuth quadruple (sequential or concomitant) therapy has failed, providing a simple alternative to bismuth quadruple regimen.

Introduction

Helicobacter pylori infection is the main known cause of gastritis, gastroduodenal ulcer disease, and gastric cancer [1]. However, despite more than 30 years of experience in H. pylori treatment, the ideal regimen to treat this infection remains undefined. Consensus conferences have recommended therapeutic regimens that achieve cure rates higher than 80% on an intention-to-treat basis [2]. However, large clinical trials and meta-analyses have shown that the most commonly used first-line therapies – a proton pump inhibitor (PPI) plus 2 antibiotics – can fail in ≥20% of patients, and, in clinical practice, this rate might be even higher [1], [3]. Moreover, during the last few years, the efficacy of standard triple regimens has been decreasing, and several studies have reported intention-to-treat eradication rates lower than 75% and even lower than 50% [4]. Antibiotic resistance to clarithromycin has been identified as one of the major factors affecting our ability to cure H. pylori infection, and the rate of resistance to this antibiotic seems to be increasing in many geographic areas [5].

A rescue regimen comprising a quadruple combination of a PPI, bismuth, tetracycline, and metronidazole has been used as the optimal second-line approach based on the relatively good results reported [6], [7]. However, administration of the regimen is complex and adverse events are relatively common [6], [7]. Furthermore, the quadruple regimen still fails to eradicate H. pylori in approximately 20–30% of cases. Finally, bismuth salts are no longer available worldwide. Therefore, management of first-line eradication failures is becoming challenging.

Non-bismuth quadruple “sequential” and “concomitant” regimens, including a PPI, amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as first-line treatments for H. pylori infection [8], [9]. However, eradication with rescue regimens may be challenging after failure of key antibiotics such as clarithromycin and nitroimidazoles.

Recent findings indicate that fluoroquinolones such as levofloxacin could prove to be an efficacious alternative to standard antibiotics, not only as first-line therapies but also, and more interestingly, as second-line regimens [10], [11], [12]. We previously obtained “intermediate” results (74% eradication rate) with a combination of a PPI, amoxicillin, and levofloxacin given for 10 days in multicenter studies performed in Spain [13], [14]. On the other hand, recent studies suggest that the efficacy of levofloxacin-containing therapy is decreasing, most likely due to increased primary quinolone resistance [15].

Moxifloxacin is a second-generation fluoroquinolone with a wide antibacterial spectrum [16]. Studies in vitro have shown that moxifloxacin has an improved coverage of Gram-positive and anaerobic bacteria while retaining good activity against Gram-negative bacteria [16]. Moxifloxacin has a higher in vitro activity against gram-positive and anaerobic pathogens compared with levofloxacin [17]. In vitro studies have shown excellent susceptibility of H. pylori strains to moxifloxacin [18], and clinical trials have confirmed its higher effectiveness – as a first-line therapy – compared with standard clarithromycin-based triple therapy [19]. Furthermore, few studies have suggested that the emergence of bacterial resistance appears to be less common for moxifloxacin than for other fluoroquinolones, and that moxifloxacin may be less affected by quinolone resistance than levofloxacin in H. pylori [18] and other bacterial infections [20], [21].

Therefore, the aim of the present study was to evaluate the efficacy and tolerability of a second-line triple regimen containing moxifloxacin in patients whose previous H. pylori eradication treatment failed.