Clarithromycin or levofloxacin in the sequential therapy for H. pylori eradication?

Sirs, We read with great interest the study by Molin-Infante et al.,1 showing that levofloxacin-based triple sequential therapy achieved higher Helicobacter pylori eradication rates than similar clarithromycin-based regimens. We believe that at least five aspects of this trial should be discussed. Firstly, when introducing a novel eradication regimen, the therapeutic option in those patients who failed eradication should be also described. Following clarithromycin-based, standard sequential therapy failure, the infection can be cured in more than 80% by using a 10-day, levofloxacin-based triple re-treatment.2 How were the eradication failure patients following a levofloxacin-based regimen cured? Secondly, the clarithromycin-based sequential therapy used in the present study used metronidazole instead of tinidazole. It is known that metronidazole has a markedly shorter half-life when compared with tinidazole and this could be a cause for concern in H. pylori therapy. Indeed, it has been observed that a metronidazole-based regimen achieved a significantly lower cure rate when compared with the tinidazole-based sequential therapy (301/358 vs. 1919/2075; 84.1% vs. 92.5%; P = 0.001).3 Thirdly, despite the authors’ suggestions, no statistically significant difference emerged in the cure rate between levofloxacin-based and clarithromycin-based sequential regimens by either ITT or PP analysis. In detail, the 95% CI were hugely overlapping between the two treatments, being 75–89% and 69–85% respectively. This would mean that by repeating the study, an eradication rate of 75% and 85% could be observed respectively, thus completely inverting the current result. Therefore, no inference on the difference between the two modified sequential regimens should be performed. Fourthly, a recent study performed in Spain computed a primary levofloxacin resistance as low as 1.8%,4 whereas resistance rates as high as 14.3% have been quoted in Japan, 16.8% in Belgium, 17% in Brazil, 18% in Hong Kong, 19.1% in Italy, 21.5% in Korea and 22.1% in Germany.5 Therefore, it is foreseeable that the eradication rate achieved in the present study with levofloxacin-based regimens is unlikely to be replicated in other countries. Finally, levofloxacin is much more expensive than clarithromycin (in Italy 500 mg levofloxacin = 4.47 euros/tablet; 500 mg clarithromycin = 1.13 euros/tablet). Therefore, cost could be a cause for concern when dealing with a very common disease, such as H. pylori infection. Declaration of personal and funding interests: None.