Helicobacter ISSN 1523-5378 © 2007 The Authors 50 Journal compilation © 2007 Blackwell Publishing Ltd, Helicobacter 12 (Suppl. 2): 50–58 Blackwell Publishing Ltd Oxford, UK HEL Helicobacter 1083-4389 Blackwell Publishing Ltd, 2007 XXX Original Articles Meta-analysis of H. pylori Therapies Gisbert et al. Evolution of Helicobacter pylori Therapy from a Meta-analytical Perspective Javier P. Gisbert, * Ramón Pajares † and José María Pajares * * Gastroenterology Unit, Hospital Universitario de la Princesa, Universidad Autónoma; † Gastroenterology Unit, Hospital Universitario de la Paz, Universidad Autónoma, Madrid, Spain Abstract Even before the discovery of Helicobacter pylori as their cause, chronic gastritis and peptic ulcer disease were empirically treated with anti-infectious agents. However, it was not until that finding that an antibiotic approach began to be used systematically. The main aim of this article is to review the evolution of H. pylori therapy from a meta-analytical perspective. Initially, antibiotic monotherapy had a minor efficacy on H. pylori. Dual therapy including either bismuth compounds or proton-pump inhibitors (PPI) and one antibiotic also resulted in insufficient cure rates. Bismuth-based triple therapy (the first used) and PPI-based triple therapies (combined with two antibiotics, including amoxicillin, nitroimidazole, or clarithromycin) have been the most widely recommended. PPI-based regimens are superior to H 2 -antagonist–based ones. The influence of the type of PPI, the dose and the duration of the treatment will be discussed. Among the factors influencing the efficacy of therapy, resistance to clarithromycin and metronidazole are the most important risk factors for eradication failure. Several rescue therapies can be used. Bismuth-based quadruple therapy is effective, but the complexity of the regimen and the associated adverse effects limit the compliance. PPI-based triple therapy with amoxicillin and levofloxacin is at least equally effective and better tolerated. Keywords proton pump inhibitor, bismuth, ranitidine bismuth citrate, clarithromycin, amoxicillin, levofloxacin, rescue, treatment. Reprint requests to: José Maria Pajares, MD, Gastroenterology Unit. Hospital Universitario de la Princesa., Diego de León, 62. 28006 Madrid. Spain. E-mail: jmpajaresg@telefonica.net Conflicts of interest: the authors have declared no conflicts of interest. Empiric anti-infectious therapies to treat gastritis and peptic ulcer (PU) have been reported for many years before Campylobacter pylori (Helicobacter pylori) was discovered. In 1936, the Russian Large Medical Encyclopedia described infection as one of the causes of PU. In this respect, some articles published successful healing of PU in patients treated with penicillin-streptomycin and metronidazole [1]. In 1949, in Spain, Solano published successful healing of PU in patients treated with their own serum and penicillin [2]. In 1957, Lykoudis, a Greek general practitioner, suffered from PU complicated by recurrent gastrointestinal bleeding. He treated himself for an infectious gastroenteritis with antibiotics (oxyquinoleine, streptomycin, and phthaly- lsulfathiazole), curing his gastroenteritis and obtaining a sustained remission of his PU symptoms. He repeated his own antibiotic treatment in his PU patients, curing the PU in several of them [3]. In 1972, in China, a double- blind randomized, and placebo-controlled clinical trial, using a 2-week regimen of furazolidone demonstrated an ulcer healing rate of 73% versus 24% in the placebo group [4]. Once Campylobacter-like organisms (CLO) were discovered as the cause of PU by Warren and Marshall, the first treatment was offered by Marshall in October 1981 to an elderly Russian man diagnosed with gastritis by endoscopy and with gastric biopsies showing a large number of Gram-negative CLO. The patient accepted a 14-day course with oral tetracycline. The antibiotic therapy relieved the gastric pain and other symptoms. A second endoscopy showed some improvement of the endoscopic gastritis signs, the gastric histology was near normal, and CLOs were not found [5]. The same author reported the healing of PU lesions, confirmed endoscopi- cally, in a patient treated with the bismuth salt DeNol ® (colloidal bismuth subcitrate) (Gist Brocades, The Nether- lands) as well as metronidazole to treat a mouth infection. Therefore, Marshall suggested the synergistic effect of metronidazole and the bismuth compound and treated 10 PU patients infected by metronidazole-susceptible strains of CLO with metronidazole plus DeNol ® , achieving an eradication in 8 of the 10 patients [5]. In 1986, Goodwin et al. treated one patient with bismuth salts plus amoxicillin, curing both the C. pylori infection