Fourth-line rescue therapy with rifabutin in patients with three Helicobacter pylori eradication failures

Background In some cases, Helicobacter pylori infection persists even after three eradication treatments. Aim To evaluate the efficacy of an empirical fourth-line rescue regimen with rifabutin in patients with three eradication failures. Methods Design: Multicentre, prospective study. Patients: In whom the following three treatments had consecutively failed: first (PPI + clarithromycin + amoxicillin); second (PPI + bismuth + tetracycline + metronidazole); third (PPI + amoxicillin + levofloxacin). Intervention: A fourth regimen with rifabutin (150 mg b. d.), amoxicillin (1 g b. d.) and a PPI (standard dose b. d.) was prescribed for 10 days. Outcome: Eradication was confirmed by 13C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated using a questionnaire. Results One-hundred patients (mean age 50 years, 39% men, 31% peptic ulcer/69% functional dyspepsia) were included. Eight patients did not take the medication correctly (in six cases due to adverse effects). Per-protocol and intention-to-treat eradication rates were 52% (95% CI = 41-63%) and 50% (40-60%). Adverse effects were reported in 30 (30%) patients: nausea/vomiting (13 patients), asthenia/ anorexia (8), abdominal pain (7), diarrhoea (5), fever (4), metallic taste (4), myalgia (4), hypertransaminasemia (2), leucopenia (< 1,500 neutrophils) (2), thrombopenia (< 150 000 platelets) (2), headache (1) and aphthous stomatitis (1). Myelotoxicity resolved spontaneously in all cases. Conclusions Even after three previous H. pylori eradication failures, an empirical fourth-line rescue treatment with rifabutin may be effective in approximately 50% of the cases. Therefore, rifabutin-based rescue therapy constitutes a valid strategy after multiple previous eradication failures with key antibiotics, such as clarithromycin, metronidazole, tetracycline and levofloxacin.