Rifabutin in Patients With 3 H. 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.
MethodsDesign: 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 C-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.
Helicobacter pylori infects approximately 50% of the adult population and is associated with a wide range of upper gastrointestinal diseases including gastritis, peptic ulcer disease and gastric cancer. After almost 30 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has yet to be found. Thus, even with the currently recommended first-line treatment regimens, including a proton pump inhibitor (PPI) plus two antibiotics, ≥20% of patients will fail to eradicate the infection. A 'rescue' therapy with a bismuth-containing quadruple combination has been recommended. However, it still fails to eradicate H. pylori in approximately 20–30% of the patients.
Currently, a standard third-line therapy is lacking, and European guidelines recommend performing culture in these patients to select a third-line treatment according to a microbial sensitivity to antibiotics, but this strategy is currently not practical. Therefore, the evaluation of drugs without cross-resistance to nitroimidazole or macrolides as components of re-treatment combination therapies seems to be worthwhile. Recently, some studies have evaluated the efficacy of new fluoroquinolones, such as levofloxacin, which could prove to be a valid alternative to standard antibiotics. In few cases, however, H. pylori infection persists even after three eradication treatments and these patients constitute a therapeutic dilemma.
Rifabutin is a rifamycin-S derivative, which is commonly used to treat Mycobacterium avium-intracellulare complex in human immunodeficiency virus (HIV)-infected patients. This antibiotic has potential utility against H. pylori because the in vitro sensitivity is high. The in vitro MIC of rifabutin against H. pylori was 0.004–0.008 μg/mL, a value that was four, six and 50 times lower than that found for amoxicillin, clarithromycin and metronidazole respectively. Furthermore, rifabutin does not share resistance to clarithromycin, and the selection of resistant H. pylori strains has been low in experimental conditions. Consequently, rifabutin-based rescue therapies represent a potential strategy for eradication failures. However, the experience with this drug in H. pylori treatment is still very limited.
Therefore, the aim of the present study was to evaluate the efficacy of an empirical fourth-line rescue regimen with rifabutin in patients with three eradication failures.
Abstract and Introduction
Abstract
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.
MethodsDesign: 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 C-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.
Introduction
Helicobacter pylori infects approximately 50% of the adult population and is associated with a wide range of upper gastrointestinal diseases including gastritis, peptic ulcer disease and gastric cancer. After almost 30 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has yet to be found. Thus, even with the currently recommended first-line treatment regimens, including a proton pump inhibitor (PPI) plus two antibiotics, ≥20% of patients will fail to eradicate the infection. A 'rescue' therapy with a bismuth-containing quadruple combination has been recommended. However, it still fails to eradicate H. pylori in approximately 20–30% of the patients.
Currently, a standard third-line therapy is lacking, and European guidelines recommend performing culture in these patients to select a third-line treatment according to a microbial sensitivity to antibiotics, but this strategy is currently not practical. Therefore, the evaluation of drugs without cross-resistance to nitroimidazole or macrolides as components of re-treatment combination therapies seems to be worthwhile. Recently, some studies have evaluated the efficacy of new fluoroquinolones, such as levofloxacin, which could prove to be a valid alternative to standard antibiotics. In few cases, however, H. pylori infection persists even after three eradication treatments and these patients constitute a therapeutic dilemma.
Rifabutin is a rifamycin-S derivative, which is commonly used to treat Mycobacterium avium-intracellulare complex in human immunodeficiency virus (HIV)-infected patients. This antibiotic has potential utility against H. pylori because the in vitro sensitivity is high. The in vitro MIC of rifabutin against H. pylori was 0.004–0.008 μg/mL, a value that was four, six and 50 times lower than that found for amoxicillin, clarithromycin and metronidazole respectively. Furthermore, rifabutin does not share resistance to clarithromycin, and the selection of resistant H. pylori strains has been low in experimental conditions. Consequently, rifabutin-based rescue therapies represent a potential strategy for eradication failures. However, the experience with this drug in H. pylori treatment is still very limited.
Therefore, the aim of the present study was to evaluate the efficacy of an empirical fourth-line rescue regimen with rifabutin in patients with three eradication failures.
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