RESUMO
AIM: To investigate a 1-week once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for rescue therapy of Helicobacter pylori infection. METHODS: Consecutive patients (n = 103) with at least one previous treatment failure and H. pylori infection resistant to both metronidazole and clarithromycin were treated with esomeprazole 40 mg, moxifloxacin 400 mg, and rifabutin 300 mg, given once daily for 7 days. Eradication was confirmed by histology and culture. CYP2C19 status was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Intention-to-treat and per-protocol eradication rates were 77.7% (68.4-85.3) and 83.3% (74.4-90.2). Five patients discontinued prematurely (4.8%). Eradication was achieved in 93.1% of poor/intermediate metabolizers and in 78.8% of homozygous extensive metabolizers (p = .14). Eradication rates in patients with one, two, three, and four or more previous failures were 78.3%, 89.6%, 68.6%, and 88.9%, respectively (p = .21). The regimen was effective in seven of nine patients who previously failed quadruple therapy. Post-treatment resistance to moxifloxacin and rifabutin was detected in two (12.5%) and five (31%) patients after treatment failure. CONCLUSION: Once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin is a promising, safe, and convenient regimen for rescue therapy of H. pylori infection that may serve as a valuable alternative to quadruple therapy, particularly for patients with intolerance to amoxicillin.
Assuntos
Antibacterianos/uso terapêutico , Compostos Aza/uso terapêutico , Farmacorresistência Bacteriana , Esomeprazol/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Quinolinas/uso terapêutico , Rifabutina/uso terapêutico , Adulto , Idoso , Antibacterianos/farmacologia , Hidrocarboneto de Aril Hidroxilases/genética , Compostos Aza/administração & dosagem , Claritromicina/farmacologia , Citocromo P-450 CYP2C19 , Quimioterapia Combinada , Esomeprazol/administração & dosagem , Feminino , Fluoroquinolonas , Mucosa Gástrica/patologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Metronidazol/farmacologia , Pessoa de Meia-Idade , Oxigenases de Função Mista/genética , Moxifloxacina , Polimorfismo de Fragmento de Restrição , Estudos Prospectivos , Quinolinas/administração & dosagem , Rifabutina/administração & dosagemRESUMO
BACKGROUND AND AIMS: Failed primary anti-Helicobacter pylori therapy results in a high rate of antimicrobial resistance. This necessitates a search for new regimens to cure H. pylori infection. The aim of this study was to evaluate the efficacy and tolerability of a new levofloxacin-containing 7-day triple therapy and to compare it with that of standard French triple therapy in patients with known H. pylori susceptibility to MET (metronidazole) and CLA (clarithromycin). PATIENTS AND METHODS: Sixty-one patients with documented antibiotic sensitivity (E-test) and an indication for anti-H. pylori treatment based on the Maastricht Consensus 2/2000 guidelines were randomized to receive either esomeprazole 2 x 40 mg, levofloxacin 2 x 500 mg, and amoxicillin 2 x 1 g for 7 days (ELA, n = 30), or esomeprazole 2 x 20 mg, clarithromycin 2 x 500 mg, and amoxicillin 2 x 1 g for 7 days (ECA, n = 31). A cure check was performed 4-6 weeks after conclusion of therapy. RESULTS: Sixty-one patients were randomized to the two treatment groups. Twenty-eight of 30 patients of the ELA group were available for per-protocol (PP) analysis, of whom 26 (92.9% CI: 76-99%; intention-to-treat [ITT] analysis 86.7% CI: 68-96%) became H. pylori negative compared with 26 of the 31 patients of the ECA group (83.9%, CI: 66-93% both PP and ITT analyses). Five patients of the ELA group showed CLA resistance, three of whom also showed MET resistance, and all five were treated successfully. Two patients with levofloxacin-resistant strains, one in each group, were cured. Both regimens were generally well tolerated with minor adverse events being seen in 15 patients (51.7%) of the ELA group and in 13 (40.6%) of the ECA group. None of the patients discontinued treatment prematurely due to adverse events. CONCLUSION: The data of this pilot study suggest a better than 80% efficacy of the new 7-day levofloxacin triple therapy, which is within the range of the French triple therapy in patients with MET- and CLA-susceptible strains. The data suggest that the new levofloxacin triple therapy may also be an option in patients with MET- and CLA-resistant H. pylori strains.
Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Adulto , Idoso , Amoxicilina/efeitos adversos , Amoxicilina/uso terapêutico , Antibacterianos/efeitos adversos , Claritromicina/farmacologia , Relação Dose-Resposta a Droga , Esomeprazol/efeitos adversos , Esomeprazol/uso terapêutico , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Levofloxacino , Masculino , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ofloxacino/efeitos adversos , Ofloxacino/uso terapêutico , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: Failure of primary anti-H. pylori therapy results in a high rate of antimicrobial resistance. Here, we investigated the efficacy of high-dose dual therapy and quadruple therapy as salvage treatments for eradication of H. pylori resistant to both metronidazole and clarithromycin. PATIENTS AND METHODS: Patients with at least one treatment failure and infected with H. pylori resistant to both metronidazole and clarithromycin, were randomized to receive either omeprazole 4 x 40 mg and amoxicillin 4 x 750 mg; or omeprazole 2 x 20 mg, bismuthcitrate 4 x 107 mg, metronidazole 4 x 500 mg and tetracycline 4 x 500 mg. Both regimens were given for 14 days. In cases of persistent infection, a cross-over therapy was performed. RESULTS: Eighty-four patients were randomized. Cure of H. pylori infection was achieved in 31 patients after dual therapy and in 35 patients after quadruple therapy (per protocol: 83.8% (95% CI, 67.9-93.8) and 92.1% (95% CI, 78.6-98.3), respectively (p=0.71); intention to treat: 75.6% (95% CI: 59.7-87.6) and 81.4% (95% CI: 66.6-91.6), respectively (p=0.60)). Cross-over therapy was performed in six of nine patients, four of whom were cured of the infection. CONCLUSION: Both high-dose dual therapy and quadruple therapy are effective in curing H. pylori infection resistant to both metronidazole and clarithromycin in patients who experienced previous treatment failures.