RESUMO
BACKGROUND: Most treatments deemed effective for Helicobacter pylori eradication in developed countries are less effective in developing countries. Regimens containing clarithromycin, metronidazole, and amoxicillin seem efficacious despite antibiotic resistance, and may be a viable option in developing countries. MATERIALS AND METHODS: We evaluated the efficacy of a 14-day regimen with 500 mg clarithromycin b.i.d., 500 mg metronidazole t.i.d., and 500 mg amoxicillin t.i.d. (with and without a proton pump inhibitor), and a 10-day regimen containing 500 mg clarithromycin b.i.d., 1 g amoxicillin b.i.d., and 20 mg omeprazole b.i.d. in Pasto, Colombia, using a randomized, single-blind design stratified by presence of atrophic gastritis. RESULTS: H. pylori was eradicated in 86.8% and 85.3% of the participants randomized to a clarithromycin-metronidazole-amoxicillin and clarithromycin-amoxicillin-omeprazole regimens, respectively (p = .79). Per-protocol analyses indicated greater efficacy for the clarithromycin-metronidazole-amoxicillin regimen (97%) versus the clarithromycin-amoxicillin-omeprazole regimen (86%) (p = .04), particularly for participants with atrophic gastritis (clarithromycin-metronidazole-amoxicillin = 100%, clarithromycin-amoxicillin-omeprazole = 81%; p = .02). Adverse events were mild, but adverse event-related non-compliance was reported more often for regimens containing clarithromycin, metronidazole, and amoxicillin. CONCLUSIONS: Our results suggest that an eradication rate of > 85% can be achieved with 14-day clarithromycin, metronidazole, and amoxicillin and 10-day clarithromycin, amoxicillin, and omeprazole regimens in Pasto, Colombia. The regimens containing clarithromycin, metronidazole, and amoxicillin appear to be superior to the clarithromycin, amoxicillin, and omeprazole regimen for compliant participants and those with atrophic gastritis. Our findings provide treatment options for a population in a developing country with a high prevalence of H. pylori infections and antibiotic resistance.
Assuntos
Amoxicilina/administração & dosagem , Claritromicina/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Metronidazol/administração & dosagem , Adulto , Idoso , Amoxicilina/efeitos adversos , Antibacterianos/administração & dosagem , Claritromicina/efeitos adversos , Estudos de Coortes , Colômbia , Países em Desenvolvimento , Quimioterapia Combinada , Feminino , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Masculino , Metronidazol/efeitos adversos , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do TratamentoRESUMO
It has been proposed that eradication of Helicobacter pylori infection is a sound strategy for gastric cancer prevention. Several factors including smoking have been associated to treatment failure rates. This study aimed to evaluate the smoking effect on the efficacy of H. pylori therapy, as well as on the histological parameters in the gastric mucosa from subjects from a high gastric cancer risk area. Two-hundred-sixty-four Colombian subjects with gastric precancerous lesions who participated in a chemoprevention trial, received anti-H. pylori treatment at baseline and had data recorded on cigarette use, were included in this study. A detailed histopathological assessment of the gastric mucosa was performed in biopsies taken before any intervention. H. pylori eradication was assessed in gastric biopsies at 36 months post-treatment. The overall eradication rate was 52.3%; rates of 41.3% and 57.1% were observed for active-smokers and non-smokers, respectively. Multivariate logistic regression analysis showed that smokers had a 2-fold higher probability of failure in Helicobacter pylori eradication than non-smokers (OR: 2.0; 95% CI: 1.01-3.95). At baseline, active-smokers had a higher score of intestinal metaplasia compared to non-smokers. In the corpus mucosa, active-smokers showed lower scores of H. pylori density, total inflammation, neutrophil infiltration, and mucus depletion than non-smokers. In the antrum, no significant differences were observed between active-smokers and non-smokers. In summary, in patients who smoked, H. pylori treatment was less effective. Smoking cessation may benefit H. pylori eradication rates.
Assuntos
Mucosa Gástrica/microbiologia , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Fumar/efeitos adversos , Amoxicilina/uso terapêutico , Anti-Infecciosos/uso terapêutico , Bismuto/uso terapêutico , Colômbia , Quimioterapia Combinada , Feminino , Seguimentos , Mucosa Gástrica/patologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Humanos , Masculino , Metaplasia , Metronidazol/uso terapêutico , Compostos Organometálicos/uso terapêutico , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/microbiologia , Análise de Regressão , Salicilatos/uso terapêutico , Falha de TratamentoRESUMO
It has been proposed that eradication of Helicobacter pylori infection is a sound strategy for gastric cancer prevention. Several factors including smoking have been associated to treatment failure rates. This study aimed to evaluate the smoking effect on the efficacy of H. pylori therapy, as well as on the histological parameters in the gastric mucosa from subjects from a high gastric cancer risk area. Two-hundred-sixty-four Colombian subjects with gastric precancerous lesions who participated in a chemoprevention trial, received anti- H. pylori treatment at baseline and had data recorded on cigarette use, were included in this study. A detailed histopathological assessment of the gastric mucosa was performed in biopsies taken before any intervention. H. pylori eradication was assessed in gastric biopsies at 36 months post-treatment. The overall eradication rate was 52.3%; rates of 41.3% and 57.1% were observed for active-smokers and non-smokers, respectively. Multivariate logistic regression analysis showed that smokers had a 2-fold higher probability of failure in Helicobacter pylori eradication than non-smokers (OR: 2.0; 95% CI: 1.01-3.95). At baseline, activesmokers had a higher score of intestinal metaplasia compared to non-smokers. In the corpus mucosa, active-smokers showed lower scores of H. pylori density, total inflammation, neutrophil infiltration, and mucus depletion than non-smokers. In the antrum, no significant differences were observed between active-smokers and non-smokers. In summary, in patients who smoked, H. pylori treatment was less effective. Smoking cessation may benefit H. pylori eradication rates.
La erradicación del Helicobacter pylori ha sido propuesta como medida promisoria en la prevención del cáncer gástrico. Varios factores, incluyendo el tabaquismo, se asocian con la falla del tratamiento. El objetivo de este estudio fue evaluar el efecto del tabaquismo en la eficacia del tratamiento anti-H. pylori y en la histología gástrica en residentes de una zona de alto riesgo de cáncer gástrico. Este estudio incluyó 264 sujetos colombianos con lesiones gástricas preneoplásicas que participaron en un estudio de quimioprevención, recibieron tratamiento anti-H. pylori al ingreso, y proveyeron información sobre tabaquismo. Se realizó un detallado análisis histopatológico en las biopsias colectadas al ingreso. La erradicación de la infección fue evaluada en las biopsias gástricas a los 36 meses post-tratamiento. El porcentaje general de erradicación fue de 52.3%, con proporciones de 41.3% y 57.1% en fumadores activos y no fumadores, respectivamente. El análisis de regresión logística múltiple mostró que el riesgo de presentar falla al tratamiento fue doble en fumadores en comparación con los no fumadores (OR: 2.0; 95% CI: 1.01-3.95). Los fumadores presentaron un mayor índice de metaplasia intestinal comparado con los no fumadores. En la mucosa del cuerpo gástrico los fumadores mostraron menores índices de colonización por H. pylori, inflamación total, infiltración de neutrófilos y depleción de moco que los no fumadores. En el antro no se observaron diferencias significacomtivas entre ambos grupos. En conclusión, el tratamiento anti-H. pylori fue menos efectivo en sujetos fumadores. La cesación del consumo de tabaco puede beneficiar las tasas de erradicación del H. pylori.
Assuntos
Humanos , Masculino , Feminino , Bismuto/uso terapêutico , Mucosa Gástrica/microbiologia , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Compostos Organometálicos/uso terapêutico , Salicilatos/uso terapêutico , Fumar/efeitos adversos , Amoxicilina/uso terapêutico , Anti-Infecciosos/uso terapêutico , Colômbia , Quimioterapia Combinada , Seguimentos , Mucosa Gástrica/patologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Metaplasia , Metronidazol/uso terapêutico , Lesões Pré-Cancerosas , Análise de Regressão , Falha de TratamentoAssuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Dispepsia/tratamento farmacológico , Dispepsia/etiologia , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/etiologia , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/etiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/fisiopatologia , Humanos , Metaplasia/tratamento farmacológico , Metaplasia/etiologia , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/etiologiaRESUMO
OBJECTIVES: Helicobacter pylori causes gastric adenocarcinoma. We assessed the success of H. pylori eradication therapy in a medically underserved population in Chiapas, Mexico, that is at high risk for gastric cancer risk. METHODS: Healthy volunteers with both antibodies to CagA and gastrin levels > or = 25 ng/ml were randomly assigned to receive either a combination of omeprazole, amoxicillin, and clarithromycin or matched placebo for 1 wk. Endoscopy with seven biopsies was performed at baseline, at 6 wk, and 1 yr after treatment. Treatment success was defined as loss of H. pylori by histological analysis. Cure was assessed using change in serology based on the standardized absorbance of a H. pylori ELISA. RESULTS: H. pylori eradication rates were high (intent-to-treat analysis: 76.3% [95% CI = 68.7-84.0%] after 6 wk and 76.1% [95% CI = 67.7-84.6%] after 1 yr; per protocol analysis: 77.8% [95% CI = 70.1-85.4%] after 6 wk and 75.2% [95% CI = 66.5-84.0%] after 1 yr). Nine subjects on active treatment and one subject on placebo who were without H. pylori at 6 wk were infected at 1 yr (recurrence rates 10.7% and 33.3%, respectively, p = 0.31). Median changes in standardized absorbance at 1 yr were 47% and 1% for successfully and unsuccessfully treated patients, respectively. A 10% decline in standardized absorbance after 1 yr had 84% sensitivity and 100% specificity for H. pylori eradication. CONCLUSIONS: Even with a short course of treatment against H. pylori, a high rate of eradication rate can be achieved in populations at high risk for stomach cancer. Serum antibodies are useful in assessing efficacy of therapy.
Assuntos
Adenocarcinoma/etiologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Neoplasias Gástricas/etiologia , Adulto , Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Antiulcerosos/administração & dosagem , Anticorpos Antibacterianos/análise , Antígenos de Bactérias/análise , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Claritromicina/administração & dosagem , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Feminino , Gastrinas/sangue , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/metabolismo , Humanos , Imunoglobulina G/análise , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Penicilinas/administração & dosagem , Lesões Pré-Cancerosas/tratamento farmacológico , Curva ROC , Recidiva , Fatores de RiscoAssuntos
Gastrite Atrófica/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/genética , Amoxicilina/uso terapêutico , Antiácidos/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Quimioprevenção , Colômbia , Seguimentos , Gastrite Atrófica/tratamento farmacológico , Genótipo , Helicobacter pylori/patogenicidade , Humanos , Metronidazol/uso terapêutico , Compostos Organometálicos/uso terapêutico , Penicilinas/uso terapêutico , Lesões Pré-Cancerosas/prevenção & controle , Salicilatos/uso terapêutico , Neoplasias Gástricas/prevenção & controle , Falha de Tratamento , VirulênciaRESUMO
A randomized chemoprevention trial on precancerous lesions of the stomach is being conducted in Tachira State, Venezuela. The aims of the study are to evaluate the efficacy of vitamin supplementation in preventing the progression rate of precancerous lesions. Here we report on the pilot phase of the study in which two antioxidant preparations were evaluated on their ability to raise antioxidant levels in plasma and in gastric juice. The study aimed also to determine the antibiotic sensitivity profiles of Helicobacter pylori isolates prevalent in the area. Forty-three subjects with precancerous lesions (chronic gastritis, chronic atrophic gastritis, intestinal metaplasia and dysplasia) of the stomach were randomized to one of two antioxidant treatments. Treatment 1 (250 mg of standard vitamin C, 200 mg of vitamin E and 6 mg of beta-carotene three times a day) or treatment 2 (150 mg of standard vitamin C, 500 mg of slow release vitamin C, 75 mg of vitamin E and 15 mg of beta-carotene once a day) for 7 days. Blood levels of total vitamin C, beta-carotene and alpha-tocopherol and gastric juice levels of ascorbic acid and total vitamin C were measured before and after treatment on day 8. Both treatments increased the plasma levels of total vitamin C, beta-carotene and alpha-tocopherol/cholesterol but not those of ascorbic acid or total vitamin C in gastric juice. Treatment 1 was the best choice and resulted in a greater increase in the plasma levels of beta-carotene and alpha-tocopherol. H. pylori was cultured from 90% of the gastric biopsies; 35 isolates were identified which were highly resistant to metronidazole, a front-line antibiotic recommended against H. pylori in other settings.