RESUMO
BACKGROUND: The success rate of current anti-Helicobacter pylori triple therapies in now generally 80% or less. Sequential therapy has proved superior. AIM: To test a new sequential therapy for H. pylori eradication. METHODS: This was a pilot study of a sequential therapy consisting of 40 mg of esomeprazole and 1 g amoxicillin t.d.s., for 12 days. On days 6 through 12 gatifloxacin (400 mg in the morning) was added. Outcome was accessed 4 or more weeks after ending antibiotic therapy. Both naive and treatment failures were eligible. RESULTS: Thirty patients were entered in the study. One was lost to follow-up and one stopped early because of side effects. The success rate intention-to-treat was 80% (95% CI: 61-92%). The per-protocol eradication rate was 85.7% (95% CI: 67-95%); two of the four failures had pre-treatment gatifloxacin-resistant H. pylori. Side effects were reported by 13 patients (46%) and were generally mild with diarrhoea being most common (n = 6). Only one patient stopped medicine because of side effects of dizziness (severe) and diarrhoea (mild). CONCLUSIONS: Sequential therapy using the combination of a high dose of proton-pump inhibitor and amoxicillin followed gatifloxacin was effective, but pre-treatment susceptibility testing may become necessary as fluoroquinolone resistance increases.
Assuntos
Amoxicilina/administração & dosagem , Anti-Infecciosos/administração & dosagem , Esomeprazol/administração & dosagem , Fluoroquinolonas/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Amoxicilina/efeitos adversos , Anti-Infecciosos/efeitos adversos , Protocolos Clínicos , Esquema de Medicação , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Esomeprazol/efeitos adversos , Feminino , Fluoroquinolonas/efeitos adversos , Gatifloxacina , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Antibiotic resistance and duration of therapy influence the success of proton-pump inhibitor-containing Helicobacter pylori eradication therapy. Clarithromycin resistance is associated with treatment failure. AIM: To examine the success of a 7-day rabeprazole-clarithromycin-amoxicillin therapy in the study population. METHODS: Adults from Ciudad Juarez with H. pylori infections identified by culture or histology received rabeprazole 20 mg, clarithromycin 0.5 g and amoxicillin 1 g, each b.d. for 7 days. Outcome was assessed by 13C-urea breath test carried out 4+ weeks after treatment. RESULTS: A total of 111 patients were enrolled and evaluated by urea breath test; 102 completed the full 7 days therapy. Two deviated from protocol, and five stopped because of adverse events. The cure rate (intention-to-treat) was 85% (95% CI: 78-91%); the per-protocol cure rate was 85% (95% CI: 78-91%). Side-effects were not serious and only 6.6% of those with adverse events stopped medication. Only three isolates were clarithromycin-resistant and none was cured. Compliance explained most of the successes. CONCLUSIONS: In the study population a 7-day rabeprazole triple eradication therapy was both effective and well-tolerated. Clarithromycin resistance was uncommon. We observed a slightly better outcome but consistent with results from recent large studies in US populations.
Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Benzimidazóis/uso terapêutico , Claritromicina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Omeprazol/análogos & derivados , 2-Piridinilmetilsulfinilbenzimidazóis , Adolescente , Adulto , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Benzimidazóis/efeitos adversos , Claritromicina/efeitos adversos , Farmacorresistência Bacteriana , Quimioterapia Combinada , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/efeitos adversos , Omeprazol/uso terapêutico , Cooperação do Paciente , Projetos Piloto , Rabeprazol , Falha de Tratamento , Resultado do TratamentoRESUMO
BACKGROUND: Current anti-Helicobacter pylori treatment regimens are costly and because of the increasing antibiotic resistance, are becoming ineffective. AIM: To evaluate a triple-layer tablet containing 100 mg bismuth subcitrate, 250 mg metronidazole, and 250 mg tetracycline in a single triple-layer tablet. METHODS: H. pylori-infected adult patients received bismuth-metronidazole-tetracycline (two tablets, t.d.s.) and ranitidine (300 mg) once daily for 14 days. Efficacy was determined using 13C-urea breath testing. RESULTS: Thirty-three of 35 enrolled patients were available for evaluation; using the protocol-specified modified intention-to-treat analysis, five failed treatment, two were lost to follow-up (cure rate per-protocol = 85.7%, intention-to-treat = 78.7%). The cure rate among metronidazole-susceptible strains was 100% (22 of 22) (95% confidence interval 84-100%) compared with 55% (five of nine intention-to-treat) (95% confidence interval 21-86%) among metronidazole-resistant strains. In four cases, therapy was truncated at 4-7 days because of side-effects; yet the treatment was effective in three. The three metronidazole-susceptible but clarithromycin-resistant infections were cured. CONCLUSION: This novel triple-layer tablet combination therapy was effective in all patients with metronidazole-susceptible H. pylori and many of those with resistant organisms. A greater degree of acid suppression may further improve effectiveness.
Assuntos
Antiácidos/administração & dosagem , Anti-Infecciosos/administração & dosagem , Antiulcerosos/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Compostos Organometálicos/administração & dosagem , Ranitidina/administração & dosagem , Adolescente , Adulto , Idoso , Antiácidos/efeitos adversos , Farmacorresistência Bacteriana , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metronidazol/administração & dosagem , Metronidazol/efeitos adversos , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Cooperação do Paciente , Projetos Piloto , Ranitidina/efeitos adversos , Comprimidos , Tetraciclina/administração & dosagem , Tetraciclina/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Helicobacter pylori associated gastric cancer arises via a multistage process, with atrophic gastritis being the precursor lesion. Helicobacter pylori is typically acquired in childhood, yet little is known of the prevalence of atrophic gastritis in childhood. AIM: To study atrophic gastritis among children from countries with high gastric cancer incidence. METHODS: Sections from topographically mapped gastric biopsy specimens from children undergoing clinically indicated endoscopy in Korea and Colombia were evaluated using visual analogue scales. Atrophy was defined as loss of normal glandular components, including replacement with fibrosis, intestinal metaplasia (IM), and/or pseudopyloric metaplasia of the corpus (identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum). RESULTS: One hundred and seventy three children, 58 from Korea (median age, 14 years) and 115 from Colombia (median age, 13 years), were studied. Helicobacter pylori was present in 85% of Colombian children versus 17% of Korean children (p<0.01). Atrophic mucosa near the antrum-corpus border was present in 16% of children, primarily as pseudopyloric metaplasia (31%, IM; 63%, pseudopyloric metaplasia; 6%, both). The median age of children with corpus atrophy was 15 (range, 7-17) years. CONCLUSION: Gastric atrophy occurs in H pylori infected children living in countries with high gastric cancer incidence. Identification and characterisation of the natural history of H pylori gastritis requires targeted biopsies to include the lesser and greater curve of the corpus, starting just proximal to the anatomical antrum-corpus junction, in addition to biopsies targeting the antrum and cardia.
Assuntos
Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori/isolamento & purificação , Adolescente , Biópsia , Criança , Pré-Escolar , Colômbia , Feminino , Mucosa Gástrica/patologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Gastroscopia , Infecções por Helicobacter/patologia , Humanos , Coreia (Geográfico) , Masculino , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Antro Pilórico/microbiologia , Antro Pilórico/patologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: In the USA, atrophic gastritis and gastric cancer are rare, whereas gastro-oesophageal reflux disease (GERD) is common. Infection with Helicobacter pylori, especially a CagA positive strain, is unusual in patients with GERD/Barrett's oesophagus in the USA. AIM: To examine the relation between Barrett's oesophagus and CagA positive H pylori in Colombia, a country with a high prevalence of CagA positive H pylori associated atrophic gastritis and gastric cancer. METHODS: Helicobacter pylori and CagA status was determined among Colombian patients with long segment Barrett's oesophagus and a control group with simple H pylori gastritis. Helicobacter pylori status was determined using a triple stain and CagA status was determined by immunohistochemistry using a specific rabbit anti-CagA serum. RESULTS: Gastric and oesophageal mucosal biopsies were obtained from 51 patients--39 men (mean age, 57.8 years; SD, 13.1) and 12 women (mean age, 51.8 years; SD, 14.4)--with documented long segment Barrett's oesophagus. The results were compared with 24 Colombian patients with H pylori gastritis without oesophageal disease. Thirty two patients with Barrett's oesophagus had active H pylori infection. CagA status was evaluated in a subset of 23 H pylori infected patients with Barrett's oesophagus, and was positive in eight of these patients compared with 19 of 24 controls (p = 0.01). CONCLUSIONS: Although most Colombian patients with Barrett's oesophagus had H pylori infection, CagA positive infections were unusual. These data illustrate how consistent corpus inflammation reduces acid secretion, which prevents Barrett's oesophagus among those with abnormal gastro-oesophageal reflux barriers.
Assuntos
Antígenos de Bactérias/análise , Proteínas de Bactérias/análise , Esôfago de Barrett/microbiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/química , Neoplasias Gástricas/microbiologia , Adulto , Idoso , Animais , Esôfago de Barrett/etnologia , Esôfago de Barrett/patologia , Colômbia/epidemiologia , Feminino , Mucosa Gástrica/patologia , Gastrite/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Humanos , Masculino , Metaplasia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/etnologia , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Prevalência , Coelhos , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Antisecretory therapy may exacerbate Helicobacter pylori corpus gastritis. The rate and mechanism(s) remain unknown. AIM: To investigate the early events in proton pump inhibitor therapy on antral and corpus H. pylori gastritis. METHODS: Nine H. pylori-infected volunteers underwent gastric biopsy with jumbo forceps for culture and histology. Histology was scored in the range 0-5 using a visual analogue scale. The depth of inflammation in gastric pits was scored in the range 1-3 (superficial or less than one-third, one-third to two-thirds and greater than two-thirds of the gastric pit, respectively). Tissue interleukin-1 beta and interleukin-8 levels were measured by enzyme-linked immunoabsorbent assay. Omeprazole, 20 mg b.d., was given for 6.5 days and biopsies were repeated on day 7. RESULTS: Proton pump inhibitor therapy resulted in a fall in H. pylori density in the antrum and corpus. Inflammation and tissue levels of interleukin-8 and interleukin-1 beta decreased in the antrum and increased in the corpus mucosa. There was a significant increase in the depth of inflammation to include the proliferative zone in the corpus. CONCLUSIONS: Within 1 week of starting proton pump inhibitor therapy, there was a marked extension of corpus inflammation into the gastric pit and an increase in corpus mucosal interleukin-1 beta and interleukin-8 levels. H. pylori eradication should be considered for all patients receiving long-term antisecretory therapy.
Assuntos
Antiulcerosos/efeitos adversos , Gastrite/induzido quimicamente , Infecções por Helicobacter , Helicobacter pylori , Omeprazol/efeitos adversos , Inibidores da Bomba de Prótons , Adulto , Feminino , Gastrite/microbiologia , Humanos , MasculinoRESUMO
AIM: To compare H2-receptor antagonists and proton pump inhibitors as adjuvants to triple therapy for Helicobacter pylori eradication. METHODS: H. pylori-infected patients with peptic ulcer were randomized to receive either 300 mg nizatidine or 30 mg lansoprazole plus 1 g amoxicillin and 500 mg clarithromycin taken b.d. for 7 days. H. pylori eradication was assessed 4 weeks after therapy. Using meta-analytical techniques, we combined the results of this study with other randomized controlled comparisons of H2-receptor antagonists and proton pump inhibitors as adjuvants to triple therapy. RESULTS: One hundred and one patients were randomized. H. pylori eradication was 94% (47/50) [95% confidence interval (CI), 83-99%] (intention-to-treat) in the H2-receptor antagonist group vs. 86% (44/51) (95% CI, 74-94%) in the proton pump inhibitor group (P = 0.3). There has been a total of 12 similar studies (1415 patients). The overall efficacy was similar in intention-to-treat analysis: 78% (549/701) with H2-receptor antagonists vs. 81% (575/714) with proton pump inhibitors (odds ratio, 0.86; 95% CI, 0.66-1.12). A non-significant trend favouring H2-receptor antagonist (79% vs. 69%; odds ratio, 1.14; 95% CI, 0.76-1.71; P = 0.5) was seen in the comparison of clarithromycin-containing regimens. In contrast, in non-clarithromycin-containing trials, there was a slight, but significant, advantage with proton pump inhibitors (85% vs. 78%; odds ratio, 0.64; 95% CI, 0.45-0.92; P = 0.02). CONCLUSION: Overall, proton pump inhibitor and H2-receptor antagonist antisecretory agents appear to be similarly effective as adjuvants for H. pylori triple therapy. It is unlikely that the direct anti-H. pylori effect of proton pump inhibitors is responsible for their ability to enhance anti-H. pylori therapy.
Assuntos
Antiulcerosos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Inibidores da Bomba de Prótons , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Lansoprazol , Masculino , Pessoa de Meia-Idade , Nizatidina/uso terapêutico , Omeprazol/análogos & derivados , Omeprazol/uso terapêuticoRESUMO
BACKGROUND: Quadruple therapy provided inadequate eradication rate when given twice-a-day at breakfast and evening meals. AIM: To test twice daily (mid-day and evening) quadruple therapy for Helicobacter pylori eradication. METHODS: This was a single-centre pilot study in which H. pylori-infected (positive histology and culture and RUT) patients were given 2 x 250 mg of metronidazole and 2 x 250 mg of tetracycline, two Pepto-Bismol tablets, plus one 20 mg rabeprazole tablet twice-a-day for 14 days. H. pylori status was confirmed 4 or more weeks after the end of therapy. RESULTS: Thirty-seven patients including 3 with peptic ulcer disease, 19 asymptomatic infected, 4 GERD, and 11 with NUD. Mid-day quadruple therapy was successful in 92.3% (95% CI: 79-98%) including 96.2% of those with metronidazole-susceptible strains, and in 83.3% (10/12) of those with metronidazole-resistant H. pylori. Compliance was 100% by pill count except in one individual who stopped medication after 12 days because of side-effects and who failed therapy. Moderate or greater side-effects were experienced by five patients. CONCLUSION: Twice-a-day, mid-day, quadruple therapy proved effective using the combination of bismuth subsalicylate and rabeprazole instead of bismuth subcitrate and omeprazole. Detailed studies of different formulations (e.g. 2 x 250 mg versus 1 x 500 mg of metronidazole or tetracycline) and timing of administration (breakfast and evening meal versus mid-day and evening meals) may result in significant improvements in H. pylori eradication regimens.
Assuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , 2-Piridinilmetilsulfinilbenzimidazóis , Antiácidos/administração & dosagem , Antiácidos/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Antiulcerosos/administração & dosagem , Antiulcerosos/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Bismuto/administração & dosagem , Bismuto/efeitos adversos , Esquema de Medicação , Farmacorresistência Bacteriana , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metronidazol/administração & dosagem , Metronidazol/efeitos adversos , Pessoa de Meia-Idade , Omeprazol/análogos & derivados , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/efeitos adversos , Cooperação do Paciente , Projetos Piloto , Estudos Prospectivos , ATPases Translocadoras de Prótons/antagonistas & inibidores , Rabeprazol , Salicilatos/administração & dosagem , Salicilatos/efeitos adversos , Tetraciclina/administração & dosagem , Tetraciclina/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: A number of Helicobacter pylori outer membrane proteins (OMPs) undergo phase variations. This study examined the relation between OMP phase variations and clinical outcome. METHODS: Expression of H pylori BabA, BabB, SabA, and OipA proteins was determined by immunoblot. Multiple regression analysis was performed to determine the relation among OMP expression, clinical outcome, and mucosal histology. RESULTS: H pylori were cultured from 200 patients (80 with gastritis, 80 with duodenal ulcer (DU), and 40 with gastric cancer). The most reliable results were obtained using cultures from single colonies of low passage number. Stability of expression with passage varied with OipA > BabA > BabB > SabA. OipA positive status was significantly associated with the presence of DU and gastric cancer, high H pylori density, and severe neutrophil infiltration. SabA positive status was associated with gastric cancer, intestinal metaplasia, and corpus atrophy, and negatively associated with DU and neutrophil infiltration. The Sydney system underestimated the prevalence of intestinal metaplasia/atrophy compared with systems using proximal and distal corpus biopsies. SabA expression dramatically decreased following exposure of H pylori to pH 5.0 for two hours. CONCLUSIONS: SabA expression frequently switched on or off, suggesting that SabA expression can rapidly respond to changing conditions in the stomach or in different regions of the stomach. SabA positive status was inversely related to the ability of the stomach to secrete acid, suggesting that its expression may be regulated by changes in acid secretion and/or in antigens expressed by the atrophic mucosa.
Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Gastroenteropatias/microbiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/metabolismo , Adenocarcinoma/microbiologia , Biópsia , Úlcera Duodenal/microbiologia , Feminino , Mucosa Gástrica/patologia , Gastrite/microbiologia , Genes Bacterianos , Genótipo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Humanos , Concentração de Íons de Hidrogênio , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fenótipo , Neoplasias Gástricas/microbiologiaRESUMO
BACKGROUND: A reliable challenge model is needed to evaluate Helicobacter pylori vaccine candidates. METHODS: A cag pathogenicity island negative, OipA positive, multiple antibiotic susceptible strain of H pylori obtained from an individual with mild gastritis (Baylor strain 100) was used to challenge volunteers. Volunteers received 40 mg of famotidine at bedtime and 10(4)-10(10) cfu of H pylori in beef broth the next morning. Infection was confirmed by (13)C urea breath test ((13)C-UBT), culture, and histology. Eradication therapy was given four or 12 weeks post challenge and eradication was confirmed by at least two separate UBTs, as well as culture and histology. RESULTS: Twenty subjects (nine women and 11 men; aged 23-33 years) received a H pylori challenge. Eighteen (90%) became infected. Mild to moderate dyspeptic symptoms occurred, peaked between days 9 and 12, and resolved. Vomitus from one subject contained >10(3) viable/ml H pylori. By two weeks post challenge gastric histology showed typical chronic H pylori gastritis with intense acute and chronic inflammation. The density of H pylori (as assessed by cfu/biopsy) was similarly independent of the challenge dose. A minimal infectious dose was not found. Gastric mucosal interleukin 8 levels increased more than 20-fold by two weeks after the challenge. CONCLUSION: Challenge reliably resulted in H pylori infection. Infection was associated with typical H pylori gastritis with intense polymorphonuclear cell infiltration and interleukin 8 induction in gastric mucosa, despite absence of the cag pathogenicity island. Experimental H pylori infection is one of the viable approaches to evaluate vaccine candidates.