Efficacy of levofloxacin, amoxicillin and a proton pump inhibitor in the eradication of Helicobacter pylori in Brazilian patients with peptic ulcers

OBJECTIVES: The eradication of Helicobacter (H.) pylori allows peptic ulcers in patients infected with the bacteria to be cured. Treatment with the classic triple regimen (proton pump inhibitor, amoxicillin and clarithromycin) has shown decreased efficacy due to increased bacterial resistance to clarithromycin. In our country, the eradication rate by intention to treat with this regimen is 83%. In Brazil, a commercially available regimen for bacterial eradication that uses levofloxacin and amoxicillin with lansoprazole is available; however, its efficacy is not known. Considering that such a treatment may be an alternative to the classic regimen, we aimed to verify its efficacy in H. pylori eradication. METHODS: Patients with peptic ulcer disease infected with H. pylori who had not received prior treatment were treated with the following regimen: 30 mg lansoprazole bid, 1,000 mg amoxicillin bid and 500 mg levofloxacin, once a day for 7 days. RESULTS: A total of 66 patients were evaluated. The patients’ mean age was 52 years, and women comprised 55% of the sample. Duodenal ulcers were present in 50% of cases, and gastric ulcers were present in 30%. The eradication rate was 74% per protocol and 73% by intention to treat. Adverse effects were reported by 49 patients (74%) and were mild to moderate, with a prevalence of diarrhea complaints. CONCLUSIONS: Triple therapy comprising lansoprazole, amoxicillin and levofloxacin for 7 days for the eradication of H. pylori in Brazilian peptic ulcer patients showed a lower efficacy than that of the classic triple regimen. .

Helicobacter pylori antibiotic resistance in Brazil: clarithromycin is still a good option / Resistência do Helicobacter pylori aos antibióticos no Brasil: a claritromicina ainda é uma boa opção

CONTEXT: The antibiotic susceptibility is the cornerstone for the eradication therapies of Helicobacter pylori. OBJECTIVES: To evaluate the prevalence of primary resistance of H. pylori was evaluated in an urban Brazilian population. METHODS:H. pylori isolates were obtained from patients submitted to an upper gastrointestinal endoscopy for the evaluation of dyspeptic symptoms. Biopsies from antrum, corpus and fundus were taken to determine the antibiotic susceptibility of H. pylori isolates. The minimal inhibitory concentration of furazolidone and bismuth were routinely determined by agar dilution method and the minimal inhibitory for amoxicillin, clarithromycin, tetracycline, levofloxacin, and metronidazole were routinely determined with the E-test. RESULTS: Fifty-four patients were included. In vitro antimicrobial susceptibility of H. pylori strains were obtained from 39 patients. Resistance to metronidazole was detected in 20 patients (51 percent), to clarithromycin in 3 patients (8 percent), to levofloxacin in 9 patients (23 percent) and to bismuth in 2 patients (5 percent). There was no observed resistance to amoxicillin, tetracycline or furazolidone. CONCLUSION: Due to the low amoxicillin and clarithromycin resistance observed in this study, therapies using these antimicrobials remain appropriated first-line H. pylori therapy.

CONTEXTO: A susceptibilidade aos antibióticos é a pedra fundamental dos tratamentos de erradicação do Helicobacter pylori. OBJETIVO: Avaliar a prevalência da resistência primária do H. pylori aos antibióticos em uma população urbana do Brasil. MÉTODOS: As cepas do H. pylori foram obtidas de pacientes submetidos a endoscopia digestiva para avaliação de sintomas dispépticos. Biopsias do antro, corpo e fundo gástrico foram realizadas para determinar a susceptibilidade das cepas do H. pylori aos antibióticos. A concentração inibitória mínima da furazolidona e do bismuto foram determinadas rotineiramente pelo método da diluição em Agar e a concentração inibitória mínima da amoxicilina, claritromicina, tetraciclina, levofloxacina e do metronidazol foram determinadas pelo E-test. RESULTADOS: Cinquenta e quarto pacientes foram incluídos no estudo. Destes, a susceptibilidade das cepas do H. pylori in vitro foi determinada em 39 pacientes. Resistência ao metronidazol foi detectada em 20 pacientes (51 por cento), à claritromicina em 3 pacientes (8 por cento), à levofloxacina in 9 pacientes (23 por cento) e ao bismuto em 2 pacientes (5 por cento). não foi observada resistência à amoxicilina, tetraciclina e à furazolidona. CONCLUSÃO: Devido à baixa resistência, observada neste estudo para a amoxicilina e a claritromicina, os tratamentos que usam estes antibióticos permanecem apropriados como esquemas de primeira linha para a erradicação do H. pylori.

Neither genotype nor the gastric colonization site of Helicobacter pylori are predictive factors for the development of erosive esophagitis in patients with peptic ulcer disease, 1 year after eradication / O genótipo e o local no estômago de isolamento do Helicobacter pylori em pacientes com úlcera péptica não são fatores preditivos para o desenvolvimento de esofagite erosiva 1 ano após a erradicação da bactéria

CONTEXT: Whether Helicobacter pylori infection is a protective or predisposing factor for the development of gastroesophageal reflux disease remains controversial. The most virulent strains, such as those expressing the cytotoxin-associated gene A (CagA), and the site of gastric colonization have been correlated with the prevention or development of esophagitis. AIM: To determine the incidence of erosive esophagitis following eradication of H. pylori in patients with peptic ulcer disease and to evaluate the association of erosive esophagitis with virulent strains of H. pylori and the site of gastric colonization. METHODS: Triple therapy with lansoprazole, amoxicillin and clarithromycin was administered to 159 patients with peptic ulcer disease. Endoscopy, histopathology, urease and carbon-14 urea breath tests were performed prior to treatment, at 3 months and 1 year following treatment. Genotyping of H. pylori strains using polymerase chain reaction was performed separately on samples from the corpus and antrum. RESULTS: One year after treatment, 148 successfully treated patients were reevaluated. Twenty-eight patients (19 percent) had erosive esophagitis, classified as Los Angeles grade A in 24 and B in 4. The samples taken from the corpus were CagA-positive in 18 patients (64 percent), while the samples taken from the antrum were CagA-positive in 21 patients (75 percent). CONCLUSIONS: The incidence of erosive esophagitis in peptic ulcer patients who had their H. pylori eradicated was 19 percent. No correlation was found between the gastric site colonized by H. pylori or strains expressing CagA and the prevention or development of erosive esophagitis in patients with peptic ulcer disease, 1 year after infection eradication.

CONTEXTO: É controverso se a infecção pelo Helicobacter pylori é um fator de proteção ou de predisposição para o desenvolvimento da doença de refluxo gastroesofágico. Cepas mais virulentas tais como as que expressam a citotoxina CagA e o local no estômago de infecção pela bactéria, podem estar correlacionados com a prevenção ou desenvolvimento de esofagite. OBJETIVOS: Determinar a incidência de esofagite erosiva após a erradicação do H. pylori em pacientes com úlcera péptica e a sua associação com a virulência das cepas da bactéria e o local no estômago de seu isolamento. MÉTODOS: Um tratamento tríplice com lansoprazol, amoxicilina e claritromicina foi administrado a 159 pacientes com úlcera péptica. Endoscopia digestiva alta, exame histológico, teste rápido da urease e o teste respiratório de uréia com carbono-14 foram realizados antes, 3 meses e 1 ano após o tratamento. A genotipagem das cepas do H. pylori por meio de PCR foi realizada separadamente em amostras obtidas da mucosa do corpo e do antro gástricos. RESULTADOS: Um ano após o tratamento, 148 pacientes curados da infecção foram avaliados: 28 (19 por cento) apresentavam esofagite erosiva, 24 com grau A da classificação de Los Angeles e 4 com grau B. Nas amostras obtidas da mucosa do corpo gástrico, a citotoxina CagA foi positiva em 18 (64 por cento) pacientes com esofagite erosiva, enquanto que nas amostras obtidas do antro gástrico, a citotoxina CagA foi positiva em 21 (75 por cento). CONCLUSÕES: A incidência de esofagite erosiva em pacientes com doença péptico-ulcerosa foi de 19 por cento. Não houve correlação entre o local de isolamento no estômago ou as cepas CagA-positivas do H. pylori e a proteção ou o desenvolvimento de esofagite erosiva, em pacientes com úlcera péptica, 1 ano depois da erradicação da bactéria.

Reinfecção pelo Helicobacter pylori em pacientes brasileiros com úlcera péptica, em seguimento de 5 anos / Helicobacter pylori reinfection in brazilian patients with peptic ulcer disease, a five year follow-up

Introdução: A reinfecção pelo Helicobacter pylori em países em desenvolvimento parece ser maior do que nos países desenvolvidos. O retratamento da bactéria e o controle periódico de cura são necessários, quando elevadas taxas de reinfecção são verificadas. O objetivo do trabalho foi determinar a taxa anual de reinfecção, em pacientes brasileiros com úlcera péptica, num seguimento de cinco anos. Métodos: Pacientes com úlcera péptica, diagnosticada por endoscopia digestiva alta e infecção pelo Helicobacter pylori documentada por histologia, teste da urease, reação em cadeia da polimerase e teste respiratório, foram tratados para erradicação da bactéria. A cura da infecção foi verificada com os mesmos exames, três meses após o término do tratamento. Avaliação clínica e teste respiratório foram realizados aos seis e nove meses. Com um ano de seguimento, endoscopia, exame histológico, teste da urease, reação em cadeia da polimerase e teste respiratório foram novamente realizados. Até o quinto ano de seguimento, foram feitas consultas semestrais e testes respiratórios anuais. Na inclusão dos pacientes e nos reinfectados foram estudados 15 diferentes genes da bactéria. Resultados: Cento e quarenta e sete pacientes foram seguidos: 19 por um ano, oito por dois anos, quatro por três anos, cinco por quatro anos e 98 por cinco anos, num total de 557 pacientes/ano. Não ocorreu reinfecção no primeiro ano. No segundo ano, dois pacientes se reinfectaram, no terceiro quatro pacientes, no quarto três pacientes e no quinto um paciente, num total de 10 reinfecções. A taxa anual de reinfecção por pacientes/ano foi de 1,8%. Conclusão: O Brasil, um país em desenvolvimento com alta prevalência da infecção pelo Helicobacter pylori, apresenta uma taxa de reinfecção semelhante à dos países desenvolvidos.

Introduction: The Helicobacter pylori reinfection rate seems to be higher in developing countries, than in developed ones. If a high reinfection rate is verified, periodical exams and bacterial retreatment would be necessary. The objective of this study was to determine the annual reinfection rate of Helicobacter pylori, in Brazilian patients with peptic ulcer disease, in a five year follow-up. Methods: Patients, with peptic ulcer disease diagnosed by upper digestive endoscopy and Helicobacter pylori infection verified by histological examination, rapid urease test, polymerase chain reaction and urea breath test, were treated for bacterial eradication. The infection cure was determined by the same proceedings, three months after the treatments end. Clinical evaluation and urea breath test were performed at sixth and ninth months of the follow-up. At one year of the follow-up, upper digestive endoscopy, histological examination, rapid urea test, polymerase chain reaction and urea breath test were repeated. Up to the fifth year of follow-up semester clinical evaluation and annual urea breath test were performed. All the patients included in the study and all the reinfected patients were tested for fifteen different genes of the Helicobacter pylori. Results: One hundred and forty-seven patients were followed: nineteen patients for one year, eight patients for two years, four patients for three years, five patients for four years and ninety-eight patients for five years. The total of patients/years follow-up was 557. Reinfection did not occur in the first year of the follow-up. In the second year, two patients became reinfected; in the third year, four patients; in the fourth, three and in the fifth, one patient. The total of reinfected patients was 10. The annual reinfection rate was 1,8%. Conclusion: Brazil, a developing country, presents a high prevalence of Helicobacter pylori infection. Nonetheless, the reinfection rate is similar to the developed countries.

A furazolidone-based quadruple therapy for Helicobacter pylori retreatment in patients with peptic ulcer disease

OBJETIVO: Muitos dos esquemas atualmente usados na erradicação do Helicobacter pylori não conseguem curar a infecção, pela resistência bacteriana ou pela baixa adesão do paciente. Esta condição manterá os riscos de desenvolvimento das potenciais complicações graves da infecção. Este estudo procurou determinar a eficácia e segurança de um esquema quádruplo que associou a furazolidona para o retratamento da infecção pelo H. pylori. MÉTODOS: Pacientes que não alcançaram erradicação em um ou mais tratamentos foram submetidos à endoscopia digestiva alta e dois fragmentos do antro e do corpo foram retirados para exame histológico e de urease. Receberam então 20mg de omeprazol, 240mg de sub-citrato de bismuto, 500mg de tetraciclina e 200mg de furazolidona duas vezes ao dia por 7 dias. O sucesso terapêutico foi determinado pela negativação de nova biópsia endoscópica, após 8 semanas do tratamento. RESULTADOS: Sessenta e dois pacientes foram incluídos, cinqüenta e oito completaram o estudo. Por protocolo, 67% (39/58) dos pacientes conseguiram a erradicação da bactéria. Efeitos adversos leves foram relatados. CONCLUSÃO: O tratamento de curto prazo, em esquema quádruplo com a furazolidona , é bem tolerado, barato e eficaz no re-tratamento do H. pylori. Uma boa opção de re-tratamento para países em desenvolvimento.

The impact of Helicobacter pylori resistance on the efficacy of a short course pantoprazole based triple therapy

BACKGROUND: Many of the currently used Helicobacter pylori eradication regimens fail to cure the infection due to either antimicrobial resistance or poor patient compliance. Those patients will remain at risk of developing potentially severe complications of peptic ulcer disease. AIM: We studied the impact of the antimicrobial resistance on the efficacy of a short course pantoprazole based triple therapy in a single-center pilot study. METHODS: Forty previously untreated adult patients (age range 20 to 75 years, 14 males) infected with Helicobacter pylori and with inactive or healing duodenal ulcer disease were assigned in this open cohort study to 1 week twice daily treatment with pantoprazole 40 mg, plus clarithromycin 250 mg and metronidazole 400 mg. Helicobacter pylori was assessed at entry and 50 ± 3 days after the end of treatment by rapid urease test, culture and histology of gastric biopsies. The criteria for eradication was a negative result in the tests. Susceptibility of Helicobacter pylori to clarithromycin and metronidazole was determined before treatment with the disk diffusion test. RESULTS: One week treatment and follow up were complete in all patients. Eradication of Helicobacter pylori was achieved in 35/40 patients (87.5 percent) and was higher in patients with nitroimidazole-susceptible strains [susceptible: 20/20 (100 percent), resistant: 10/15 (67 percent)]. There were six (15 percent) mild adverse events reports. CONCLUSIONS: A short course of pantoprazole-based triple therapy is well tolerated and effective in eradicating Helicobacter pylori. The baseline metronidazole resistance may be a significant limiting factor in treatment success.

Therapeutic efficacy of ranitidine bismuth citrate with clarithromycin for seven days in the eradication of Helicobacter pylori in Brazilian peptic ulcer patients

CONTEXT: The curative treatment of peptic ulcer is made available nowadays through the eradication of the bacterium Helicobacter pylori, which is associated with it, but the best therapeutic regimen is yet to be determined. OBJECTIVE: To assess the efficacy of a therapeutic regimen with 400 mg ranitidine bismuth citrate associated with 500 mg clarithromycin given twice a day for seven days in a cohort of Brazilian patients with peptic ulcer. TYPE OF STUDY: Cross-sectional study. SETTING: Tertiary-care hospital. PATIENTS: One hundred and twenty nine outpatients, with active or healed peptic ulcers infected by Helicobacter pylori, diagnosed via endoscopy with confirmation via the urease test and histological examination, who had never undergone a regimen for the eradication of the bacterium. PROCEDURE: Administration of 400 mg ranitidine-bismuth and 500 mg clarithromycin twice a day, for seven days. MAIN MEASUREMENTS: Efficacy of the treatment, with a check on the cure done via another endoscopy eight weeks after drug administration. The eradication of the bacterium was determined via the urease test and histological examination. Patients who were negative for both were considered to be cured. RESULTS: Eight patients failed to complete the study. The eradication rate according to intention to treat was 81 percent (104/129) and per protocol was 86 percent (104/121). CONCLUSION: The bismuth ranitidine compound associated with clarithromycin used for one week was shown to be a simple, effective and well-tolerated therapeutic regimen for the eradication of Helicobacter pylori

Omeprazole, Furazolidone, and Tetracycline: an eradication treatment for resistant H. pylori in Brazilian patients with peptic ulcer disease

OBJECTIVES: To determine the efficacy of a simple, short-term and low-cost eradication treatment for Helicobacter pylori (H. pylori) using omeprazole, tetracycline, and furazolidone in a Brazilian peptic ulcer population, divided into 2 subgroups: untreated and previously treated for the infection. PATIENTS AND METHODS: Patients with peptic ulcer disease diagnosed by endoscopic examination and infected by H. pylori diagnosed by the rapid urease test (RUT) and histological examination, untreated and previously unsuccessfully treated by macrolides and nitroimidazole, were medicated with omeprazole 20 mg daily dose and tetracycline 500 mg and furazolidone 200 mg given 3 times a day for 7 days. Another endoscopy or a breath test was performed 12 weeks after the end of treatment. Patients were considered cured of the infection if a RUT and histologic examination proved negative or a breath test was negative for the bacterium. RESULTS: Sixty-four patients were included in the study. The women were the predominant sex (58 percent); the mean age was 46 years. Thirty-three percent of the patients were tobacco users, and duodenal ulcer was identified in 80 percent of patients. For the 59 patients that underwent follow-up examinations, eradication was verified in 44 (75 percent). The eradication rate for the intention-to-treat group was 69 percent. The incidence of severe adverse effects was 15 percent. CONCLUSION: The treatment provides good efficacy for H. pylori eradication in patients who were previously treated without success, but it causes severe adverse effects that prevented adequate use of the medications in 15 percent of the patients

Low efficacy of an ultra-short term, once-daily dose triple therapy with omeprazole, azithromycin, and secnidazole for Helicobacter pylori eradication in peptic ulcer

PURPOSE: To determine the eradication rate of an ultra-short treatment schedule for Helicobacter pylori infection in a population with peptic ulcers, using omeprazole, secnidazole, and azithromycin in a once-daily dose for 3 days. METHODS: Thirty patients with peptic ulcer diagnosed by upper endoscopy and for Helicobacter pylori infection by rapid urease test and histologic examination received omeprazole 40 mg, secnidazole 1000 mg, and azithromycin 500 mg, administered once daily for 3 days. A follow-up exam was performed 12 weeks after the end of the treatment. Patients who were negative for Helicobacter pylori infection by rapid urease test and histologic examination were considered cured. RESULTS: Patients were predominantly female, and the mean age was 50 years. Duodenal peptic ulcer was found in 73 percent of the patients. Eradication was achieved in 9 of the 28 (32 percent) patients as determined from the follow-up endoscopic exam. The eradication rate by intention to treat was 30 percent. Side effects were present in 3 percent of the patients, and compliance to treatment was total. CONCLUSIONS: In spite of the low rate of side effects and good compliance, the eradication index was low. A possible drawback of this therapy is that it reduces the efficacy of macrolide and nitroimidazole compounds in subsequent treatments

Factors affecting Helicobacter pylori eradication using a seven-day triple therapy with a proton pump inhibitor, tinidazole and clarithromycin, in brazilian patients with peptic ulcer

Triple therapy is accepted as the treatment of choice for H. pylori eradication. In industrialized countries, a proton pump inhibitor plus clarithromycin and amoxicillin or nitroimidazole have shown the best results. Our aims were: 1. To study the eradication rate of the association of a proton pump inhibitor plus tinidazole and clarithromycin on H. pylori infection in our population. 2. To determine if previous treatments, gender, age, tobacco, alcohol use, and non-steroidal anti-inflammatory drugs (NSAIDs) change the response to therapy. METHODS: Two hundred patients with peptic ulcer (upper endoscopy) and H. pylori infection (histology and rapid urease test - RUT) were included. A proton pump inhibitor (lansoprazole 30 mg or omeprazole 20 mg), tinidazole 500 mg, and clarithromycin 250 mg were dispensed twice a day for a seven-day period. Eradication was assessed after 10 to 12 weeks of treatment through histology and RUT. RESULTS: The eradication rate of H. pylori per protocol was 65 percent (128/196 patients). This rate was 53 percent for previously treated patients, rising to 76 percent for not previously treated patients, with a statistical difference p<0.01. No significant difference was observed regarding sex, tobacco use, alcohol consumption, and NSAID use, but for elderly patients the difference was p = 0.05. Adherence to treatment was good, and side effects were mild. CONCLUSIONS: A proton pump inhibitor, tinidazole, and clarithromycin bid for seven days resulted in H. pylori eradication in 65 percent of the patients. Previous treatments were the main cause of treatment failure

Validation of 14-C-urea breath test for diagnosis of Helicobacter pylori

The aim of this study was to validate the 14C-urea breath test for use in diagnosis of Helicobacter pylori infection. Thirty H. pylori positive patients, based on histologic test and thirty H. pylori negative patients by histology and anti-H. pylori IgG entered the study. Fasting patients drank 5 uCi of 14C-urea in 20 ml of water. Breath samples were collected at 0, 5, 10, 15, 20 and 30 min. The difference of cpm values between the two groups was significant at all the time intervals, besides time 0 (p<0.0001). At 20 min, the test gave 100 percent sensitivity and specificity with a cut-off value of 562 cpm. Females were higher expirers than males (p=0.005). 14C-urea breath test is highly accurate for Helicobacter pylori diagnosis. It is fast, simple and should be the non-invasive test used after treating Helicobacter pylori infection.