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GOALS: To perform a systematic review and meta-analysis of endoscopic studies to evaluate an association between diverticulosis and neoplastic lesions in the colon. BACKGROUND: Some epidemiological observations suggest an association between diverticulosis and adenoma/cancer in the colon. However, an increased risk of colon neoplastic lesions in diverticulosis subjects was found to be increased in some studies, but not in others, puzzling data interpretation. STUDY: From the retrieved studies, prevalence of adenomas, advanced adenomas, cancer or neoplasia (advanced adenoma or cancer) was compared between subjects with or without diverticulosis, and comparisons in subgroups were also performed. RESULTS: Data of 26 studies with a total of 419,623 patients were eventually considered, including 27,092 patients with diverticulosis. Data analysis found a statistically significant association between diverticulosis and adenomas (OR: 1.88; 95% CI: 1.50-2.25), advanced adenomas (OR: 1.49; 95% CI: 1.02-2.16), and neoplasia (OR: 1.50; 95% CI: 1.11-2.02), but not with cancer alone (OR: 1.01; 95% CI: 0.70-1.47). These associations were confirmed in the subgroup analyses, by considering Caucasian and Asian populations, prospective and retrospective studies, screening or symptoms settings, and between good or fair quality studies. CONCLUSIONS: A statistically significant association between diverticulosis and adenomas, advanced adenomas and neoplasia, but not with cancer alone was found. However, the strength of association seems to be insufficient to impact on clinical practice.
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Adenoma , Neoplasias do Colo , Colonoscopia , Humanos , Adenoma/patologia , Adenoma/epidemiologia , Neoplasias do Colo/patologia , Neoplasias do Colo/epidemiologia , Prevalência , Diverticulose Cólica/epidemiologia , Diverticulose Cólica/complicações , Diverticulose Cólica/diagnóstico , Fatores de RiscoRESUMO
BACKGROUND AND AIM: Helicobacter pylori infection is one of the most common bacterial infections affecting humans, causing gastroduodenal and extraintestinal diseases. Treatment of the infection remains challenging for the clinicians, and different factors are involved in the failure of the therapeutic approach. The importance of the intensity of acid secretion inhibition remains an unclear issue. The aim of this study is to assess whether 80 mg/day esomeprazole-based 10-day sequential therapy (esomeprazole-ST) achieved different eradication rates when compared to 80 mg/day pantoprazole-based analogous regimen (pantoprazole-ST). METHODS: This was a retrospective observational study where data of consecutive patients referred by their physicians to our unit to perform an upper gastrointestinal endoscopy were analyzed. RESULTS: Overall, 1,327 patients were available for the analysis: 599 and 728 patients received pantoprazole-ST and esomeprazole-ST, respectively. Eradication rate was significantly higher in patients receiving esomeprazole-ST (92.6%, 95% CI: 91-94.5) than pantoprazole-ST (89.3%, 95% CI: 86.7-91.7; difference: 3.3%; 95% CI: 0.2-6.5; P = 0.037). Even after a multivariate analysis, the esomeprazole-ST achieved a significantly higher eradiation (OR: 1.44; 95% CI: 1.1-2.17). CONCLUSIONS: This study showed that esomeprazole-ST achieved significantly higher H. pylori cure rates than pantoprazole-ST. Prospective and well-designed trials are demander to confirm this prelaminar finding.
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OBJECTIVE: To evaluate the use, effectiveness and safety of Helicobacter pylori empirical rescue therapy in third and subsequent treatment lines in Europe. DESIGN: International, prospective, non-interventional registry of the clinical practice of European gastroenterologists. Data were collected and quality reviewed until October 2021 at Asociación Española de Gastroenterología-Research Electronic Data Capture. All cases with three or more empirical eradication attempts were assessed for effectiveness by modified intention-to-treat and per-protocol analysis. RESULTS: Overall, 2144 treatments were included: 1519, 439, 145 and 41 cases from third, fourth, fifth and sixth treatment lines, respectively. Sixty different therapies were used; the 15 most frequently prescribed encompassed >90% of cases. Overall effectiveness remained <90% in all therapies. Optimised treatments achieved a higher eradication rate than non-optimised (78% vs 67%, p<0.0001). From 2017 to 2021, only 44% of treatments other than 10-day single-capsule therapy used high proton-pump inhibitor doses and lasted ≥14 days. Quadruple therapy containing metronidazole, tetracycline and bismuth achieved optimal eradication rates only when prescribed as third-line treatment, either as 10-day single-capsule therapy (87%) or as 14-day traditional therapy with tetracycline hydrochloride (95%). Triple amoxicillin-levofloxacin therapy achieved 90% effectiveness in Eastern Europe only or when optimised. The overall incidence of adverse events was 31%. CONCLUSION: Empirical rescue treatment in third and subsequent lines achieved suboptimal effectiveness in most European regions. Only quadruple bismuth-metronidazole-tetracycline (10-day single-capsule or 14-day traditional scheme) and triple amoxicillin-levofloxacin therapies reached acceptable outcomes in some settings. Compliance with empirical therapy optimisation principles is still poor 5 years after clinical practice guidelines update. TRIAL REGISTRATION NUMBER: NCT02328131.
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BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.
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Infecções por Helicobacter , Helicobacter pylori , Quinolonas , Adulto , Amoxicilina , Antibacterianos/uso terapêutico , Bismuto , Claritromicina/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Humanos , Levofloxacino , Moxifloxacina/uso terapêutico , Penicilinas/efeitos adversos , Estudos Prospectivos , Inibidores da Bomba de Prótons , Quinolonas/uso terapêutico , Sistema de Registros , Tetraciclina/uso terapêuticoRESUMO
BACKGROUND: Managing Helicobacter pylori infection requires constant decision making, and each decision is open to possible errors. AIM: The aim was to evaluate common mistakes in the eradication of H. pylori, based on the "European Registry on Helicobacter pylori management". METHODS: European Registry on Helicobacter pylori management is an international multicentre prospective noninterventional registry evaluating the decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice. RESULTS: Countries recruiting more than 1000 patients were included (26,340 patients). The most common mistakes (percentages) were: (1) To use the standard triple therapy where it is ineffective (46%). (2) To prescribe eradication therapy for only 7 to 10 days (69%). (3) To use a low dose of proton pump inhibitors (48%). (4) In patients allergic to penicillin, to prescribe always a triple therapy with clarithromycin and metronidazole (38%). (5) To repeat certain antibiotics after eradication failure (>15%). (6) Failing to consider the importance of compliance with treatment (2%). (7) Not to check the eradication success (6%). Time-trend analyses showed progressive greater compliance with current clinical guidelines. CONCLUSION: The management of H. pylori infection by some European gastroenterologists is heterogeneous, frequently suboptimal and discrepant with current recommendations. Clinical practice is constantly adapting to updated recommendations, although this shift is delayed and slow.
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Infecções por Helicobacter , Helicobacter pylori , Amoxicilina , Antibacterianos , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Humanos , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Estudos Prospectivos , Inibidores da Bomba de Prótons , Sistema de RegistrosRESUMO
OBJECTIVE: The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care. DESIGN: International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed. RESULTS: 30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%-90%). CONCLUSION: Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.
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Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Padrões de Prática Médica/estatística & dados numéricos , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de RegistrosRESUMO
MATERIALS AND METHODS: Consecutive foreigner patients with H. pylori infection following at least one therapy failure were enrolled. All patients underwent upper endoscopy with gastric biopsies used for both histologic examination and culture/susceptibility test. Rescue therapies administered accordingly to susceptibility testing were rifabutin-based therapy, levofloxacin-based therapy, sequential. Pylera was prescribed regardless the resistance pattern. RESULTS: A total of 103 (M/F: 27/76, mean age: 41.9 y, range: 18 to 85) were enrolled. The overall resistance rates toward clarithromycin, metronidazole, and levofloxacin were 76.7%, 66%, and 42.7%, respectively, with triple resistance present in 33.9% of bacterial isolates. Eradication rates were 71.4% on 40 patients for rifabutin-based therapy, 82.8% on 42 cases for levofloxacin-based therapy, 75% on 11 patients treated with sequential therapy, and 100% on 10 cases who received Pylera regimen. CONCLUSIONS: To our knowledge, this is the first study assessing H. pylori eradication rates in foreigner patients, who failed at least one therapeutic attempt, managed in Italy. Even by using a culture-based approach, the infection was not cured in a definite number of patients.
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Infecções por Helicobacter , Helicobacter pylori , Adulto , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , HumanosRESUMO
OBJECTIVES: Antimicrobial resistance to clarithromycin and metronidazole significantly affects the cure rate of standard therapies for Helicobacter pylori infection. We tested whether different MIC levels of resistance to these antibiotics play a role in therapeutic efficacy. METHODS: This was a post hoc analysis of data from a therapeutic trial in which patients with antibiotic susceptibility testing (Etest) received first-line sequential therapy. The level of antibiotic resistance was classified according to MIC values into low (MIC from >0.5 to ≤8 for clarithromycin, and from >8 to ≤32 for metronidazole) and high (MIC from >8 to 256 mg/L for clarithromycin, and from >32 to 256 mg/L for metronidazole). RESULTS: Data from 1006 patients were included. There were 520 (51.7%) patients with susceptible strains, 136 (13.5%) with clarithromycin-resistant strains, 144 (14.3%) with metronidazole-resistant strains and 206 (20.5%) with clarithromycin-resistant and metronidazole-resistant strains. In the presence of double resistance, the cure rate was still high (38/41, 92.7%) when MIC levels were low and it was reduced (94/112, 83.9%) only when MIC levels of both antibiotics were high. The cure rates did not significantly differ between patients with single antibiotic-resistant strains, irrespective of MIC values, and those with susceptible strains. CONCLUSIONS: We found that MIC levels of resistance to either clarithromycin or metronidazole play a role in H. pylori therapy outcome and that bacterial resistance becomes relevant in vivo when clarithromycin-resistant and metronidazole-resistant strains have high MIC values for at least one of these antibiotics.
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Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Metronidazol/uso terapêutico , Adulto , Idoso , Antibacterianos/farmacologia , Claritromicina/farmacologia , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
INTRODUCTION: Eradicating Helicobacter pylori continues to be a challenge, and no treatment regimen is uniformly successful in all treated patients. Triple therapy with rifabutin and amoxicillin is a successful rescue therapy after consecutive treatment failures. We designed this study to test the efficacy of 12-day rifabutin-based triple therapy in patients infected with multidrug-resistant strains. METHODS: Consecutive patients with dyspeptic symptoms after at least 1 antibiotic therapy course for H. pylori infection harboring triple-resistant (clarithromycin, metronidazole, levofloxacin) strains were enrolled. They received triple therapy with esomeprazole 40 mg bid, amoxicillin 1 g bid, and rifabutin 150 mg od for 12 days. Patients who failed rifabutin therapy were treated empirically on the basis of the judgment of the treating physician. RESULTS: A total of 254 out of 756 tested patients were found to be infected with a triple-resistant H. pylori strains after at least 1 antibiotic therapy course. Overall, the infection was eradicated in 213 patients, corresponding to a cure rate of 82.9% (95% CI, 78.3-87.5) by intention-to-treat analysis and 88.7% (95% CI, 84.7-92.7) at per-protocol analysis. In multivariate analysis, no factor was identified as an independent predictor of bacterial eradication. CONCLUSIONS: There is no current standard for the growing population of patients with multidrug-resistant strains of H. pylori. The 12-day low-dose rifabutin/high-dose proton pump inhibitor regimen is a safe and reliable option for patients infected with triple-resistant strains.
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Amoxicilina/administração & dosagem , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Rifabutina/administração & dosagem , Adulto , Idoso , Antibacterianos/administração & dosagem , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana Múltipla , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Inibidores da Bomba de Prótons/administração & dosagem , Resultado do TratamentoRESUMO
PURPOSE: Bacterial resistance toward the most used antibiotics is increasing in Helicobacter pylori strains worldwide. Emergence of multidrug resistance significantly affects the efficacy of standard therapy regimens. Therefore, monitoring for primary antimicrobial resistance is essential for H. pylori management in clinical practice. METHODOLOGY: H. pylori isolates obtained from patients consecutively observed in a single center were tested for primary resistance by using E-test method. Bacterial strains showing MIC values >0.5, >8 and >1 mg/L toward clarithromycin, metronidazole and levofloxacin, respectively, were considered resistant. The trend of antibiotic prevalence, either single or combined, during 2010-2016 was assessed. RESULTS: Antibiotic susceptibility data were available in 1424 (82.3%) out of 1730 tested patients. The overall resistance for all the three antibiotics showed an increasing trend from 2010 to 2013 (clarithromycin: from 19% to 35.6%; metronidazole: from 33.6% to 45.3%; levofloxacin: from 19% to 29.7%; p < .001), when a plateau until 2016 was observed (clarithromycin: 35.9%; metronidazole: 40.2%; levofloxacin: 29.3%). A similar trend occurred for clarithromycin-metronidazole combined resistance rate (2010: 11.4%; 2013: 28.2%; 2016: 21.9%). CONCLUSION: Our data suggest that prevalence of primary resistance in H. pylori isolates toward the most frequently used antibiotics probably reached a plateau in the last years.
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Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Adulto , Claritromicina/uso terapêutico , Feminino , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Itália/epidemiologia , Levofloxacino/uso terapêutico , Masculino , Metronidazol/uso terapêutico , Testes de Sensibilidade Microbiana , Pessoa de Meia-IdadeRESUMO
Clarithromycin-based regimens are commonly used as a first-line therapy for Helicobacter pylori-positive patients; however, resistance to clarithromycin has led to treatment failures. The aim of this study was to evaluate the feasibility of using stool samples to detect the presence of H. pylori DNA while concurrently detecting mutations associated with resistance to clarithromycin. For this purpose, total DNA was extracted from 294 raw stool specimens from H. pylori-positive and -negative patients. TaqMan real-time PCR amplification was used to detect the presence of H. pylori as well as to predict the phenotype of the organism and the related outcome for patients treated with clarithromycin. Clarithromycin resistance was determined upon analysis of the PCR result. Patients were also tested by a urea breath test and were subjected to esophagogastroduodenoscopy, followed by histology, culture, and a rapid urease test, in order to obtain a consensus patient infection status. Of 294 total stool samples, 227 were deemed true positive. The sensitivity of H. pylori detection by PCR was 93.8%. Of 213 true-positive samples that were sequenced, 36.2% showed point mutations associated with clarithromycin resistance (A2142C, A2142G, A2143G). The final correlation of the mutant genotypes as determined by sequencing with the eradication of infection was 86%. We found that Helicobacter pylori DNA can be detected in human stool specimens with high sensitivity and can therefore be used to determine the presence of the bacterium without obtaining a biopsy sample. Moreover, genotypic resistance to clarithromycin can be predicted without obtaining a biopsy sample, facilitating the choice of the right therapeutic approach.
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Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , DNA Bacteriano/análise , DNA Bacteriano/genética , Fezes/microbiologia , Infecções por Helicobacter/microbiologia , Humanos , Técnicas de Diagnóstico Molecular/métodos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Bismuth quadruple therapy (BQT) is the recommended rescue therapy for Helicobacter pylori (H. pylori) infection. This study aimed to assess the efficacy and safety of a 10-day BQT regimen in patients who failed previous therapies and were infected with multiresistant H. pylori strains MATERIALS AND METHODS: Helicobacter pylori-infected patients underwent endoscopy, culture, and susceptibility test for clarithromycin, metronidazole, and levofloxacin. Treatment with three-in-one capsule (Pylera®) four times daily and esomeprazole 20 mg twice daily for 10 days was administered. Treatment-emergent adverse events (TEAEs) were registered. RESULTS: A total of 116 patients with persistent H. pylori infection following at least one eradication therapy attempt were treated. Overall, resistance toward clarithromycin was detected in 80% of strains, toward metronidazole in 70%, and levofloxacin in 47.5%, with dual or triple resistance in 72.5% of cases. An eradication rate of 81.0% (95% CI: 73.0-87.1) and 87.0% (95% CI: 79.4-92.1) at ITT and PP analyses, respectively, was achieved. The cure rate remained high until it was used as fourth-line regimen, while it dropped to low values (<67%) in those patients with more than 4 therapy failures. A total of 65.7% (95% CI: 56.4-74.0) patients complained of TEAEs. CONCLUSIONS: Our data found that bismuth-based quadruple regimen is effective as rescue therapy for curing patients infected with multiresistant H. pylori strains.
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Antibacterianos/administração & dosagem , Bismuto/administração & dosagem , Farmacorresistência Bacteriana , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Terapia de Salvação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Bismuto/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/efeitos adversos , Terapia de Salvação/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
This review summarizes important studies regarding H.pylori therapy published from April 2013 to April 2014. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, predominantly optimized triple therapies and non-bismuth quadruple schemes. Regarding newer non-bismuth quadruple regimens, the compliance and tolerance seem to be similar for sequential and concomitant regimens. Notably, no study yet has demonstrated a clear statistical superiority for either, and a systematic review and meta-analysis may be warranted. Other studies examined the role of levofloxacin and bismuth based therapies in H. pylori eradication. The efficacy of bismuth as a second-line after sequential therapy was particularly noteworthy. Levofloxacin-based therapies also appear to be useful and versatile as part of different antibiotic combinations and in first-, second-, and third-line therapies. The emerging problem of quinolone resistance remains a worry. Individualized therapy, based on factors such as antimicrobial information, resistance data, and CYP2C19 metabolism, may well be the most notable future trend to emerge this year.
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Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Quimioterapia Combinada , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , HumanosRESUMO
BACKGROUND: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. AIM: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). METHODS: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. RESULTS: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. CONCLUSIONS: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.
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Infecções por Helicobacter , Helicobacter pylori , Adulto , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Metronidazol , Claritromicina/uso terapêutico , Levofloxacino/uso terapêutico , Bismuto , Estudos Prospectivos , Quimioterapia Combinada , Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Amoxicilina/uso terapêutico , Tetraciclina , Sistema de RegistrosRESUMO
BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.
Assuntos
Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Adesão à Medicação , Inibidores da Bomba de Prótons , Sistema de Registros , Humanos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Masculino , Adesão à Medicação/estatística & dados numéricos , Feminino , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Europa (Continente) , Adulto , Amoxicilina/uso terapêutico , Amoxicilina/administração & dosagem , Resultado do Tratamento , Claritromicina/uso terapêutico , Idoso , Dispepsia/tratamento farmacológico , Dispepsia/microbiologia , Metronidazol/uso terapêutico , Metronidazol/administração & dosagem , Bismuto/uso terapêutico , Bismuto/administração & dosagem , Bismuto/efeitos adversosRESUMO
BACKGROUND & AIMS: Eradication of Helicobacter pylori using empiric therapy has become difficult as a result of increasing resistance to antibiotics. We evaluated the efficacy of specific treatments, selected based on response of bacterial samples to culture with clarithromycin, levofloxacin, and metronidazole, for patients infected with resistant strains of H pylori. METHODS: We performed a prospective study at a single center of 236 consecutive patients with persistent H pylori infection, despite 1 or more treatment attempts, and documented resistance to at least 1 antimicrobial agent (based on bacterial culture tests). Biopsy samples were collected by endoscopy and cultured in selective media. Patients received either 10 days of levofloxacin (250 mg twice daily for 131 patients with susceptible infections) or 12 days of rifabutin (150 mg once daily for 105 patients resistant to levofloxacin) in combination with amoxicillin (1 g twice daily) and esomeprazole (40 mg twice daily). Efficacy of eradication was determined by the (13)C-urea breath test, 6 to 8 weeks after therapy. Compliance and side effects were determined via personal interviews at the end of therapy. Rifabutin toxicity was monitored by analysis of blood samples. RESULTS: H pylori infection was cured in 118 of the patients who received levofloxacin triple therapy (90%; 95% confidence interval, 85%-95%) and 93 of the patients who received rifabutin triple therapy (88.6%; 95% confidence interval, 82%-95%). In each group, the cure rate did not differ significantly between patients infected with H pylori strains resistant to single or multiple antibiotics. Mild side effects occurred in 15.5% and 14.9% of patients resistant to single or multiple antibiotics, respectively, and self-limiting neutropenia was observed in 1 (0.7%) case. CONCLUSIONS: Selection of triple therapy with either levofloxacin or rifabutin, based on results from bacterial culture tests, cures H pylori infection in about 90% who did not previously respond to antibiotics.
Assuntos
Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Metronidazol/uso terapêutico , Rifabutina/uso terapêutico , Adulto , Idoso , Antibacterianos/farmacologia , Biópsia , Testes Respiratórios , Claritromicina/farmacologia , Quimioterapia Combinada , Feminino , Mucosa Gástrica/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Rifabutina/farmacologia , Resultado do Tratamento , Ureia/análiseRESUMO
The treatment of Helicobacter pylori infection is in a state of flux as traditional therapies fail and new therapies do not achieve the 90% eradication rates desired by clinicians. Triple therapy, which has been the mainstay of treatment in many countries over the last decade, now has suboptimal results in many parts of the world. A number of new treatments have been described with variable success in different parts of the world. In this article, the fundamentals of treatment for H. pylori treatment are reviewed and new treatment algorithms are proposed for regions of the world where triple therapy is failing. Sequential therapy and quadruple therapy (either bismuth-based or non-bismuth-based) are the best current options to replace initial treatment with triple therapy. When initial treatment fails, salvage treatments using rifabutin and levofloxacin are the best options. With knowledge of local resistance patterns and with meticulous confirmation of eradication with retreatment, most H. pylori infections can be successfully eradicated.
Assuntos
Antibacterianos/administração & dosagem , Antiulcerosos/administração & dosagem , Farmacorresistência Bacteriana , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Bismuto/administração & dosagem , Bismuto/uso terapêutico , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Infecções por Helicobacter/microbiologia , Humanos , Rifabutina/administração & dosagem , Rifabutina/uso terapêutico , Resultado do TratamentoRESUMO
AIM: To assess the remission rate of gastric low-grade B-cell mucosa-associated lymphoid tissue lymphoma after an eradication therapy in Helicobacter pylori-negative patients. METHODS: We performed a systematic review with pooled analysis of published studies. Data were analyzed according to: (1) number of H. pylori-negative patients treated with only eradication therapy; (2) number of patients in whom the complete lymphoma remission was achieved; and (3) the method used to exclude H. pylori infection. RESULTS: Overall, 11 studies with 110 patients met the inclusion criteria for this pooled analysis. H. pylori infection was excluded in all studies with at least 3 different diagnostic tests. Eradication therapy achieved a complete lymphoma regression in 17 (15.5%; 95% confidence interval, 8.7-22.2) patients. CONCLUSIONS: Eradication therapy is successful in a small but distinct subgroup of H. pylori-negative patients with low-grade mucosa-associated lymphoid tissue lymphoma. On the basis of the generally indolent behavior of this neoplasia, before resorting to aggressive, costly, and potentially more toxic oncologic therapies, it would seem reasonable to attempt eradication therapy in all patients, irrespective of their H. pylori status.