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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.
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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
INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.
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Infecções por Helicobacter , Helicobacter pylori , Adulto , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Metronidazol/uso terapêutico , Claritromicina/uso terapêutico , Levofloxacino/uso terapêutico , Bismuto/uso terapêutico , Amoxicilina/uso terapêutico , Tinidazol , Estudos Prospectivos , Quimioterapia Combinada , Antibacterianos/uso terapêutico , Resistência Microbiana a MedicamentosRESUMO
The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p < 0.05). The overall second-line mITT treatment effectiveness was 84% in both groups. The effectiveness of the most frequent first- and second-line triple therapies was suboptimal (< 90%) in both groups. Optimal efficacy (≥ 90%) was achieved by using bismuth and non-bismuth-based quadruple therapies. In conclusion, the approach to the diagnostics and treatment of H. pylori infection did not generally differ between younger and older patients. Main differences were reported in the concurrent medications, allergy to penicillin and adverse events both in first- and second-line treatment. Optimal effectiveness rates were mostly achieved by using bismuth and non-bismuth-based quadruple therapies. No clinically relevant differences in the effectiveness between the age groups were observed.
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Infecções por Helicobacter , Helicobacter pylori , Hipersensibilidade , Humanos , Idoso , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Antibacterianos/efeitos adversos , Bismuto/uso terapêutico , Quimioterapia Combinada , Inibidores da Bomba de Prótons/efeitos adversos , Penicilinas/uso terapêutico , Resultado do Tratamento , Hipersensibilidade/tratamento farmacológicoRESUMO
BACKGROUND AND AIMS: Several methods are available to diagnose Helicobacter pylori infection. Our objective was to evaluate the tests used for both the initial diagnosis and the confirmation of eradication after treatment in Europe. METHODS: The European Registry on the management of Helicobacter pylori infection is an international, multicentre, prospective, non-interventional registry aiming to evaluate the management of Helicobacter pylori-infected patients in Europe. Countries with at least 100 cases registered from June 2013 to April 2021, and with a validated diagnostic method were analysed. Data were quality reviewed. RESULTS: A total of 34,920 adult patients from 20 countries were included (mean age 51 years; 61% women). To establish the initial diagnosis, invasive tests were performed in 19,801 (71%) patients, non-invasive in 11,369 (41%), and both in 3437 (12%). The most frequent were histology (n = 11,885; 43%), a rapid urease test (n = 10,636; 38%) and an urea breath test (n = 7577; 27%). According to the age, invasive tests were indicated in 11,179 (77%) ≥50 years, and in 8603 (65%) <50 years. Depending on the country, the use of invasive tests ranged from 29-99% in <50 years to 60-99% in ≥50. Most of the tests used to confirm eradication were non-invasive (n = 32,540; 93%), with the urea breath test being the most frequent (n = 32,540; 78%). In 2983 (9%) post-treatment tests, histology (n = 1887; 5%) or a rapid urease test (n = 1223; 4%) were performed. CONCLUSION: A great heterogeneity was observed for the initial diagnosis and confirmation of the eradication. The reasons for the apparent lack of adherence to the clinical guidelines should be further explored.
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Although discovered 40 years ago, Helicobacter pylori infection is still raising diagnostic and therapeutic problems today. The infection is currently managed based on statements in several guidelines, but implementing them in practice is a long process. Increasing antibiotic resistance and weak compliance of the patients limit the efficacy of eradication regimens, leaving much room for improvement. Third-generation proton pump inhibitors have added little to the results of the first two generations. Potassium-competitive acid blockers have a stronger and longer inhibitory action of acid secretion, increasing the intragastric pH. They obtained superior results in eradication when compared to proton pump inhibitors. Instead of innovative antibiotics, derivatives of existing antimicrobials were developed; some new fluoroquinolones and nitazoxanide seem promising in practice, but they are not recommended by the guidelines. Carbonic anhydrase inhibitors have both anti-secretory and bactericidal effects, and some researchers are expecting their revival in the treatment of infection. Capsules containing components of the eradication regimens have obtained excellent results, but are of limited availability. Probiotics, if containing bacteria with anti-Helicobacter pylori activity, may be useful, increasing the rates of eradication and lowering the prevalence and severity of the side effects.
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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
Összefoglaló. A Helicobacter pylori továbbra is a világ legelterjedtebb fertozése: prevalenciája a fejlodo országokban 70-80%, a fejlett országokban csökkeno tendenciát mutat. A dél-magyarországi véradókban a prevalencia 32%-ra csökkent. A migráció a befogadó ország számára a fertozés fokozott kockázatával jár. A szövettani diagnózisban az immunhisztokémiai vizsgálat pontosabb a hagyományos Giemsa-festésnél. A mesterséges intelligencia érzékenysége a hagyományos endoszkópiáéval összehasonlítva 87%, pontossága 86%. Az újgenerációs szekvenálással lehetséges egy biopsziás mintából több antibiotikumérzékenység meghatározása. A Helicobacter pylori kezelésének európai regisztere kimutatta, hogy 2013 és 2018 között a bizmutalapú négyes vagy a 14 napos egyideju négyes kezelések hatásosabbak, mint a hagyományos hármas kezelés, de elterjedésük igen lassú folyamat, jelentos földrajzi különbségekkel. Az új típusú koronavírus (SARS-CoV-2) felléphet Helicobacter pylori fertozésben is, egymás kóros hatását felerosítve. A diagnosztikai módszerek korlátozottak. Protonpumpagátlók szedése növeli a COVID-19-fertozés kockázatát és annak súlyos kimenetelét. Elozetesen ismert peptikus fekély, vérzés, illetve antikoguláns kezelés elott az eradikáció a vírusos fertozés lezajlása után indokolt. A probiotikumoknak az eradikációra gyakorolt hatásáról 20, közepes minoségu metaanalízis született, így a konszenzusokban foglalt álláspontok sem egyértelmuek: a jövoben ezt tisztázni kell. Orv Hetil. 2021; 162(32): 1275-1282. Summary. Helicobacter pylori is still the most widespread infection in the world: its overall prevalence is 70-80% in developing regions, but fortunately it is decreasing in the Western world. The prevalence in blood donors from South-Eastern Hungary decreased from 63% in the 1990's to 32% in 2019. Migration constitutes an increased risk of infection for the destination countries. Immunohistochemistry has proven to be more accurate in histological diagnosis than the conventional Giemsa stain. The sensitivity and accuracy of artificial intelligence as compared to videoendoscopy were 87% and 86%, respectively. The European Register on the management of Helicobacter pylori infection revealed that concomitant quadruple and 14-day bismuth-based therapies are more efficient than triple combinations, although their incorporation in practice is a long-lasting process, with large geographical variations. The novel type of coronavirus (SARS-CoV-2) can also occur in Helicobacter pylori-infected patients, mutually enhancing their pathogenetic effects. Diagnostic possibilities are limited in this setting. The use of proton pump inhibitors increases the risk of viral infection and the severity of the disease. Eradication treatment seems justified in patients with previously known peptic ulcers or gastrointestinal bleeding, or before starting anticoagulant treatment, but must be postponed after resolution of viral infection. The effect of probiotics on eradication was addressed by 20, medium-to-low quality meta-analyses and so, the recommendations of the guidelines are equivocal, which must be clarified in the future with higher quality studies. Orv Hetil. 2021; 162(32): 1275-1282.
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COVID-19 , Infecções por Helicobacter , Helicobacter pylori , Inteligência Artificial , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , SARS-CoV-2RESUMO
The global rise in clarithromycin (Cla) resistance is considered to be the main contributor of Helicobacter pylori (Hp) eradication failures. In nearly half of the Cla-resistant Hp infections, Cla-susceptible bacteria are simultaneously present with the Cla-resistant ones (Cla-heteroresistance). The proportion of resistant bacteria in the bacterial population (R-fraction) and its predictive role for the use of Cla-based therapies in Cla-heteroresistant infections has not yet been investigated. Our retrospective study analyzed gastric biopsy samples of 62 Hp-positive patients with Cla-heteroresistant infection. Fluorescence In Situ Hybridization technique was used to visualize the coexistence of resistant and susceptible bacteria within one tissue sample. R-fraction was quantified on multichannel microimages by digital morphometry. Resistant bacteria had a patchy distribution within the whole bacterial population causing high diversity among the investigated areas. Patients were subdivided into two major groups according to whether a Cla-based eradication attempt was conducted before or after the biopsy sampling. R-fraction was significantly lower among cases having only one previous Cla-based eradication attempt vs. those that had multiple previous eradications, including at least one Cla-containing therapy (0.41 vs. 0.89, p = 0.0308). Majority of the patients without previous eradication attempt had successful eradication with Cla-containing regimen (59.26%), verified by a negative 13C-urea breath test or control biopsy. Multivariable model indicated that the therapeutic outcome using Cla-based regimens depended on the bacterial density rather than the R-fraction. Our study raises the potential use of Cla-containing eradication therapies in certain Cla-heteroresistant Hp infections, taking into account the possible predictive role of bacterial density.
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Antibacterianos/farmacologia , Carga Bacteriana , Claritromicina/farmacologia , Farmacorresistência Bacteriana , Infecções por Helicobacter/microbiologia , Helicobacter pylori/crescimento & desenvolvimento , Estudos Transversais , Feminino , Seguimentos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/patologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the "European Registry on Helicobacter pylori management." METHODS: Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control. RESULTS: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies. DISCUSSION: Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance.
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Antibacterianos/efeitos adversos , Bismuto/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Infecções por Helicobacter/tratamento farmacológico , Inibidores da Bomba de Prótons/efeitos adversos , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Quimioterapia Combinada , Europa (Continente)/epidemiologia , Feminino , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/uso terapêutico , Sistema de RegistrosRESUMO
Clarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection, and thus resistance to this antibiotic is a major cause of treatment failure. Here, we present the results of a retrospective observational study of clarithromycin resistance (Cla-res) in 4744 H. pylori-infected patients from Central Hungary. We use immunohistochemistry and fluorescence in situ hybridization on fixed gastric tissue samples to determine H. pylori infection and to infer Cla-res status, respectively. We correlate this information with macrolide dispensing data for the same patients (available through a prescription database) and develop a mathematical model of the population dynamics of Cla-res H. pylori infections. Cla-res is found in 5.5% of macrolide-naive patients (primary Cla-res), with no significant sex difference. The model predicts that this primary Cla-res originates from transmission of resistant bacteria in 98.7% of cases, and derives from spontaneous mutations in the other 1.3%. We find an age-dependent preponderance of female patients among secondary (macrolide-exposed) clarithromycin-resistant infections, predominantly associated with prior use of macrolides for non-eradication purposes. Our results shed light into the sources of primary resistant cases, and indicate that the growth rate of Cla-res prevalence would likely decrease if macrolides were no longer used for purposes other than H. pylori eradication.
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Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Adulto , Fatores Etários , Idoso , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/transmissão , Helicobacter pylori/isolamento & purificação , Humanos , Hungria/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Modelos Biológicos , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
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 RegistrosAssuntos
Dermatologia , Gastroenterologia , Venereologia , História do Século XIX , História do Século XX , HumanosRESUMO
Helicobacter pylori is the most prevalent infection worldwide, while non-alcoholic fatty liver disease emerged as the most frequent liver disease. The common occurrence can be either by chance or due to certain pathogenetic factors. Epidemiologic studies revealed that the risk of non-alcoholic liver disease is increased in patients infected with Helicobacter pylori. DNA fragments of Helicobacter pylori were rarely identified in human samples of liver carcinoma and fatty liver. Helicobacter pylori could influence the development of non-alcoholic fatty liver either by hormonal (ghrelin? gastrin? insulin?), or by effect of pro-inflammatory cytokines (interleukin 1 and 8, tumor necrosis factor É, interferon É£) and by changes of gut microbiome as well. Probiotic supplementation could improve some clinical parameters of non-alcoholic fatty liver disease and eradication rates of Helicobacter pylori. Regimens used for eradication can be safely administered, although non-alcoholic fatty liver increases the risk of drug-induced liver damage. Controlled studies of the effect of eradication on the development and progression of non-alcoholic fatty liver are warranted.
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Infecções por Helicobacter/complicações , Helicobacter pylori , Hepatopatia Gordurosa não Alcoólica/complicações , Infecções por Helicobacter/fisiopatologia , Humanos , Hepatopatia Gordurosa não Alcoólica/fisiopatologiaRESUMO
BACKGROUND: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended. AIM: To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg). METHODS: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019. RESULTS: One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera® ; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases. CONCLUSION: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results.
Assuntos
Hipersensibilidade a Drogas , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Penicilinas/efeitos adversos , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Claritromicina/uso terapêutico , Helicobacter pylori/efeitos dos fármacos , Humanos , Levofloxacino/uso terapêutico , Metronidazol/uso terapêutico , Penicilinas/uso terapêutico , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Sistema de Registros/estatística & dados numéricos , Tetraciclina/uso terapêuticoRESUMO
BACKGROUND: Clarithromycin (Cla) heteroresistance of Helicobacter pylori (H pylori) infections is commonly assessed by comparing the resistance status of antrum and corpus biopsy samples and by demonstrating the discrepancy between them (interniche heteroresistance). However, fluorescence in situ hybridization (FISH) technique is capable of showing the synchronous presence of susceptible and resistant bacteria (intraniche heteroresistance), enabling the detection of heteroresistant H pylori populations within one biopsy sample. MATERIALS AND METHODS: Antrum and corpus biopsy specimens of 305 H pylori-infected patients were investigated with an rRNA-targeted Cla-resistance FISH test. Anamnestic data were collected from the institutional electronic register. Prevalence rates of susceptible, homo- and heteroresistant cases were correlated with the anamnestic and clinicopathological data. RESULTS: Overall Cla-resistance rate was 23.9% (73 cases), consisting of 35 (11.5%) homoresistant and 38 (12.5%) heteroresistant cases. Thirty-five patients had at least one biopsy site where susceptible and resistant bacteria were present simultaneously. From this subset, 20 cases demonstrated intraniche heteroresistance on both sites. Prior Cla-based eradication attempts were more frequent in homoresistant than in susceptible and heteroresistant cases (P < .001, P < .001, respectively). Cla-containing therapy eradicated heteroresistant infections at a significantly lower rate in comparison with susceptible cases (P = .0112), but more effectively than homoresistants (P = .0393). CONCLUSIONS: The most frequent type of Cla-heteroresistance is the coexistence of susceptible and resistant H pylori bacteria in the same location (intraniche heteroresistance). A previous Cla-based eradication attempt predisposes patients to homoresistant infection. Heteroresistance is characterized by a non-eradication-related background and intermediate characteristics in many respects when compared to susceptible and homoresistant cases.
Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Adulto , Idoso , Biópsia , Farmacorresistência Bacteriana , Feminino , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-IdadeRESUMO
Introduction: The Pan-European Registry on Helicobacter pylori management was conceived in 2013 to monitor eradication practices in Europe for 10 years. Aim: To assess the efficacy of different eradication regimens in a single outpatient clinic of gastroenterology. Method: Between 2013 and 2019, 247 patients were registered in a prospective non-interventional study. The infection was diagnosed either by endoscopy, histology, rapid urease test or 13C-urea breath test. As first-line treatment, the patients received either a 7-day triple regimen (any of PPI + amoxicillin + clarithromycin or tinidazole), 10-day modified sequential treatment (PPI + amoxicillin for 5 days + tinidazole and levofloxacin for 5 days), 10-day quadruple concomitant treatment (PPI + amoxicillin + tetracycline or doxycycline + metronidazole or tinidazole) or bismuth-based quadruple treatment. Bismuth or non-bismuth based quadruple or alternative regimens were given as second- or third-line treatment. Results: The eradication rates on per protocol basis were: 82.7% (95% confidence interval: 68.1-97.4) (first-line regimens), 85.2% (75.4-94.9) (sequential treatment), 95.1% (89.6-100) (concomitant treatment) and 82.6% (69.7-95.9) (bismuth-based quadruple regimen). Second-line regimens achieved 65.2% (48.2-83.0) and third-line therapy 54.5% (19.4-86.6), respectively. Conclusion: The first-line concomitant regimen was superior to triple and not significantly better than the sequential or bismuth-based treatment. Second- and third-line regimens achieved largely suboptimal results. Orv Hetil. 2019; 160(47): 1856-1863.