RESUMO
BACKGROUND: First-line therapy does not always provide a high level of Helicobacter pylori eradication due to the increase of H. pylori resistance to antibiotics; therefore, it remains necessary to identify the most effective rescue treatments. The purpose of this study was to evaluate the efficacy and safety of empirical H. pylori furazolidone-containing regimens. MATERIALS AND METHODS: Adult H. pylori infected patients empirically treated with furazolidone-containing eradication regimens were registered in an international, prospective, multicenter non-intervention European registry on H. pylori management (Hp-EuReg). Data were collected at AEG-REDCap e-CRF from 2013 to 2021 and the quality was reviewed. Modified intention-to-treat (mITT) effectiveness analyses were performed. RESULTS: Overall 106 patients received empirical furazolidone-containing therapy in Russia. Furazolidone was prescribed in a sequential scheme along with amoxicillin, clarithromycin and a proton pump inhibitor in 68 (64%) cases, triple regimens were prescribed in 28 (26%) patients and quadruple regimens in 10 (9.4%). Treatment duration of 7 days was assigned to 2 (1.9%) patients, 10-day eradication therapy in case of 80 (75%) and 14 days - in 24 (23%) patients. Furazolidone was mainly used in first- (79%) and second-line (21%) regimens. The methods used to diagnose H. pylori infection were: histology (81%), stool antigen test (64%), 13C-urea breath test (6.6%), and rapid urease test (1.9%). The mITT effectiveness of sequential therapy was 100%; 93% with the triple therapy and 75.5% with quadruple therapy. Compliance was reported in 98% of cases. Adverse events were revealed in 5.7% of patients, mostly nausea (3.8%). No serious adverse events were reported. CONCLUSION: Furazolidone containing eradication regimens appear to be an effective and safe empirical therapy in Russia.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Adulto , Humanos , Furazolidona/efeitos adversos , Estudos Prospectivos , Quimioterapia Combinada , Antibacterianos/efeitos adversos , Amoxicilina/efeitos adversos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/diagnóstico , Inibidores da Bomba de Prótons/efeitos adversos , Resultado do Tratamento , Federação Russa/epidemiologia , Sistema de RegistrosRESUMO
Continuous evaluation of the actual clinical practice of diagnosis and treatment of Helicobacter pylori is crucial in order to provide the best standard of care and to compare health outcomes with expert recommendations. AIM: to evaluate the effectiveness of the standard triple therapy (amoxicillin, clarithromycin, a proton pump inhibitor) and the standard triple therapy plus bismuth tripotassium dicitrate. MATERIALS AND METHODS: Observational, prospective, multicenter study, carried out in one single Russian centre A.S. Loginov Moscow Clinical Scientific Center as part of the Hp-EuReg. Patients were included from 2013 to November 2019 by Russian gastroenterologists. RESULTS: A total of 647 patients were collected and 330 were administered either standard triple therapy ((amoxicillin, clarithromycin, a proton pump inhibitor) or standard triple therapy plus bismuth tripotassium dicitrate. Invasive methods is dominates in the initial diagnosis of H. pylori: the frequency of use of the quick urease test decreased from 50% in 2013 to 31% in 2019. Serology was used in 27.9%. There has been an increase in the use of the13C-urea breath test from 13% in 2013 to 31% in 2019. The histological method (7.5%) and the stool antigen test (3.2%) were used less frequently. For eradication control non-invasive methods are mostly used:13C-UDT (82.7%) and the stool antigen test (14.4%). The effectiveness of standard triple therapy (mITT) was 68% with a 7-day course, 79% with a 10-day course, and 70% with a 14-day course. Combination of bismuth and standard triple therapy eradicates H. pylori (mITT) in 63%, 75% and 89%, respectively. CONCLUSION: An improvement in the clinical practice of managing patients with H. pylori infections has been noted. The standard triple therapy in combination with bismuth tripotassium dicitrate, prescribed for 14 days, is more effective.
Assuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Claritromicina/uso terapêutico , Quimioterapia Combinada , Humanos , Moscou , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Sistema de Registros , Federação RussaRESUMO
BACKGROUND: As part of an observational multicenter prospective study European Registry on the management of Helicobacter pylori infection, conducted on the initiative of the European H. pylori and Microbiota Study Group, the compliance of clinical practice in the management of patients with Helicobacter pylori infection in Kazan with clinical guidelines was assessed. MATERIALS AND METHODS: The data of 437 patients included into the register by clinical sites in Kazan in 20132019 were analyzed. The methods used for the initial diagnosis of H. pylori infection and eradication control were evaluated. The frequency of various eradication therapy regimens prescription was analyzed in 379 cases. Data regarding the effectiveness of eradication therapy was analyzed in 173 patients. RESULTS: The rapid urease test (44.2% of cases) and cytology/histology (60% of cases) were most often used for the initial diagnosis of H. pylori infection; however non-invasive methods such as 13C-urea breath (9.2%), serology (6.2%), H. pylori stool antigen test (2.3%) were less common. In 21.7% of patients two methods of H. pylori detection were used for primary diagnosis. The control test to evaluate the effectiveness of eradication therapy at the recommended timepoint was performed in 46.2% of patients. 13C-urea breath test (31.7%), stool PCR/stool antigen test (28.7%), rapid urease test (22.3%), cytology/histology (26.2% of cases) prevailed in the assessment of eradication rate. Standard triple therapy, including proton pump inhibitor, clarithromycin and amoxicillin was most commonly prescribed as first-line therapy (64.6% of cases). The duration of eradication therapy was 14 days in the majority of cases with pantoprazole as the most common proton pump inhibitor in standard triple therapy regimens (84.8%). The efficacy of 14-day standard triple therapy (mITT) was 87.0%. CONCLUSION: The results indicate a high frequency of non-invasive methods use for assessing the effectiveness of eradication therapy; however, the overall rate of eradication efficacy assessment is low, limiting the possibility of analyzing the eradication results. The effectiveness of the most common 14-day standard triple first-line therapy in Kazan doesnt reach the recommended 90% eradication level. This could be explained by high rate of pantoprazole use, which is not an optimal proton pump inhibitor in eradication therapy regimens.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Sistema de RegistrosRESUMO
The multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group (EHMSG) is conducted in 27 countries in Europe. The data from the Russian part of the European registry for the management of Helicobacter pylori infection (European Registry on the management of Helicobacter pylori infection, protocol: "Hp-EuReg") allows us to analyze the real clinical practice of diagnosis and treatment of H. pylori and compare it with international recommendations. MATERIALS AND METHODS: A comparative analysis of the data entered in the register by the Russian research centers "Hp-EuReg", in the period from 2013 to 2018, was conducted. RESULTS AND DISCUSSION: Invasive diagnostic methods prevail for the primary diagnosis of H. pylori [histology - 20.3% (in 2013 year) - 43.9% (in 2018 year), rapid urease test - 31.7% and 47.8% respectively]. The most popular mode of eradication therapy is a 10-day triple therapy (62.8-76.2%), the effectiveness of which does not exceed 79% (per protocol). Invasive tests (histology) are the leading method for control the effectiveness of therapy, however, there is a tendency towards a wider use of non-invasive methods (H. pylori stool antigen - from 17% in 2013 to 29.3% in 2018 and urea breath test from 6.9 to 18.3%, respectively). Serological test to control the effectiveness of eradication is still used from 8.2% (2013) to 6.1% (2018). Eradication therapy was not performed in 28% of patients throughout the entire observation period. CONCLUSION: In Russia, despite approved domestic and international recommendations, deviations in clinical practice persist, both during eradication therapy and in monitoring the effectiveness of eradication therapy.
Assuntos
Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Antígenos de Bactérias/análise , Testes Respiratórios/métodos , Quimioterapia Combinada/métodos , Fezes/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Antibacterianos/administração & dosagem , Antiulcerosos/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Europa (Continente) , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/imunologia , Humanos , Estudos Prospectivos , Sistema de Registros , Federação Russa/epidemiologiaRESUMO
AIM: European Registry on the management of Helicobacter pylori infection («Hp-EuReg¼) - a multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group, conducted in 27 European countries in order to evaluate the real clinical practice of diagnosis and treatment of H. pylori and its comparison with international recommendations. MATERIALS AND METHODS: The analysis of 2360 patients entered in the register by the Russian centres of «Hp-EuReg¼ in 2013-2017, who were underwent 1st line eradication therapy. RESULTS: The most common methods of primary diagnosis of H. pylori are histological (37.7%), rapid urease test (29.2%) and serology (29.7%). The duration of eradication therapy in 9.4% of cases was 7 days, in 65.3% - 10 days, and in 25.3% - 14 days. To control the effec- tiveness of treatment, H. pylori antigen in feces (31.3%), urea breath test (23.4%) and histological method (23.3%) were used. In 3.6% cases was used serology by mistake. In 17.3% of patients control was not carried out. The effectiveness of triple therapy with a PPI, amoxicillin, clar- ithromycin (per protocol) was 67.6%, with 7-day course, 81.1% at 10-day and 86.7% at 14-day course. Eradication rate of triple therapy with addition of bismuth (per protocol) reached 90,6% in the group receiving 10-day scheme and 93.6% in the group receiving the 14-day treatment. CONCLUSION: Significant deviations of clinical practice from expert recommendations, most pronounced at the stage of monitoring the effectiveness of therapy, were noted. The suboptimal efficacy of triple therapy is shown.
Assuntos
Antibacterianos , Infecções por Helicobacter , Inibidores da Bomba de Prótons , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Claritromicina , Quimioterapia Combinada , Europa (Continente) , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Humanos , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Sistema de RegistrosRESUMO
Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.
Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Inibidores da Bomba de Prótons/uso terapêutico , Neoplasias Gástricas/diagnóstico , Amoxicilina/uso terapêutico , Bismuto/uso terapêutico , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana , Quimioterapia Combinada , Dispepsia/microbiologia , Detecção Precoce de Câncer , Medicina Baseada em Evidências , Fluoroquinolonas/uso terapêutico , Gastrite/microbiologia , Microbioma Gastrointestinal , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/prevenção & controle , Humanos , Testes de Sensibilidade Microbiana , Nitroimidazóis/uso terapêutico , Guias de Prática Clínica como Assunto , Fatores de Risco , Estômago/microbiologia , Neoplasias Gástricas/microbiologiaRESUMO
Plant derived compounds have played an important role in the development of several clinically useful anticancer drugs. The aim of the present study was 1) to evaluate for the first time the anti-proliferative activity of a polyphenol enriched extract obtained from leaf, fruit and stem of Tunisian variety of Pistacia lentiscus against two cultured cancer cells, and 2) to carry out a phytochemical analysis of vegetable extracts particularly by determining the chemical composition of phenolics (total polyphenols, flavonoids and condensed tannins content in solvents with varying polarities), 3) to evaluate the antioxidant activity and identify the major compounds by RP-HPLC. Leaf extract using methanol/water (8:2) showed the highest polyphenol content (124.1 mg GAE/g DW). Moreover, total antioxidant capacity, reducing power and antiradical capacities against DPPH were maximal in leaf extracts with IC50 significantly lower than that standard (BHT). In MTT assay, methanol (8:2) extract exerted the most potent cytotoxic effect. The leaf extract exhibited an important antiproliferative activity (IC50: 135.67 ± 2.5 and 250.45 ± 1.96 µg/ml in CaCo2 and AGS cells respectively) but the infusion extracts of fruit stems and leaves were inactive. The RP-HPLC analysis revealed the presence of several phenolic compounds in P. lentiscus leaf, fruit and stem including tannic acid, gallic acid, digalloyl quinic acid derivative, quercetin and p-coumaric acid as major phenolics. The high phenolic content and the important antioxidant activities of P. lentiscus extract could be a useful source of natural products and may be increasingly important for human consumption, prevention of damages caused by oxygen free as well as for the agro-food, cosmetic and pharmaceutical industries.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Pistacia/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Células CACO-2 , Linhagem Celular Tumoral , Frutas/química , Humanos , Neoplasias/tratamento farmacológico , Extratos Vegetais/química , Folhas de Planta/química , Caules de Planta/química , Polifenóis/química , TunísiaRESUMO
The role of Campylobacter jejuni as the triggering agent of Guillain-Barré syndrome (GBS) has not been reassessed since the end of the 1990s in France. We report that the number of C. jejuni-related GBS cases increased continuously between 1996 and 2007 in the Paris region (mean annual increment: 7%, P = 0·007).
Assuntos
Infecções por Campylobacter/complicações , Campylobacter jejuni/imunologia , Síndrome de Guillain-Barré/epidemiologia , Adulto , Idoso , Feminino , França , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Paris/epidemiologiaRESUMO
UNLABELLED: This article describes the isolation and characterization of a Campylobacter-like isolate originating from the faeces of a sick leopard tortoise. Molecular as well as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) characterization suggests that it could correspond to a new Campylobacter species. SIGNIFICANCE AND IMPACT OF THE STUDY: The major impact of this work is the demonstration that proteomics and especially MALDI-TOF typing can be used as an alternative method to 16S rDNA sequencing for phylogeny and can lead to the discovery of new Campylobacters.
Assuntos
Campylobacter/classificação , Tipagem Molecular/métodos , Filogenia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Tartarugas/microbiologia , Animais , Campylobacter/genética , Campylobacter/isolamento & purificação , Campylobacter fetus/classificação , DNA Ribossômico/química , Fezes/microbiologia , Masculino , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. METHODS: In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII(®)). RESULTS: By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). CONCLUSIONS: Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.
Assuntos
Adenocarcinoma/etiologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/imunologia , Immunoblotting/métodos , Neoplasias Gástricas/etiologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Adulto , Idoso , Anticorpos Antibacterianos/análise , Anticorpos Antibacterianos/sangue , Cárdia/patologia , Estudos de Casos e Controles , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática/métodos , Europa (Continente)/epidemiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estudos Soroepidemiológicos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologiaRESUMO
Atrophic gastritis, intestinal metaplasia, and epithelial dysplasia of the stomach are common and are associated with an increased risk for gastric cancer. In the absence of guidelines, there is wide disparity in the management of patients with these premalignant conditions. The European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter Study Group (EHSG), the European Society of Pathology (ESP) and the Sociedade Portuguesa de Endoscopia Digestiva (SPED) have therefore combined efforts to develop evidence-based guidelines on the management of patients with precancerous conditions and lesions of the stomach (termed MAPS). A multidisciplinary group of 63 experts from 24 countries developed these recommendations by means of repeat online voting and a meeting in June 2011 in Porto, Portugal. The recommendations emphasize the increased cancer risk in patients with gastric atrophy and metaplasia, and the need for adequate staging in the case of high grade dysplasia, and they focus on treatment and surveillance indications and methods.
Assuntos
Mucosa Gástrica/patologia , Gastrite Atrófica/patologia , Gastrite Atrófica/terapia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/patologia , Biópsia , Medicina Baseada em Evidências , Gastrite Atrófica/diagnóstico , Gastroscopia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/economia , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Humanos , Metaplasia/patologia , Metaplasia/terapia , Pepsinogênios/sangue , Vigilância da População , Lesões Pré-Cancerosas/diagnósticoRESUMO
This consensus report of the EGILS (European Gastro-Intestinal Lymphoma Study) group includes recommendations on the management of gastric extranodal marginal zone B-cell lymphoma of MALT. They are based on data from the literature and on intensive discussions and votings of the experts during their annual meetings.
Assuntos
Linfoma de Zona Marginal Tipo Células B/diagnóstico , Neoplasias Gástricas/diagnóstico , Infecções por Helicobacter/complicações , Helicobacter pylori , Humanos , Assistência de Longa Duração/métodos , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/terapia , Estadiamento de Neoplasias , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/terapia , Resultado do TratamentoRESUMO
Presence or absence of Campylobacter spp. in water of five rivers upstream from an intake point for drinking water production was investigated, and isolates genetically compared with human, pig and poultry isolates in order to determine their source. River water and drinking water obtained from these rivers were sampled one time per month, over a period of one year, and tested for Campylobacter. Isolates were typed by PFGE. Campylobacter was not detected in treated drinking water, but 50% of the river samples were contaminated. Contamination was observed on the four seasons. In total, 297 Campylobacter isolates were collected and generated 46 PFGE profiles. Campylobacter jejuni was the most frequently detected species in samples (74.1% of the isolates), followed by Campylobacter coli (17.8%) and Campylobacter lari (8.1%). Forty-two of the 46 PFGE profiles were unique. Only one genotype was detected three times in a river during the year and four genotypes in two different rivers. When compared to animal and human Campylobacter PFGE profiles, 14, 11 and one Campylobacter genotypes from water were genetically closed to human, poultry, and pig Campylobacter genotypes, respectively. The Campylobacter population displayed a high level of genetic diversity, suggesting that contamination originated from various origins. Human, poultry and pig were sources of contamination of the river by Campylobacter. Finally, no Campylobacter were detected in drinking water, indicating that the risk of outbreaks due to consumption of drinking water is low.
Assuntos
Campylobacter/isolamento & purificação , Água Potável/microbiologia , Rios/microbiologia , Microbiologia da Água , Animais , Campylobacter/classificação , Campylobacter/genética , Campylobacter jejuni/genética , Campylobacter jejuni/isolamento & purificação , DNA Bacteriano/análise , Eletroforese em Gel de Campo Pulsado , França , Genótipo , Humanos , Reação em Cadeia da Polimerase , Aves Domésticas/microbiologia , Estações do Ano , Suínos/microbiologiaRESUMO
Helicobacter pylori is the dominant member of the gastric microbiota and has been associated with an increased risk of gastric cancer and peptic ulcers in adults. H. pylori populations have migrated and diverged with human populations, and health effects vary. Here, we describe the whole genome of the cag-positive strain V225d, cultured from a Venezuelan Piaroa Amerindian subject. To gain insight into the evolution and host adaptation of this bacterium, we undertook comparative H. pylori genomic analyses. A robust multiprotein phylogenetic tree reflects the major human migration out of Africa, across Europe, through Asia, and into the New World, placing Amerindian H. pylori as a particularly close sister group to East Asian H. pylori. In contrast, phylogenetic analysis of the host-interactive genes vacA and cagA shows substantial divergence of Amerindian from Old World forms and indicates new genotypes (e.g., VacA m3) involving these loci. Despite deletions in CagA EPIYA and CRPIA domains, V225d stimulates interleukin-8 secretion and the hummingbird phenotype in AGS cells. However, following a 33-week passage in the mouse stomach, these phenotypes were lost in isolate V225-RE, which had a 15-kb deletion in the cag pathogenicity island that truncated CagA and eliminated some of the type IV secretion system genes. Thus, the unusual V225d cag architecture was fully functional via conserved elements, but the natural deletion of 13 cag pathogenicity island genes and the truncation of CagA impaired the ability to induce inflammation.
Assuntos
Variação Genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Inflamação/metabolismo , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Linhagem Celular , Técnicas de Cocultura , Feminino , Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano , Ilhas Genômicas/genética , Ilhas Genômicas/fisiologia , Humanos , Camundongos , Dados de Sequência Molecular , FilogeniaRESUMO
BACKGROUND AND AIMS: Helicobacter pullorum is an enterohepatic Helicobacter species of avian origin detected in patients with acute diarrhoea and inflammatory bowel disease. The aim of the present study was to determine whether H pullorum exerts a direct effect on human intestinal epithelial cells in vitro and to characterise the bacterial mechanisms and the signalling pathways involved. MATERIALS AND METHODS: The proinflammatory properties of H pullorum from human and avian origins were measured on human gastric (AGS) and intestinal (CaCo-2 and HT-29) epithelial cell lines after co-culture with different H pullorum strains, and the extent of nuclear factor-kappaB (NF-kappaB) involvement was determined. RESULTS: All of the H pullorum strains tested stimulated interleukin 8 (IL8) secretion by the three cell lines. Similar results were obtained with heat-killed H pullorum. Incubation of cells with filtered H pullorum culture supernatants did not stimulate IL8 secretion. The same observation was made when bacterial adherence was inhibited by Transwell inserts. H pullorum induced NF-kappaB activation and rapid nuclear translocation as demonstrated by immunofluorescent staining and cellular fractionation. NF-kappaB involvement was confirmed by using the specific inhibitor SN50 and small interfering RNA (siRNA) which abolished H pullorum-induced IL8 production. CONCLUSIONS: H pullorum strains stimulate IL8 secretion by human gastric and intestinal epithelial cell lines. This effect requires bacterial adherence and probably lipopolysaccharides, and is mediated by NF-kappaB signalling. The present study strengthens the argument that H pullorum is a potent human pathogen and highlights its putative role in acute and chronic digestive diseases such as inflammatory bowel disease.
Assuntos
Células Epiteliais/microbiologia , Helicobacter/patogenicidade , Interleucina-8/metabolismo , NF-kappa B/metabolismo , Animais , Aderência Bacteriana/fisiologia , Western Blotting , Células CACO-2 , Núcleo Celular/metabolismo , Células Epiteliais/metabolismo , Células HT29 , Helicobacter pylori/patogenicidade , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Aves Domésticas/microbiologia , Transdução de SinaisRESUMO
INTRODUCTION: Resistance to clarithromycin and fluoroquinolones is increasing in many countries. We aimed to assess the efficacy of a tailored PCR-guided triple therapy versus an empirical triple therapy in the treatment of H. pylori infection. PATIENTS AND METHODS: French multicenter prospective open-label randomized study to assess H. pylori and resistance to clarithromycin and levofloxacin with GenoType HelicoDR® test. Patients of the control group were treated with empirical therapy of proton pump inhibitor (PPI), amoxicillin, and clarithromycin for 7 days. Patients of the experimental group with clarithromycin-susceptible strains, clarithromycin-resistant/levofloxacin-susceptible strains, and with clarithromycin-resistant/levofloxacin-resistant strains received tailored therapy of PPI, amoxicillin, and clarithromycin for 7 days, PPI, amoxicillin, and levofloxacin for 10 days, and PPI, amoxicillin, and metronidazole for 14 days, respectively. H. pylori eradication was assessed by 13C urea breath test at least 28 days after the end of treatment. RESULTS: We included 526 patients: 260 (49.4%) were randomly assigned to empirical triple therapy and 266 (50.6%) to tailored therapy. Clarithromycin and levofloxacin resistances were 23.3% and 12.8%, respectively. Follow-up urea breath test was available for 415 (78.9%) patients. Tailored therapy was superior to empirical therapy in terms of eradication (85.5% vs. 73.1%, RR=1.85, 95%CI [1.25-2.78], p=0.003). Findings were consistent in the susceptibility analysis using multiple imputation (RR=1.61, 95%CI [1.14-2.27], P=0.003) and per-protocol analysis (RR=1.89, 95%CI [0.25-2.78], p=0.003). CONCLUSION: In a country with a high level of clarithromycin resistance, tailored PCR-guided therapy was superior to empirical triple therapy for H. pylori eradication (https://www.ClinicalTrials.gov: NCT01168063).
Assuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Adulto , Idoso , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Resultado do TratamentoRESUMO
Metronidazole resistance in Helicobacter pylori has been attributed to mutations in rdxA or frxA. Insufficient data correlating RdxA and/or FrxA with the resistant phenotype, and the emergence of resistant strains with no mutations in either rdxA or frxA, indicated that the molecular basis of H. pylori resistance to metronidazole required further characterization. The rdxA and frxA genes of four matched pairs of metronidazole-susceptible and -resistant strains were sequenced. The resistant strains had mutations in either rdxA, frxA, neither gene, or both genes. The reduction rates of five substrates suggested that metabolic differences between susceptible and resistant strains cannot be explained only by mutations in rdxA and/or frxA. A more global approach to understanding the resistance phenotype was taken by employing two-dimensional gel electrophoresis combined with tandem mass spectrometry analyses to identify proteins differentially expressed by the matched pair of strains with no mutations in rdxA or frxA. Proteins involved in the oxireduction of ferredoxin were downregulated in the resistant strain. Other redox enzymes, such as thioredoxin reductase, alkyl hydroperoxide reductase, and superoxide dismutase, showed a pI change in the resistant strain. The data suggested that metronidazole resistance involved more complex metabolic changes than specific gene mutations, and they provided evidence of a role for the intracellular redox potential in the development of resistance.
Assuntos
Anti-Infecciosos , Farmacorresistência Bacteriana , Helicobacter pylori/efeitos dos fármacos , Metronidazol , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana/fisiologia , Eletroforese em Gel Bidimensional , FMN Redutase/genética , FMN Redutase/metabolismo , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Infecções por Helicobacter/microbiologia , Helicobacter pylori/enzimologia , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Humanos , Espectrometria de Massas , Metronidazol/metabolismo , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Mutação , Nitrorredutases/genética , Nitrorredutases/metabolismo , Oxirredução , ProteomaRESUMO
The publication of the complete sequence of Helicobacter pylori 26695 in 1997 and more recently that of strain J99 has provided new insight into the biology of this organism. In this review, we attempt to analyze and interpret the information provided by sequence annotations and to compare these data with those provided by experimental analyses. After a brief description of the general features of the genomes of the two sequenced strains, the principal metabolic pathways are analyzed. In particular, the enzymes encoded by H. pylori involved in fermentative and oxidative metabolism, lipopolysaccharide biosynthesis, nucleotide biosynthesis, aerobic and anaerobic respiration, and iron and nitrogen assimilation are described, and the areas of controversy between the experimental data and those provided by the sequence annotation are discussed. The role of urease, particularly in pH homeostasis, and other specialized mechanisms developed by the bacterium to maintain its internal pH are also considered. The replicational, transcriptional, and translational apparatuses are reviewed, as is the regulatory network. The numerous findings on the metabolism of the bacteria and the paucity of gene expression regulation systems are indicative of the high level of adaptation to the human gastric environment. Arguments in favor of the diversity of H. pylori and molecular data reflecting possible mechanisms involved in this diversity are presented. Finally, we compare the numerous experimental data on the colonization factors and those provided from the genome sequence annotation, in particular for genes involved in motility and adherence of the bacterium to the gastric tissue.
Assuntos
Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Infecções por Helicobacter/microbiologia , HumanosRESUMO
The aim of the present study was to propose epidemiologic cutoffs that could be used in routine practice to separate wild-type from non-wild-type Campylobacter fetus to ciprofloxacin. A total of 123 C. fetus isolates obtained from human samples were used for this purpose. Based on the determination of inhibition zone diameter, minimum inhibitory concentration, and sequencing of the quinolone resistance determining region in the gyraseA gene, for all tested isolates, the following cutoffs were proposed: ciprofloxacin-wild type if the inhibition zone diameter was ≥22 mm or the minimum inhibitory concentration was ≤0.5 mg/L.
Assuntos
Antibacterianos/farmacologia , Infecções por Campylobacter/epidemiologia , Campylobacter fetus/efeitos dos fármacos , Ciprofloxacina/farmacologia , Fluoroquinolonas/farmacologia , Infecções por Campylobacter/microbiologia , Campylobacter fetus/genética , Campylobacter fetus/isolamento & purificação , Humanos , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: The change from non-molecular to nucleic acid amplification tests (NAATs) is known to increase the detection of Clostridium difficile infection (CDI); however, the impact on stool rejection policies in clinical laboratories is unclear. The current guidelines have reinforced the importance of respecting strict conditions for performing tests on stool samples for CDI diagnosis. The purpose of this study was to estimate whether the implementation of molecular tests has resulted in changes in stool rejection policies between clinical laboratories that introduced NAATs and those that did not. RESULTS: A survey was conducted to evaluate the change in the number of stool samples rejected and the rejection criteria among 12 hospital laboratories in southwestern France before and after the switch from non-molecular tests to NAATs using retrospective data from June 1 till September 30, 2013 and the same period 2014. Four laboratories introduced NAATs as a second or third step in the process. A total of 1378 and 1297 stools samples were collected in 2013 and 2014, respectively. The mean number of rejected stool samples significantly increased (p < 0.001, Chi square test), with a total of 99 (7.1%) and 147 (11.3%) specimens rejected in 2013 and 2014, respectively. Notably, these laboratories had more stringent criteria and were no longer testing the stool samples of patients with CDI-positive results within 7 days. In contrast, there was a significant decrease in the rate of rejected stool samples (p < 0.001, Chi square test) in the five laboratories that did not adopt NAATs and a less stringent stool rejection policy. CONCLUSION: Nucleic acid amplification test implementation improved compliance with recommended stool rejection policies. Laboratories should follow the recommended laboratory algorithm for the CDI diagnosis combined with the correct stool rejection policy.