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1.
Front Immunol ; 14: 1204433, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37622126

RESUMO

Background: Increased titers of autoantibodies targeting the G-protein-coupled receptors angiotensin II type 1 receptor (AT1R) and endotelin-1 type A receptor (ETAR) are associated with severe coronavirus disease 2019 (COVID-19) infection. The aim of this study was to determine whether 1) these antibodies are specifically related to COVID-19 disease pathogenesis or increased during any severe respiratory illness, 2) if they are formed during illness, and 3) if they correlate with inflammatory markers or long-term symptoms. Methods: Antibodies against AT1R, ETAR, and antinuclear antibodies (ANAs) were measured in n=40 prospectively enrolled COVID-19 patients and n=207 COVID-19 patients included in a biobank. Clinical and laboratory findings were prospectively and retrospectively assessed in both cohorts, and results were combined for analysis. The presence of auto-antibodies against AT1R or ETAR in peripheral blood was compared between hospitalized patients with COVID-19 and controls (n=39). Additionally, AT1R and ETAR titers were compared between patients with an unfavorable disease course, defined as intensive care admission and/or death during hospital admission (n=121), to those with a favorable disease course (n=126). A subset of intubated patients with severe COVID-19 were compared to intubated patients with acute respiratory distress syndrome (ARDS) due to any other cause. Results: Significantly increased AT1R and ETAR antibody titers were found in COVID-19 patients compared to controls, while titers were equal between favorable and unfavorable COVID-19 disease course groups. On ICU, intubated patients with COVID-19 had significantly increased AT1R and ETAR titers compared to patients with ARDS due to any other cause. The titers did not correlate with baseline inflammatory markers during admission or with diffusion capacity, cognitive impairment, or fatigue measured at 3 months follow-up. Conclusions: In patients hospitalized for COVID-19, antibodies against AT1R and ETAR are increased compared to controls and patients with ARDS due to other causes than COVID-19. The baseline antibody titers do not correlate with inflammatory markers or long-term symptoms in this study.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Receptor de Endotelina A , Receptor Tipo 1 de Angiotensina , Estudos Retrospectivos , Autoanticorpos
2.
TH Open ; 7(3): e217-e225, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37501780

RESUMO

Background Fibrinogen variants as a result of alternative messenger RNA splicing or protein degradation can affect fibrin(ogen) functions. The levels of these variants might be altered during coronavirus disease 2019 (COVID-19), potentially affecting disease severity or the thrombosis risk. Aim To investigate the levels of fibrinogen variants in plasma of patients with COVID-19. Methods In this case-control study, we measured levels of functional fibrinogen using the Clauss assay. Enzyme-linked immunosorbent assays were used to measure antigen levels of total, intact (nondegraded Aα chain), extended Aα chain (α E ), and γ' fibrinogen in healthy controls, patients with pneumococcal infection in the intensive care unit (ICU), ward patients with COVID-19, and ICU patients with COVID-19 (with and without thrombosis, two time points). Results Healthy controls and ward patients with COVID-19 ( n = 10) showed similar fibrinogen (variant) levels. ICU patients with COVID-19 who later did ( n = 19) or did not develop thrombosis ( n = 18) and ICU patients with pneumococcal infection ( n = 6) had higher absolute levels of functional, total, intact, and α E fibrinogen than healthy controls ( n = 7). The relative α E fibrinogen levels were higher in ICU patients with COVID-19 than in healthy controls, while relative γ' fibrinogen levels were lower. After diagnosis of thrombosis, only the functional fibrinogen levels were higher in ICU patients with COVID-19 and thrombosis than in those without, while no differences were observed in the other fibrinogen variants. Conclusion Our results show that severe COVID-19 is associated with increased levels of α E fibrinogen and decreased relative levels of γ' fibrinogen, which may be a cause or consequence of severe disease, but this is not associated with the development of thrombosis.

3.
Ned Tijdschr Geneeskd ; 1672023 05 31.
Artigo em Holandês | MEDLINE | ID: mdl-37289862

RESUMO

Climate change directly and indirectly contributes to the emergence of vector and water borne infections. Other infectious diseases may be introduced to new geographical areas as a result of globalisation and changing human behaviour. Despite the still low absolute risk, the pathogenicity of some of these infections creates a significant challenge for clinicians. Awareness of changing disease epidemiology helps in timely recognition of such infections. Vaccination guidelines for emerging vaccine-preventable diseases, such as tick-borne encephalitis and leptospirosis, may need to be updated.


Assuntos
Doenças Transmissíveis , Encefalite Transmitida por Carrapatos , Humanos , Mudança Climática , Doenças Transmissíveis/epidemiologia , Europa (Continente)/epidemiologia , Encefalite Transmitida por Carrapatos/epidemiologia
4.
Sci Adv ; 9(11): eade6675, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36921041

RESUMO

Reactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Here, we investigated the impact of the BAF complex inhibitor pyrimethamine on the reservoir of people living with HIV-1 (PLWH). Twenty-eight PLWH on suppressive antiretroviral therapy were randomized (1:1:1:1 ratio) to receive pyrimethamine, valproic acid, both, or no intervention for 14 days. The primary end point was change in cell-associated unspliced (CA US) HIV-1 RNA at days 0 and 14. We observed a rapid, modest, and significant increase in (CA US) HIV-1 RNA in response to pyrimethamine exposure, which persisted throughout treatment and follow-up. Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine. Pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir. These data demonstrate that the licensed drug pyrimethamine can be repurposed as a BAF complex inhibitor to reverse HIV-1 latency in vivo in PLWH, substantiating its potential advancement in clinical studies.


Assuntos
Infecções por HIV , HIV-1 , Humanos , Linfócitos T CD4-Positivos , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Pirimetamina/farmacologia , Pirimetamina/uso terapêutico , RNA , Ácido Valproico/farmacologia , Ativação Viral , Latência Viral
5.
Int J Infect Dis ; 122: 665-668, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35842214

RESUMO

OBJECTIVES: SARS-CoV-2 Omicron variants BA.1 and BA.2 seem to show reduced clinical severity compared with earlier variants. Therefore, we aimed to assess and classify the cause of hospitalization for patients with COVID-19 identified with these Omicron variants in our hospital. METHODS: A retrospective analysis was performed on all patients identified with the SARS-CoV-2 Omicron variant between December 23, 2021, and February 27, 2022. Patients with a positive SARS-CoV-2 polymerase chain reaction (PCR) upon clinical admission or during clinical admission were classified into four categories: (1) primary COVID-19, (2) admission-contributing COVID-19, (3) incidental COVID-19, and (4) undetermined COVID-19. RESULTS: We classified 172 COVID-19 Omicron patient admissions, including 151 adult and 21 pediatric patients. Of the adult patients, 45% were primary COVID-19 cases, 21% were admission-contributing, 31% were incidental, and 3% were undetermined. Of the pediatric patients, 19% were primary COVID-19 cases, 29% were admission-contributing, 38% were incidental, and 14% were undetermined. CONCLUSION: In the evolving landscape of COVID-19, the number of hospitalized patients with COVID-19 should be interpreted with caution. The different patient categories should be considered in public health policy decision-making and when informing the general public.


Assuntos
COVID-19 , Adulto , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste para COVID-19 , Criança , Hospitalização , Humanos , Reação em Cadeia da Polimerase , Estudos Retrospectivos , SARS-CoV-2/genética , Centros de Atenção Terciária
6.
BMJ Open ; 11(9): e051468, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531219

RESUMO

OBJECTIVES: Develop simple and valid models for predicting mortality and need for intensive care unit (ICU) admission in patients who present at the emergency department (ED) with suspected COVID-19. DESIGN: Retrospective. SETTING: Secondary care in four large Dutch hospitals. PARTICIPANTS: Patients who presented at the ED and were admitted to hospital with suspected COVID-19. We used 5831 first-wave patients who presented between March and August 2020 for model development and 3252 second-wave patients who presented between September and December 2020 for model validation. OUTCOME MEASURES: We developed separate logistic regression models for in-hospital death and for need for ICU admission, both within 28 days after hospital admission. Based on prior literature, we considered quickly and objectively obtainable patient characteristics, vital parameters and blood test values as predictors. We assessed model performance by the area under the receiver operating characteristic curve (AUC) and by calibration plots. RESULTS: Of 5831 first-wave patients, 629 (10.8%) died within 28 days after admission. ICU admission was fully recorded for 2633 first-wave patients in 2 hospitals, with 214 (8.1%) ICU admissions within 28 days. A simple model-COVID outcome prediction in the emergency department (COPE)-with age, respiratory rate, C reactive protein, lactate dehydrogenase, albumin and urea captured most of the ability to predict death. COPE was well calibrated and showed good discrimination for mortality in second-wave patients (AUC in four hospitals: 0.82 (95% CI 0.78 to 0.86); 0.82 (95% CI 0.74 to 0.90); 0.79 (95% CI 0.70 to 0.88); 0.83 (95% CI 0.79 to 0.86)). COPE was also able to identify patients at high risk of needing ICU admission in second-wave patients (AUC in two hospitals: 0.84 (95% CI 0.78 to 0.90); 0.81 (95% CI 0.66 to 0.95)). CONCLUSIONS: COPE is a simple tool that is well able to predict mortality and need for ICU admission in patients who present to the ED with suspected COVID-19 and may help patients and doctors in decision making.


Assuntos
COVID-19 , Serviço Hospitalar de Emergência , Mortalidade Hospitalar , Hospitais , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos , SARS-CoV-2
7.
mSphere ; 6(3): e0031121, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34047654

RESUMO

COVID-19 is associated with a wide range of extrarespiratory complications, of which the pathogenesis is currently not fully understood. However, both systemic spread and systemic inflammatory responses are thought to contribute to the systemic pathogenesis. In this study, we determined the temporal kinetics of viral RNA in serum (RNAemia) and the associated inflammatory cytokines and chemokines during the course of COVID-19 in hospitalized patients. We show that RNAemia can be detected in 90% of the patients who develop critical disease, compared to 50% of the patients who develop moderate or severe disease. Furthermore, RNAemia lasts longer in patients who develop critical disease. Elevated levels of interleukin-10 (IL-10) and MCP-1-but not IL-6-are associated with viral load in serum, whereas higher levels of IL-6 in serum were associated with the development of critical disease. In conclusion, RNAemia is common in hospitalized patients, with the highest frequency and duration in patients who develop critical disease. The fact that several cytokines or chemokines are directly associated with the presence of viral RNA in the circulation suggests that the development of RNAemia is an important factor in the systemic pathogenesis of COVID-19. IMPORTANCE Severe COVID-19 can be considered a systemic disease as many extrarespiratory complications occur. However, the systemic pathogenesis is poorly understood. Here, we show that the presence of viral RNA in the blood (RNAemia) occurs more frequently in patients who develop critical disease, compared to patients with moderate or severe disease. In addition, RNAemia is associated with increased levels of inflammatory cytokines and chemokines, like MCP-1 and IL-10, in serum during the course of disease. This suggests that extrarespiratory spread of SARS-CoV-2 contributes to systemic inflammatory responses, which are an important factor in the systemic pathogenesis of COVID-19.


Assuntos
COVID-19/imunologia , Citocinas/sangue , RNA Viral/sangue , SARS-CoV-2/genética , COVID-19/etiologia , COVID-19/virologia , Hospitalização , Humanos , Cinética , Índice de Gravidade de Doença
8.
Eur J Clin Microbiol Infect Dis ; 40(10): 2207-2209, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33713005

RESUMO

Mortality from COVID-19 has been particularly high in elderly patients on mechanical ventilation. Treatment outcomes for patients with do-not-intubate (DNI) status are unknown. One hundred patients admitted to the non-ICU ward during the "first wave" were retrospectively analyzed. Mortality rate was 49% in patients with a DNI order. This subgroup was characterized by significantly higher age, more comorbidity, and care dependency. Mortality among DNI patients was three times higher than other patients, but not higher than some of the published mortality rates for elderly mechanically ventilated patients. Advanced care planning is essential in COVID-19 to assist patient autonomy and prevent non-beneficial medical interventions.


Assuntos
COVID-19/mortalidade , COVID-19/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Mortalidade Hospitalar , Humanos , Intubação , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Retrospectivos , Adulto Jovem
9.
Open Forum Infect Dis ; 7(2): ofaa020, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32055637

RESUMO

We report yellow fever infection in a Dutch traveler returning from Brazil. Yellow fever virus (YFV) was identified in serum and urine samples over a period of 1 month. Yellow fever virus genome sequences from the patient clustered with recent Brazilian YFV and showed with limited nucleotide changes during the resolving infection.

10.
Viruses ; 11(4)2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974852

RESUMO

Several case reports have described hypopituitarism following orthohantavirus infection, mostly following Puumala virus. The pathogenesis of this seemingly rare complication of orthohantavirus infection remains unknown. This review explores the possible pathophysiological mechanisms of pituitary damage due to orthohantavirus infection. In only three out of the 28 reported cases, hypopituitarism was detected during active infection. In the remaining cases, detection of pituitary damage was delayed, varying from two months up to thirteen months post-infection. In these cases, hypopituitarism remained undetected during the acute phase of infection or only occurred weeks to months post infection. Both ischemic and hemorrhagic damage of the pituitary gland have been detected in radiographic imaging and post-mortem studies in the studied case reports series. Ischemic damage could be caused by hypotension and/or vasospasms during the acute phase of hemorrhagic fever with renal syndrome (HFRS) while hemorrhage could be caused by thrombocytopenia, thrombopathy, and other known causes of coagulation disorders during orthohantavirus infection. Also, hypophysitis due to the presence of auto-antibodies have been suggested in the literature. In conclusion, a significant number of case reports and series describe hypopituitarism after orthohantavirus infection. In most cases hypopituitarism was diagnosed with a delay and therefore could very well be underreported. Clinicians should be aware of this potential endocrine complication, with substantial morbidity, and if unrecognized, significant mortality.


Assuntos
Febre Hemorrágica com Síndrome Renal/complicações , Hipopituitarismo/etiologia , Orthohantavírus/patogenicidade , Febre Hemorrágica com Síndrome Renal/diagnóstico , Febre Hemorrágica com Síndrome Renal/patologia , Febre Hemorrágica com Síndrome Renal/fisiopatologia , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/patologia , Hipopituitarismo/fisiopatologia , Hipófise/patologia , Hipófise/fisiopatologia , Virus Puumala/patogenicidade
11.
Ned Tijdschr Geneeskd ; 1622018 09 24.
Artigo em Holandês | MEDLINE | ID: mdl-30358370

RESUMO

BACKGROUND: Since 2016 outbreaks of yellow fever are reported in Brazil. This is a risk to unvaccinated travellers in that area. CASE DESCRIPTION: In early January, an unvaccinated traveller returning from São Paulo attended our outpatient clinic complaining of symptoms later diagnosed as yellow fever. The disease manifested itself as fever, lower back pain, nausea and highly elevated liver enzymes. A yellow fever infection has multiple stages. The first stage is acute infection which merges into the second stage which is when improvement occurs. Either improvement continues or transfers into a third stage which is characterized by multi-organ failure. In this particular patient, stage three did not occur. CONCLUSION: The goal of this case report is to show that vaccination against yellow fever is the most important preventive measure when travelling to an area where the yellow fever virus is in circulation. Yellow fever should not be forgotten in the differential diagnosis of a traveller with fever.


Assuntos
Viagem , Vacinação , Vacina contra Febre Amarela , Febre Amarela/prevenção & controle , Vírus da Febre Amarela , Brasil/epidemiologia , Surtos de Doenças , Febre , Humanos , Fígado/enzimologia , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Náusea/diagnóstico , Náusea/etiologia , Febre Amarela/complicações , Febre Amarela/diagnóstico , Febre Amarela/epidemiologia
12.
United European Gastroenterol J ; 5(6): 868-879, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29026601

RESUMO

BACKGROUND: Fecal microbiota transfer (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI), but data on procedure-related complications and long-term outcome are scarce. METHODS: All patients treated with FMT for recurrent CDI at the Academic Medical Center between July 2010 and January 2016 were included. FMT was performed according to the FECAL trial protocol: administration of fresh donor feces (related or unrelated donor) through a duodenal tube after pre-treatment with vancomycin and bowel lavage. We collected information on FMT-related complications, recurrent CDI, and short- and long-term adverse events by telephone interviews using a structured questionnaire at three months after FMT, and at the time of data collection of this study. RESULTS: In total, 39 patients were treated with FMT. The primary cure rate (no recurrence ≤8 weeks after one infusion with donor feces) was 82% (32 of 39 patients). Of the seven patients with recurrent CDI after FMT, four were cured by antibiotic therapy alone (fidaxomicin in three patients, metronidazole in one patient) and three by repeat FMT. Peri-procedural complications occurred in five patients, comprising fecal regurgitation or vomiting. One patient died one week post-FMT due to pneumonia; a causal relation with FMT could not be excluded. The follow-up period ranged between 3 and 68 months. No long-term side effects were reported. CONCLUSIONS: Our data underline the efficacy of FMT as treatment for recurrent CDI. Importantly, it is possible to cure post-FMT recurrences with antibiotic therapy alone. Peri-procedural complications do occur and should be closely monitored to help identify high-risk patients. To minimize the risk of complications, all FMT candidates should be evaluated to assess the most ideal delivery method.

13.
ISME J ; 8(8): 1621-33, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24577353

RESUMO

Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time. Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies.


Assuntos
Clostridioides difficile , Infecções por Clostridium/microbiologia , Fezes/microbiologia , Microbiota , Infecções por Clostridium/terapia , Humanos , Intestinos/microbiologia , Filogenia , Recidiva
14.
J Hepatol ; 60(4): 824-31, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24316517

RESUMO

BACKGROUND & AIMS: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism. METHODS: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured. RESULTS: Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal bile acid concentrations were predominantly associated with altered Firmicutes. Finally, administration of vancomycin decreased peripheral insulin sensitivity (p<0.05). Amoxicillin did not affect any of these parameters. CONCLUSIONS: Oral administration of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid and glucose metabolism in humans. This trial is registered at the Dutch Trial Register (NTR2566).


Assuntos
Antibacterianos/administração & dosagem , Ácidos e Sais Biliares/metabolismo , Resistência à Insulina , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Microbiota/efeitos dos fármacos , Vancomicina/administração & dosagem , Administração Oral , Adulto , Idoso , Animais , Antibacterianos/efeitos adversos , Ácidos e Sais Biliares/sangue , Fezes/química , Fezes/microbiologia , Glucose/metabolismo , Humanos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/microbiologia , Camundongos , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/microbiologia , Método Simples-Cego , Vancomicina/efeitos adversos
15.
Curr Opin Gastroenterol ; 30(1): 34-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24241245

RESUMO

PURPOSE OF REVIEW: To review the current evidence on fecal microbiota transplantations (FMTs) for recurrent Clostridium difficile infections (CDIs), metabolic syndrome and inflammatory bowel disease. RECENT FINDINGS: Recently, a randomized trial confirmed the efficacy of this treatment strategy in patients with recurrent CDI. For other disorders, evidence is still limited. To date, studies have been performed to try and influence the course of metabolic syndrome and inflammatory bowel disease. SUMMARY: There is increasing interest in the role of altered microbiota in the development of a myriad of diseases. Together with new insights comes an interest in influencing this altered microbiota as a potential target for therapy. FMTs are effective against recurrent CDI, a disorder caused by disruption of the normal microbiota. Restoration of intestinal flora and thereby restoration of colonization resistance is thought to be the mechanism responsible for cure. With the developments in FMT and the extension of this treatment modality to both intestinal and extra-intestinal diseases, a new field of targeted therapy awaits. The ultimate goal is the development of powerful probiotic regimens that can replace FMT. Currently, FMT should only be given in a strict experimental setting for other conditions than CDI.


Assuntos
Enterocolite Pseudomembranosa/terapia , Fezes/microbiologia , Microbiota , Transplante de Tecidos/métodos , Protocolos Clínicos , Seleção do Doador/métodos , Humanos , Doenças Inflamatórias Intestinais/terapia , Intestinos/microbiologia , Síndrome Metabólica/terapia , Recidiva , Transplante de Tecidos/efeitos adversos
16.
Ned Tijdschr Geneeskd ; 157(48): A6580, 2013.
Artigo em Holandês | MEDLINE | ID: mdl-24279951

RESUMO

Currently available broad spectrum antibiotics are not sufficiently effective against recurrent Clostridium difficile infections (CDI). Donor faecal microbiota transplantation is a very effective treatment for second and recurrent infection but is time-consuming and requires careful screening of donors. The new narrow spectrum antibiotic fidaxomicin is a good alternative in a first CDI or a first recurrence, but treatment is expensive and there are no data on its effectiveness in a second or later recurrence. Fidaxomicin is less effective against infections caused by the Ribotype 027 strain, a virulent strain that is regularly encountered in the Netherlands. The effectiveness of various other promising narrow spectrum antibiotics is currently being investigated. Medications that support the gut flora or the immune system seem to offer new perspectives. Expectations for the currently available probiotic preparations and toxin binders are not high.


Assuntos
Antibacterianos/uso terapêutico , Clostridioides difficile , Enterocolite Pseudomembranosa/tratamento farmacológico , Probióticos/uso terapêutico , Aminoglicosídeos/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/patogenicidade , Infecções por Clostridium/tratamento farmacológico , Fezes/microbiologia , Fidaxomicina , Humanos , Países Baixos , Recidiva , Resultado do Tratamento
18.
N Engl J Med ; 368(5): 407-15, 2013 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-23323867

RESUMO

BACKGROUND: Recurrent Clostridium difficile infection is difficult to treat, and failure rates for antibiotic therapy are high. We studied the effect of duodenal infusion of donor feces in patients with recurrent C. difficile infection. METHODS: We randomly assigned patients to receive one of three therapies: an initial vancomycin regimen (500 mg orally four times per day for 4 days), followed by bowel lavage and subsequent infusion of a solution of donor feces through a nasoduodenal tube; a standard vancomycin regimen (500 mg orally four times per day for 14 days); or a standard vancomycin regimen with bowel lavage. The primary end point was the resolution of diarrhea associated with C. difficile infection without relapse after 10 weeks. RESULTS: The study was stopped after an interim analysis. Of 16 patients in the infusion group, 13 (81%) had resolution of C. difficile-associated diarrhea after the first infusion. The 3 remaining patients received a second infusion with feces from a different donor, with resolution in 2 patients. Resolution of C. difficile infection occurred in 4 of 13 patients (31%) receiving vancomycin alone and in 3 of 13 patients (23%) receiving vancomycin with bowel lavage (P<0.001 for both comparisons with the infusion group). No significant differences in adverse events among the three study groups were observed except for mild diarrhea and abdominal cramping in the infusion group on the infusion day. After donor-feces infusion, patients showed increased fecal bacterial diversity, similar to that in healthy donors, with an increase in Bacteroidetes species and clostridium clusters IV and XIVa and a decrease in Proteobacteria species. CONCLUSIONS: The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin. (Funded by the Netherlands Organization for Health Research and Development and the Netherlands Organization for Scientific Research; Netherlands Trial Register number, NTR1177.).


Assuntos
Antibacterianos/uso terapêutico , Clostridioides difficile , Diarreia/terapia , Fezes/microbiologia , Vancomicina/uso terapêutico , Administração Oral , Idoso , Terapia Combinada , Diarreia/tratamento farmacológico , Diarreia/microbiologia , Duodeno , Feminino , Humanos , Intubação Gastrointestinal , Masculino , Metagenoma , Pessoa de Meia-Idade , Recidiva , Irrigação Terapêutica
19.
Gastroenterology ; 143(4): 913-6.e7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22728514

RESUMO

Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 µmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776).


Assuntos
Glicemia/metabolismo , Fezes/microbiologia , Resistência à Insulina , Intestino Delgado/microbiologia , Síndrome Metabólica/terapia , Metagenoma , Adulto , Alcaligenes faecalis , Bacteroidetes , Índice de Massa Corporal , Clostridium , Escherichia coli , Eubacterium , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Humanos , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Oxalobacter formigenes , Estatísticas não Paramétricas
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