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2.
Sci Immunol ; 7(71): eabm1803, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35594341

RESUMO

Clostridium species are a group of Gram-positive bacteria that cause diseases in humans, such as food poisoning, botulism, and tetanus. Here, we analyzed 10 different Clostridium species and identified that Clostridium septicum, a pathogen that causes sepsis and gas gangrene, activates the mammalian cytosolic inflammasome complex in mice and humans. Mechanistically, we demonstrate that α-toxin secreted by C. septicum binds to glycosylphosphatidylinositol (GPI)-anchored proteins on the host plasma membrane, oligomerizing and forming a membrane pore that is permissive to efflux of magnesium and potassium ions. Efflux of these cytosolic ions triggers the activation of the innate immune sensor NLRP3, inducing activation of caspase-1 and gasdermin D, secretion of the proinflammatory cytokines interleukin-1ß and interleukin-18, pyroptosis, and plasma membrane rupture via ninjurin-1. Furthermore, α-toxin of C. septicum induces rapid inflammasome-mediated lethality in mice and pharmacological inhibition of the NLRP3 inflammasome using MCC950 prevents C. septicum-induced lethality. Overall, our results reveal that cytosolic innate sensing of α-toxin is central to the recognition of C. septicum infection and that therapeutic blockade of the inflammasome pathway may prevent sepsis and death caused by toxin-producing pathogens.


Assuntos
Toxinas Bacterianas , Proteínas Ligadas por GPI , Inflamassomos , Animais , Toxinas Bacterianas/metabolismo , Clostridium septicum/química , Proteínas Ligadas por GPI/metabolismo , Glicosilfosfatidilinositóis/metabolismo , Inflamassomos/metabolismo , Mamíferos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sepse
6.
J Vasc Surg ; 76(2): 595-604.e1, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35358668

RESUMO

BACKGROUND: Clostridium septicum bacteremia is often associated with occult malignancies (approximately 80%), especially of the right colon. Furthermore, inflammation of the aortic wall can rapidly lead to aneurysm induction through bacterial seeding into atheromatous lesions with consecutive life-threatening rupture. We summarize all published data on this rare and lethal disease to evaluate therapeutic approaches and give valid treatment recommendations because there are no guidelines. METHODS: A systematic review of the literature was conducted screening EMBASE and MEDLINE databases following the PRISMA guidelines with search period from first description to August 25, 2021. RESULTS: There were 72 cases of C septicum aortitis reported in 64 publications. Endovascular aortic repair (EVAR) was performed in a minority of patients (n = 6) unfit for surgery but lacked long-term survivors. Antibiotic treatment was beneficial in a bridge to surgery concept, but up to now harbored a 6-month mortality rate of 100% (median overall survival, 0.5 months) when no additional aortic repair was performed. Open aortic repair was the only potential curative approach but was accompanied with a 90-day-mortality of 26.7% (4/15). CONCLUSIONS: Open aortic repair combined with perioperative antibiotic treatment should be offered to all patients as the only potentially curative approach. If applicable, resection of a coexisting colonic tumor should be performed after successful aortic repair. Alternatively, long-term antibiotic treatment can be offered to patients unfit for surgery in a palliative setting. Endovascular aortic repair has been performed on a minority of patients with a high risk for stent graft infection and should remain a salvage strategy when therapeutic pressure demands acute intervention in patients unfit for surgery.


Assuntos
Aneurisma da Aorta Abdominal , Aortite , Implante de Prótese Vascular , Clostridium septicum , Procedimentos Endovasculares , Antibacterianos/uso terapêutico , Aorta/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Aortite/diagnóstico por imagem , Aortite/cirurgia , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Humanos , Stents , Resultado do Tratamento
8.
Ann R Coll Surg Engl ; 104(4): e95-e97, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34825573

RESUMO

Necrotising infections remain challenging to surgeons, both in diagnosis and management. Timely recognition and treatment remain vital. We report a presentation of limb ischaemia with no apparent precipitating factors, in a systemically stable patient, due to atraumatic Clostridium septicum myonecrosis. This article demonstrates the use of rapid cross-sectional imaging in finding an undiagnosed bowel cancer as a basis for this type of infection. Rapid cross-sectional imaging may be utilised where there is doubt about the underlying pathology of upper limb ischaemia. Patients whose cultures grow Clostridium septicum must be investigated for malignancy.


Assuntos
Infecções por Clostridium , Clostridium septicum , Neoplasias Colorretais , Gangrena Gasosa , Infecções por Clostridium/complicações , Infecções por Clostridium/diagnóstico , Gangrena Gasosa/diagnóstico , Gangrena Gasosa/etiologia , Gangrena Gasosa/terapia , Humanos , Isquemia/diagnóstico , Isquemia/etiologia
9.
Ophthalmic Plast Reconstr Surg ; 38(1): e6-e10, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34593715

RESUMO

A previously healthy 62-year-old African American female presented with a fulminant orbital cellulitis of the right eye with diffuse scleritis and orbital inflammation extending to the optic chiasm on neuroimaging. She was taken for an emergent orbitotomy with an orbital fat biopsy and started on broad-spectrum intravenous (IV) and topical antibiotics. Within 36 hours of presentation, scleral thinning and a corneal melt ensued, ending in enucleation. Intraoperative cultures were positive for Clostridium septicum, leading to a systemic work-up exposing a previously undiagnosed colon adenocarcinoma and metastatic multiple myeloma.


Assuntos
Clostridium septicum , Neoplasias do Colo , Mieloma Múltiplo , Panoftalmite , Neoplasias do Colo/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Quiasma Óptico
10.
Ocul Immunol Inflamm ; 30(2): 348-354, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32966149

RESUMO

PURPOSE: To describe the presentation and clinical course of a case of endogenous endophthalmitis caused by Clostridium septicum, an anaerobic and gram positive bacteria. METHODS: Observational report of a clinical case presented in Spain. CLINICAL CASE: A 61-year-old male patient was referred to our hospital with a diagnosis of endophthalmitis of his left eye since ten days prior to presentation, and a history of poor response to medical treatment. Evisceration was performed, and C. septicum was isolated from a sample of the vitreous humor. Fourteen days after surgery, the patient returned with orbital cellulitis, and exenteration was performed. Forty-two days after initial presentation, colonoscopy revealed an adenocarcinoma of the proximal colon. Surgical resection of the tumor was performed, and clinical recovery was achieved. CONCLUSIONS: iSystemic C. septicum infection without a traumatic cause has been associated with malignancy, although an initial presentation of endophthalmitis has rarely been reported. In cases of clostridial endogenous endophthalmitis, investigation for colorectal carcinoma is indicated.


Assuntos
Adenocarcinoma , Infecções por Clostridium , Clostridium septicum , Neoplasias Colorretais , Endoftalmite , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Infecções por Clostridium/complicações , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Clostridium septicum/fisiologia , Neoplasias Colorretais/complicações , Endoftalmite/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto
11.
Prague Med Rep ; 122(3): 212-215, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34606433

RESUMO

A fatal case of 67-year-old female with metastatic breast cancer on chemotherapy complicated with febrile neutropenia, colitis and sepsis due to Clostridium septicum is presented. Important clinical symptoms, laboratory and radiology findings together with therapy and outcome of neuropenic colitis are also discussed.


Assuntos
Bacteriemia , Neoplasias da Mama , Infecções por Clostridium , Clostridium septicum , Colite , Idoso , Bacteriemia/diagnóstico , Neoplasias da Mama/complicações , Infecções por Clostridium/complicações , Infecções por Clostridium/diagnóstico , Colite/diagnóstico , Colite/etiologia , Feminino , Humanos
13.
BMC Infect Dis ; 21(1): 957, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530753

RESUMO

BACKGROUND: Gas gangrene is usually manifested as myonecrosis and subcutaneous gas accumulation, but rarely manifested as arterial occlusion or pneumatosis in the right ventricle and the pulmonary artery. CASE PRESENTATION: We report a case of gas gangrene caused by Clostridium septicum. The patient developed gas gangrene after being pecked by a chicken but turned for the better following antibiotic treatment and debriment. Imaging test revealed a rare occlusion of the right femoral artery and pneumatosis in the right ventricle and the main pulmonary artery. CONCLUSIONS: In the presence of gas gangrene, special care must be taken to prevent against the formation of circulatory air embolism. The gas gangrene-induced gangrene in the limb of this patient might be attributed to the combined action of infection and arterial occlusion. MDT (Multidisciplinary team)-Green Channel mode is conductive to treatment success of gas gangrene.


Assuntos
Clostridium septicum , Gangrena Gasosa , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/cirurgia , Gangrena/etiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Extremidade Inferior , Artéria Pulmonar/diagnóstico por imagem
14.
Anaerobe ; 72: 102445, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34571154

RESUMO

Clostridial myonecrosis is a medical and surgical emergency which requires early and aggressive intervention to reduce mortality. We report a rare case of Clostridium septicum myonecrosis that disseminated hematogenously from a gastric perforation. The patient was afebrile and hemodynamically stable upon admission. He rapidly developed spontaneous clostridial myonecrosis and succumbed to septic shock 36 hours after presentation. In our extensive literature review this is the only case with blood cultures confirming Clostridium septicum bacteremia with a surgically confirmed gastric perforation source in the setting of spontaneous clostridial myonecrosis.


Assuntos
Infecções por Clostridium/diagnóstico , Infecções por Clostridium/etiologia , Clostridium septicum , Gangrena Gasosa/diagnóstico , Gangrena Gasosa/etiologia , Idoso , Biomarcadores , Gerenciamento Clínico , Suscetibilidade a Doenças , Serviços Médicos de Emergência , Evolução Fatal , Humanos , Masculino , Úlcera Péptica Perfurada/complicações , Úlcera Péptica Perfurada/diagnóstico , Úlcera Péptica Perfurada/cirurgia , Complicações Pós-Operatórias , Radiografia Torácica , Tomografia Computadorizada por Raios X
15.
Anaerobe ; 71: 102406, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34214691

RESUMO

Clostridium septicum endophthalmitis is an extremely rare infection with only a few cases reported in the literature. It has an endogenous origin and is associated with gastrointestinal and haematological malignancies. We present the case of a 62-year-old male who presented this infection as the first manifestation of a colon adenocarcinoma.


Assuntos
Infecções por Clostridium/microbiologia , Clostridium septicum/isolamento & purificação , Neoplasias do Colo/complicações , Endoftalmite/microbiologia , Infecções por Clostridium/diagnóstico , Clostridium septicum/genética , Clostridium septicum/fisiologia , Endoftalmite/etiologia , Humanos , Masculino , Pessoa de Meia-Idade
16.
Vaccine ; 39(35): 4949-4956, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34312008

RESUMO

Clostridium septicum (CS) is a pathogen that can cause the death of animals in livestock worldwide through its main virulence factor, alpha-toxin (ATX). The aspects involved in diseases caused by ATX, such as economic impact, prevalence, and rapid clinical course, require that animals should be systematically immunized. This review provides an overview of CS in livestock farming and discusses current immunization methods. Currently, commercial vaccines available against CS involve the cultivation and inactivation of microorganisms and toxins using a time-consuming, expensive, and high biological risk-carrying production platform, and some have been reported to be ineffective. An alternative to this process is the recombinant DNA technology, although recombinant ATX obtained thus far is no longer efficient in stimulating protective antibody titers despite improvements in the production methods. On the other hand, immunized animals have highly favorable levels of survival when subjected to challenge tests, suggesting that high titers of circulating serum antibodies may not be representative of protection after immunization and that the non-immune cellular defenses associated with the particularities of the mechanism of action of ATX may be involved in the immune response of the host. To contribute to the future of global livestock farming through the development of more efficient recombinant vaccines, we suggest novel perspectives and strategies, such as the location of immunodominant epitopes, expression of relevant functional domains, and construction of chimeras, in the rational design of recombinant ATX.


Assuntos
Toxinas Bacterianas , Infecções por Clostridium , Clostridium septicum , Animais , Anticorpos Antibacterianos , Vacinas Bacterianas , Infecções por Clostridium/prevenção & controle
17.
Pharmeur Bio Sci Notes ; 2021: 101-156, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34078535

RESUMO

During the production of clostridial vaccines large numbers of mice are used for various in-process control tests. Replacement in vitro assays had been developed for the testing of the toxins and toxoids of several clostridial species, but none of these assays had been assessed in an international collaborative study. Under the common aegis of the European Partnership for Alternative Approaches to Animal Testing (EPAA) and of the European Directorate for the Quality of Medicines & HealthCare (EDQM), a project on clostridial vaccines for veterinary use was started as part of the EDQM-co-ordinated Biological Standardisation Programme (BSP). Within the framework of this project (coded BSP130) a collaborative study was organised to evaluate Vero cell-based alternative methods to the current mouse tests used to measure: i) the toxicity of Clostridium septicum toxin, ii) the absence of toxicity of C. septicum toxoid and iii) the antigenicity of C. septicum toxoid. The principal aims of the study were to determine the repeatability and reproducibility of the in vitro assays and to demonstrate concordance of the in vitro and current in vivo tests. The study results demonstrated good concordance, but the information gathered through the study (later on called Part 1) and the participants' workshop prompted the extension of the project in order to further optimise the in vitro protocols and improve their repeatability and reproducibility, which were comparable to but not better than those of the in vivo assays in Part 1. The 3 in vitro assays to be optimised in the extension of the BSP130 project were : i) the in vitro toxin neutralisation equivalence plus (TNE+), as a replacement for the in vivo minimum lethal dose (MLD) test for quantification of the toxicity of toxin; ii) the in vitro MLD, as a replacement for the in vivo MLD test for detection of residual toxicity associated with toxoid; iii) the in vitro total combining power (TCP), as a replacement for the in vivo TCP test for quantification of the antigenicity of toxoid. At this point, the Analytical Method Transfer Laboratory of Ceva-Phylaxia (Hungary), supported by the project management team, developed suitable SOPs for the 3 in vitro assays. These optimised methods were further assessed in BSP130 through a second international collaborative study (Part 2) aimed at defining repeatability and reproducibility in different laboratories and determining the levels of improvement compared with the original in vivo tests and the initial in vitro assays used in Part 1 of the project. Fourteen laboratories, comprising 4 public sector and 10 manufacturers' medicines control laboratories, from 11 countries participated in the collaborative Part 2 study, each testing 6 different C. septicum toxins and 6 C. septicum toxoids. Improved repeatability and reproducibility were observed for the optimised assays. The results of this study confirm the suitability of these assays for in-process control of C. septicum vaccines, with better repeatability and reproducibility than their in vivo equivalents. It is expected that, with appropriate minor changes and the use of relevant reagents, these optimised in vitro assays could be used not only for the assessment of C. septicum toxins and toxoids but for all cytotoxin-based clostridial antigens. The development and implementation of such in vitro assays would offer a great opportunity to significantly reduce animal usage, shorten the duration of QC test procedures and increase the precision of toxicity and antigenicity assays in clostridial veterinary vaccine in-process control. This would also provide more accurate and reproducible dosing of antigens in the final vaccine products, help to promote compendial acceptance and to proffer a basis for improved international harmonisation across this area of product testing.


Assuntos
Clostridium septicum , Animais , Antígenos de Bactérias , Linhagem Celular , Camundongos , Reprodutibilidade dos Testes , Toxoide Tetânico
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