Clostridium perfringens phospholipase C, an archetypal bacterial virulence factor, induces the formation of extracellular traps by human neutrophils.

Neutrophil extracellular traps (NETs) are networks of DNA and various microbicidal proteins released to kill invading microorganisms and prevent their dissemination. However, a NETs excess is detrimental to the host and involved in the pathogenesis of various inflammatory and immunothrombotic diseases. Clostridium perfringens is a widely distributed pathogen associated with several animal and human diseases, that produces many exotoxins, including the phospholipase C (CpPLC), the main virulence factor in gas gangrene. During this disease, CpPLC generates the formation of neutrophil/platelet aggregates within the vasculature, favoring an anaerobic environment for C. perfringens growth. This work demonstrates that CpPLC induces NETosis in human neutrophils. Antibodies against CpPLC completely abrogate the NETosis-inducing activity of recombinant CpPLC and C. perfringens secretome. CpPLC induces suicidal NETosis through a mechanism that requires calcium release from inositol trisphosphate receptor (IP3) sensitive stores, activation of protein kinase C (PKC), and the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathways, as well as the production of reactive oxygen species (ROS) by the metabolism of arachidonic acid. Proteomic analysis of the C. perfringens secretome identified 40 proteins, including a DNAse and two 5´-nucleotidases homologous to virulence factors that could be relevant in evading NETs. We suggested that in gas gangrene this pathogen benefits from having access to the metabolic resources of the tissue injured by a dysregulated intravascular NETosis and then escapes and spreads to deeper tissues. Understanding the role of NETs in gas gangrene could help develop novel therapeutic strategies to reduce mortality, improve muscle regeneration, and prevent deleterious patient outcomes.

Primary abdominal gas gangrene: a report of two autopsy cases

Primary hepatic gas gangrene is a form of primary abdominal gas gangrene. The condition is caused by Clostridium perfringens, other clostridia, and non-clostridia bacterial species producing gas. Unlike classical gas gangrene or myonecrosis, the disease develops without a wound or a port of entry. Instead, gas-producing bacteria in the gastrointestinal tract colonize an underlying pathological process with foci of necrosis, producing excessive gas and spreading hematogenously to other organs. Herein we present two autopsy cases of primary hepatic gas gangrene diagnosed on autopsy, with the gross and histological changes that can be considered specific for this rare condition. Both patients had severe underlying liver disease-prone for this entity development. The gross changes in the cases are postmortem subcutaneous emphysema, skin bullae with pooled blood, pneumothorax, pneumoabdomen, abundant gas in the circulatory system, porous structure of the internal organs (tissue gas bubbles), and advanced tissue lysis, not corresponding to the post mortem time. Histology showed optically empty areas of varying size in the internal organs, which weave the structure of the organs and rod-shaped bacteria with scarcity or complete absence of inflammatory reaction.

Clostridium perfringens α and ß recombinant toxoids in equine immunization / Toxóides recombinantes α e ß de Clostridium perfringens na imunização de equinos

Clostridium perfringens is considered one of the main causative agents of superacute enterocolitis, usually fatal in the equine species, due to the action of the ß toxin, and is responsible for causing severe myonecrosis, by the action of the α toxin. The great importance of this agent in the equine economy is due to high mortality and lack of vaccines, which are the main form of prevention, which guarantee the immunization of this animal species. The aim of this study was to evaluate three different concentrations (100, 200 and 400µg) of C. perfringens α and ß recombinant toxoids in equine immunization and to compare with a group vaccinated with a commercial toxoid. The commercial vaccine was not able to stimulate an immune response and the recombinant vaccine was able to induce satisfactory humoral immune response in vaccinated horses, proving to be an alternative prophylactic for C. perfringens infection.(AU)

Clostridium perfringens é considerado um dos principais agentes causadores de enterocolites superagudas, geralmente fatais na espécie equina, devido à ação da toxina ß, além de ser responsável por causar quadros graves de mionecrose, pela ação da toxina α. A grande importância desses agentes na equinocultura, deve-se a elevada mortalidade e a inexistência de vacinas, principal forma de prevenção, que garantam a imunização dessa espécie animal. O objetivo deste trabalho foi avaliar três diferentes concentrações (100, 200 e 400µg) dos toxóides recombinantes α e ß de C. perfringens na imunização de equinos, bem como comparar com um grupo vacinado com um toxóide comercial. A vacina comercial não se mostrou capaz de estimular uma resposta imune e a vacina recombinante foi capaz de induzir resposta imune humoral satisfatória em equinos vacinados, provando ser uma alternativa profilática para infecção por C. Perfringens.(AU)

Clostridium perfringens α and ß recombinant toxoids in equine immunization / Toxóides recombinantes α e ß de Clostridium perfringens na imunização de equinos

Clostridium perfringens is considered one of the main causative agents of superacute enterocolitis, usually fatal in the equine species, due to the action of the ß toxin, and is responsible for causing severe myonecrosis, by the action of the α toxin. The great importance of this agent in the equine economy is due to high mortality and lack of vaccines, which are the main form of prevention, which guarantee the immunization of this animal species. The aim of this study was to evaluate three different concentrations (100, 200 and 400µg) of C. perfringens α and ß recombinant toxoids in equine immunization and to compare with a group vaccinated with a commercial toxoid. The commercial vaccine was not able to stimulate an immune response and the recombinant vaccine was able to induce satisfactory humoral immune response in vaccinated horses, proving to be an alternative prophylactic for C. perfringens infection.(AU)

Clostridium perfringens é considerado um dos principais agentes causadores de enterocolites superagudas, geralmente fatais na espécie equina, devido à ação da toxina ß, além de ser responsável por causar quadros graves de mionecrose, pela ação da toxina α. A grande importância desses agentes na equinocultura, deve-se a elevada mortalidade e a inexistência de vacinas, principal forma de prevenção, que garantam a imunização dessa espécie animal. O objetivo deste trabalho foi avaliar três diferentes concentrações (100, 200 e 400µg) dos toxóides recombinantes α e ß de C. perfringens na imunização de equinos, bem como comparar com um grupo vacinado com um toxóide comercial. A vacina comercial não se mostrou capaz de estimular uma resposta imune e a vacina recombinante foi capaz de induzir resposta imune humoral satisfatória em equinos vacinados, provando ser uma alternativa profilática para infecção por C. Perfringens.(AU)

Clostridial diseases diagnosed in cattle from the South of Rio Grande do Sul, Brazil. A forty-year survey (1978-2018) and a brief review of the literature / Clostridioses diagnosticadas em bovinos no sul do Rio Grande do Sul. Uma pesquisa de quarenta anos (1978-2018) e breve revisão da literatura

Clostridial diseases are important causes of livestock losses in the southern Rio Grande do Sul. Since 1978 annual surveys conducted at the "Laboratório Regional de Diagnóstico" of the "Universidade Federal de Pelotas" (LRD-UFPel) have shown that clostridial diseases represent 10.40% of the bacterial diseases diagnosed in cattle and 1.65% of all diseases diagnosis in cattle over a 40-year period. The purpose of this study is to review the clinical, epidemiological and pathological aspects of the clostridial diseases diagnosed in cattle from January 1978 to December 2018 at the LRD-UFPel in the hopes that it will constitute a useful guide for field veterinary practitioners and interested farmers. We assessed and review the necropsy protocols of 6,736 cattle; these necropsies were performed either by LRD-UFPel faculty or by field veterinary practitioners; 111 outbreaks (1.65%) were diagnosed as clostridial disease, distributed as follows: 35 outbreaks of tetanus, 34 of blackleg, 23 of bacillary hemoglobinuria, 11 of malignant edema (gas gangrene), and eight of botulism. Approximately 904, from a total of 42,480 cattle at risk, died in these outbreaks.(AU)

Clostridioses são doenças produzidas por alguma das espécies do gênero Clostridium e são importantes causas de perdas pecuárias no sul do Rio Grande do Sul. Pesquisas anuais realizadas no Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD-UFPel) desde 1978 demonstraram que as clostridioses representaram 11,1% das doenças bacterianas diagnosticadas em bovinos e 1,65% de todos os diagnósticos de doenças em bovinos ao longo de 40 anos. O objetivo deste estudo é revisar os aspectos clínicos, epidemiológicos e patológicos das clostridioses diagnosticadas de janeiro de 1978 a dezembro de 2018, pelo LRD/UFPel com a intenção de que esse trabalho possa servir de guia útil para os veterinários de campo e fazendeiros interessados. Foram avaliados e revisados os protocolos de necropsia de 6.736 bovinos; essas necropsias foram realizadas pelo pessoal do LRD/UFPel ou por veterinários de campo. Cento e quatro (1,16%) casos foram diagnosticados como clostridioses, distribuídos da seguinte forma: 35 surtos de tétano, 34 de carbúnculo sintomático, 23 de hemoglobinúria bacilar, 11 de edema maligno (gangrena gasosa) e oito de botulismo. Aproximadamente 904, de um total de 42.480 bovinos sob-risco, morreram nesses surtos.(AU)

Clostridial diseases diagnosed in cattle from the South of Rio Grande do Sul, Brazil. A forty-year survey (1978-2018) and a brief review of the literature / Clostridioses diagnosticadas em bovinos no sul do Rio Grande do Sul. Uma pesquisa de quarenta anos (1978-2018) e breve revisão da literatura

Clostridial diseases are important causes of livestock losses in the southern Rio Grande do Sul. Since 1978 annual surveys conducted at the "Laboratório Regional de Diagnóstico" of the "Universidade Federal de Pelotas" (LRD-UFPel) have shown that clostridial diseases represent 10.40% of the bacterial diseases diagnosed in cattle and 1.65% of all diseases diagnosis in cattle over a 40-year period. The purpose of this study is to review the clinical, epidemiological and pathological aspects of the clostridial diseases diagnosed in cattle from January 1978 to December 2018 at the LRD-UFPel in the hopes that it will constitute a useful guide for field veterinary practitioners and interested farmers. We assessed and review the necropsy protocols of 6,736 cattle; these necropsies were performed either by LRD-UFPel faculty or by field veterinary practitioners; 111 outbreaks (1.65%) were diagnosed as clostridial disease, distributed as follows: 35 outbreaks of tetanus, 34 of blackleg, 23 of bacillary hemoglobinuria, 11 of malignant edema (gas gangrene), and eight of botulism. Approximately 904, from a total of 42,480 cattle at risk, died in these outbreaks.(AU)

Clostridioses são doenças produzidas por alguma das espécies do gênero Clostridium e são importantes causas de perdas pecuárias no sul do Rio Grande do Sul. Pesquisas anuais realizadas no Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD-UFPel) desde 1978 demonstraram que as clostridioses representaram 11,1% das doenças bacterianas diagnosticadas em bovinos e 1,65% de todos os diagnósticos de doenças em bovinos ao longo de 40 anos. O objetivo deste estudo é revisar os aspectos clínicos, epidemiológicos e patológicos das clostridioses diagnosticadas de janeiro de 1978 a dezembro de 2018, pelo LRD/UFPel com a intenção de que esse trabalho possa servir de guia útil para os veterinários de campo e fazendeiros interessados. Foram avaliados e revisados os protocolos de necropsia de 6.736 bovinos; essas necropsias foram realizadas pelo pessoal do LRD/UFPel ou por veterinários de campo. Cento e quatro (1,16%) casos foram diagnosticados como clostridioses, distribuídos da seguinte forma: 35 surtos de tétano, 34 de carbúnculo sintomático, 23 de hemoglobinúria bacilar, 11 de edema maligno (gangrena gasosa) e oito de botulismo. Aproximadamente 904, de um total de 42.480 bovinos sob-risco, morreram nesses surtos.(AU)

Deficient Skeletal Muscle Regeneration after Injury Induced by a Clostridium perfringens Strain Associated with Gas Gangrene.

Gas gangrene, or clostridial myonecrosis, is usually caused by Clostridium perfringens and may occur spontaneously in association with diabetes mellitus, peripheral vascular disease, or some malignancies but more often after contamination of a deep surgical or traumatic lesion. If not controlled, clostridial myonecrosis results in multiorgan failure, shock, and death, but very little is known about the muscle regeneration process that follows myonecrosis when the infection is controlled. In this study, we characterized the muscle regeneration process after myonecrosis caused in a murine experimental infection with a sublethal inoculum of C. perfringens vegetative cells. The results show that myonecrosis occurs concomitantly with significant vascular injury, which limits the migration of inflammatory cells. A significant increase in cytokines that promote inflammation explains the presence of an inflammatory infiltrate; however, impaired interferon gamma (IFN-γ) expression, a reduced number of M1 macrophages, deficient phagocytic activity, and a prolongation of the permanence of inflammatory cells lead to deficient muscle regeneration. The expression of transforming growth factor ß1 (TGF-ß1) agrees with the consequent accumulation of collagen in the muscle, i.e., fibrosis observed 30 days after infection. These results provide new information on the pathogenesis of gas gangrene caused by C. perfringens, shed light on the basis of the deficient muscle regenerative activity, and may open new perspectives for the development of novel therapies for patients suffering from this disease.

Infección mortal por Clostridium perfringens con hemólisis tras quimioterapia en un adolescente / A fatal Clostridium perfringens infection with hemolysis after chemotherapy in an adolescent

La gangrena gaseosa, o mionecrosis clostridial, es una de las enfermedades infecciosas más graves, y se caracteriza por la rápida y progresiva destrucción de los tejidos blandos profundos y la producción de gas dentro de los tejidos. Presentamos un caso de gangrena gaseosa espontánea mortal causada por Clostridium perfringens en un paciente con leucemia linfocítica aguda durante la fase de quimioterapia de inducción de la remisión.

Gas gangrene, clostridial myonecrosis, is one of the most serious infectious diseases, characterized by rapidly progressive destruction of deep soft tissues and production of gas within the tissues. We presented a case of fatal spontaneous gas gangrene due to Clostridium perfringens in a patient with acute lymphoblastic leukemia during remission induction chemotherapy phase.

A fatal Clostridium perfringens infection with hemolysis after chemotherapy in an adolescent. / Infección mortal por Clostridium perfringens con hemólisis tras quimioterapia en un adolescente.

Gas gangrene, clostridial myonecrosis, is one of the most serious infectious diseases, characterized by rapidly progressive destruction of deep soft tissues and production of gas within the tissues. We presented a case of fatal spontaneous gas gangrene due to Clostridium perfringens in a patient with acute lymphoblastic leukemia during remission induction chemotherapy phase.

La gangrena gaseosa, o mionecrosis clostridial, es una de las enfermedades infecciosas más graves, y se caracteriza por la rápida y progresiva destrucción de los tejidos blandos profundos y la producción de gas dentro de los tejidos. Presentamos un caso de gangrena gaseosa espontánea mortal causada por Clostridium perfringens en un paciente con leucemia linfocítica aguda durante la fase de quimioterapia de inducción de la remisión.

A retrospective study on the diagnosis of clostridial myonecrosis in ruminants in Brazil / Estudo retrospectivo sobre o diagnóstico de mionecroses clostridiais em ruminantes no Brasil

A standardized immunochemistry method for the diagnosis of clostridial myonecrosis was applied to 38 formalized tissue samples from ruminants with clinical and post mortem history suggestive of blackleg or gas gangrene. The diagnosis of clostridial myonecrosis was confirmed in 37 out of 38 (97.4%) samples tested. Clostridium chauvoei and Clostridium perfringens type A were the most common agents found alone, being detected in ten (26.3%) and six (15.8%) samples, respectively. The other cases showed an association of two or three clostridia, with C. perfringens type A detected in 11 (29%) cases. Based on the findings of the present study, polyvalent vaccines against clostridial infections of animals incorporating C. perfringens would be more adequate for preventative purposes in the endemic areas.

Imuno-istoquímica padronizada para avaliar o diagnóstico etiológico de mionecrose por agentes do gênero Clostridium foi utilizada em 38 tecidos formalizados de ruminantes com suspeita clínica e macroscópica, além de histopatologia compatível com carbúnculo sintomático ou gangrena gasosa. O diagnóstico de mionecrose foi confirmado em 37 das 38 (97,4%) amostras avaliadas. Clostridium chauvoei e Clostridium perfringens tipo A foram os únicos agentes encontrados sozinhos, sendo detectados em dez (26,3%) e seis (15,8%) amostras, respectivamente. Os outros casos foram causados por combinações de dois ou mais agentes, sendo que C. perfringens type A foi detectado em dez (29,9%) dessas amostras. Baseado nos resultados obtidos, sugere-se que vacinas polivalentes contendo C. perfringens seriam mais adequadas para prevenção de mionecrose causada por clostrídios.

A retrospective study on the diagnosis of clostridial myonecrosis in ruminants in Brazil / Estudo retrospectivo sobre o diagnóstico de mionecroses clostridiais em ruminantes no Brasil

A standardized immunochemistry method for the diagnosis of clostridial myonecrosis was applied to 38 formalized tissue samples from ruminants with clinical and post mortem history suggestive of blackleg or gas gangrene. The diagnosis of clostridial myonecrosis was confirmed in 37 out of 38 (97.4%) samples tested. Clostridium chauvoei and Clostridium perfringens type A were the most common agents found alone, being detected in ten (26.3%) and six (15.8%) samples, respectively. The other cases showed an association of two or three clostridia, with C. perfringens type A detected in 11 (29%) cases. Based on the findings of the present study, polyvalent vaccines against clostridial infections of animals incorporating C. perfringens would be more adequate for preventative purposes in the endemic areas.(AU)

Imuno-istoquímica padronizada para avaliar o diagnóstico etiológico de mionecrose por agentes do gênero Clostridium foi utilizada em 38 tecidos formalizados de ruminantes com suspeita clínica e macroscópica, além de histopatologia compatível com carbúnculo sintomático ou gangrena gasosa. O diagnóstico de mionecrose foi confirmado em 37 das 38 (97,4%) amostras avaliadas. Clostridium chauvoei e Clostridium perfringens tipo A foram os únicos agentes encontrados sozinhos, sendo detectados em dez (26,3%) e seis (15,8%) amostras, respectivamente. Os outros casos foram causados por combinações de dois ou mais agentes, sendo que C. perfringens type A foi detectado em dez (29,9%) dessas amostras. Baseado nos resultados obtidos, sugere-se que vacinas polivalentes contendo C. perfringens seriam mais adequadas para prevenção de mionecrose causada por clostrídios.(AU)

Gangrena gaseosa / Gangrène gazeuse / Gas gangrene

Se presenta un paciente masculino de 29 años, mestizo, recluso, quien 7 días antes de haber sido remitido al servicio de urgencias del Hospital Universitario Amalia Simoni se había inoculado, en autoagresión, heces fecales en la pierna y el muslo derechos. Refirió dolor y presentaba gran toma del estado general. A la exploración física se constató aumento de volumen generalizado del miembro inferior derecho, con zonas de eritema marcado que alternaban con áreas de necrosis que incluso afectaban el abdomen bajo, aumento de la temperatura local; a la palpación, dolor intenso con amplia zona de crepitación subcutánea, además de bulas de contenido serohemático, pútrido, de olor fétido. La radiografía reveló aumento marcado de la opacidad de las partes blandas, bandas de gas a nivel del tejido celular subcutáneo y presencia de numerosas bulas sin toma ósea. Se decidió tratamiento quirúrgico multidisciplinario que incluyó la desarticulación en guillotina del miembro inferior derecho a nivel de la cadera y toilette amplia, medidas de soporte vital, y la combinación de clindamicina, vancomicina y meronem. La gangrena gaseosa es una infección fulminante de los tejidos blandos con una mortalidad elevada; la sospecha diagnóstica y el entendimiento de la fisiopatología mejoran el pronóstico. El soporte vital, el equilibrio del medio interno, el uso de antimicrobianos de amplio espectro y un tratamiento quirúrgico agresivo, disminuyen la mortalidad(AU)

A case of a 29-year convict mestizo male patient is presented here. This patient is referred to the emergency department of Traumatology at Amalia Simoni University Hospital, seven days after having self-inoculated with stool in his right leg and thigh as self-harm. The patient complained of pain and his general was very poor. Physical examination revealed generalized increase in volume of the right lower limb, with marked erythema areas alternating with areas of necrosis that were even affecting the lower abdomen; increased local temperature, tenderness, pain with subcutaneous crepitus in wide area were found, as well as bulls serohematic bulls, putrid, foul-smelling. Radiography reveals marked increase in opacity of the soft tissues, bands of gas at the level of subcutaneous tissue and the presence of numerous bulls without bone involvement. Multidisciplinary surgical treatment was decided including the guillotine disarticulation of the right leg to hip level and wide toilette, life support, and the combination of clindamycin, vancomycin, and meronem. Gas gangrene is a fulminant soft tissue infection with high mortality; the suspected diagnosis and understanding of the pathophysiology improve prognosis. Life support, balance the internal environment, the use of broad-spectrum antimicrobials and aggressive surgical treatment, reduce mortality(AU)

Un patient âgé de 29 ans, métis, reclus, référé au service d'urgences à l'hôpital universitaire "Amalia Simoni" dû à une automutilation (inoculation de selle dans la jambe et la cuisse droites), est présenté. Il a exprimé une douleur et une sensation de mal-être. Dans l'examen physique, on a pu constater une inflammation du membre inférieur droit; des zones érythémateuses très marquées alternant avec des zones nécrosées, même arrivant à l'abdomen bas; une augmentation de la température locale; une douleur violente avec une zone de crépitements à la palpation, et des bulles à contenu séro-hématique, putréfié et fétide. La radiographie a révélé une augmentation significative de l'opacité des parties molles, des bandes gazeuses au niveau du tissu cellulaire sous-cutané, et une présence de nombreuses bulles sans prise osseuse. On a décidé un traitement chirurgical pluridisciplinaire consistant à une désarticulation en guillotine du membre inférieur droit au niveau de la hanche et un curettage profond; des soins intensifs, et une combinaison de clindamycine, vancomycine et méropénème. La gangrène gazeuse est une infection fulminante des tissus mous avec un taux de mortalité très haut. Le diagnostic suspecté et la compréhension de la physiopathologie améliorent le pronostic. Les soins intensifs, l'équilibre du milieu intérieur, l'emploi d'antimicrobiens à large spectre et un traitement chirurgical agressif font réduire le taux de mortalité(AU)

Sialidase production and genetic diversity in Clostridium perfringens type A isolated from chicken with necrotic enteritis in Brazil.

The sialidase activity and genetic diversity of 22 Clostridium perfringens strains isolated from chickens with necrotic enteritis were determined. Sialidase activity was detected in 86.4 % of the strains. All C. perfringens showed a high value of similarity (>96 %), and they were grouped into seven clusters clearly separated from the other reference bacterial strains. From these clusters four patterns were defined in accordance with their phenotypic (sialidase production and antibiotic resistance profile) and genotypic (presence of nanI and nanJ genes) characteristics. Our results showed heterogeneity among strains, but they were genotypically similar, and it is suggested further studies are needed to better understand the pathogenesis of necrotic enteritis.

Development of Clostridium septicum gas gangrene as an adverse effect of clindamycin-induced Clostridium difficile infection in a pediatric patient.

Clostridium myonecrosis or gas gangrene is a life-threatening infection characterized by either traumatic or atraumatic etiology. It has been widely described in patients with traumatic open wounds and in immunocompromised patients, including malignancy. A third source can result from natural flora in the gastrointestinal tract after bowel ischemia. This is a rare occurrence and is even less commonly described in the pediatric population. We present a pediatric patient who developed Clostridium septicum myonecrosis as an iatrogenic complication from clindamycin-induced Clostridium difficile ischemic colitis.

Infecção fulminante por Clostridium septicum: relato de caso / Fulminant Clostridium septicum infection: case report

As infecções de tecidos moles causadas por espécies de Clostridium têm sido descritos na literatura por centenas de anos. A gangrena gasosa por Clostridium continua sendo uma importante causa de morbidade e mortalidade no mundo. O objetivo deste estudo foi relatar um caso de paciente com diagnóstico de síndrome mielodisplásica, submetida à curetagem uterina e evoluindo com gangrena gasosa espontânea, 10 horas após a cirurgia.Paciente do sexo feminino, 26 anos, com história de dor em terço distal de membros inferiores, irradiando para região de fossa poplítea, com piora à palpação e movimentação dos membros, acompanhada de aumento da temperatura e volume local. Negava febre, hiperemia ou trauma local, evoluindo para choque séptico. Angiotomografia das extremidades e pelve revelou a presença de gás permeando os feixes musculares da coxa e da perna, bilateralmente. A combinação da história e exame clínico,ao estudo radiológico confirmou o diagnóstico sindrômico de gangrena gasosa espontânea. Apesar de elevado índice de suspeição melhorar os resultados clínicos, tais infecções progridem tão rapidamente que o óbito pode preceder o diagnóstico,não obstante, o reconhecimento precoce e tratamento agressivo,incluindo drenagem aberta ou percutânea. Antibióticos parenterais contra Clostrídios devem ser prontamente iniciados, bem como medidas de suporte clínico.

The soft tissue infections caused by Clostridium species have been described in the literature for hundreds of years. The gas gangrene due to Clostridium remains an important cause of morbidity and mortality worldwide. The aim of this study was to report a patient diagnosed with myelodysplastic syndrome who underwent curettage, evolving with spontaneous gas gangrene, 10 hours after surgery. Female patient, 26 years, with pain in the distal third of the lower limbs, radiating to the popliteal fossa region, which worsened on palpation and movement of limbs, and accompanied by an increase in temperature and local volume. She denied fever, redness or local trauma, and progressed to septic shock. Angiotomography of the extremities and pelvis revealed the presence of gas permeating the muscle bundles of the thigh and leg bilaterally. The combination of history and clinical examination and radiological examination confirmed the syndromic diagnosis of Spontaneous Gas Gangrene. Although a high index of suspicion may improve clinical outcomes, such infections progress so rapidly that death usually precedes the diagnosis. However, early recognition and aggressive treatment, including open or percutaneous drainage and parenteral antibiotics against Clostridia should be promptly initiated, along with clinical support.

Gangrena gaseosa de la mama / Gas gangrene of the breast

La gangrena gaseosa de la mama es una enfermedad rara y potencialmente mortal descrita como consecuencia de un traumatismo, por complicaciones infecciosas de la cirugía o por una trombosis venosa. También se ha relacionado ocasionalmente con otras causas tales como la diabetes mellitus, el envenenamiento con monóxido de carbono o la cirugía plástica. Presentamos un caso de gangrena gaseosa de mama en una mujer diabética de 74 años. Esta rara infección representa una emergencia médico-quirúrgica(AU)

Gas gangrene of the breast is a rare and potentially lethal disease following trauma, as a result of infectious complications from surgery or venous thrombosis. Other rare etiologies, such as diabetes mellitus, carbon monoxide poisoning, and plastic surgery, have also been reported as related to this illness. A case of gas gangrene of the breast found in a 74-year-old diabetic woman was presented in this paper. This rare infection is a medical and surgical emergency situation(AU)

Myonecrosis by Clostridium septicum in a dog, diagnosed by a new multiplex-PCR.

Clostridial myositis is an acute, generally fatal toxemia that is considered to be rare in pet animals. The present report describes an unusual canine clostridial myositis that was diagnosed by a new multiplex-PCR (mPCR) designed for simultaneous identification of Clostridium sordellii, Clostridium septicum, Clostridium perfringens type A, Clostridium chauvoei, and Clostridium novyi type A. A ten-month-old male Rottweiler dog, that had displayed lameness and swelling of the left limb for 12 h, was admitted to a veterinary hospital. The animal was weak, dyspneic and hyperthermic, and a clinical examination indicated the presence of gas and edema in the limb. Despite emergency treatment, the animal died in only a few minutes. Samples of muscular tissue from the necrotic area were aseptically collected and plated onto defibrinated sheep blood agar (5%) in anaerobic conditions. Colonies suggestive of Clostridium spp. were submitted to testing by multiplex-PCR. Impression smears of the tissues, visualized with Gram and also with panoptic stains, revealed long rod-shaped organisms, and specimens also tested positive using the fluorescent antibody technique (FAT). The FAT and mPCR tests enabled a diagnosis of C. septicum myonecrosis in the dog.

Reactive oxygen species and the MEK/ERK pathway are involved in the toxicity of clostridium perfringens α-toxin, a prototype bacterial phospholipase C.

Clostridium perfringens, the most broadly distributed pathogen in nature, produces a prototype phospholipase C, also called α-toxin, which plays a key role in the pathogenesis of gas gangrene. α-Toxin causes plasma membrane disruption at high concentrations, but the role of intracellular mediators in its toxicity at low concentrations is unknown. This work demonstrates that α-toxin causes oxidative stress and activates the MEK/ERK pathway in cultured cells and furthermore provides compelling evidence that O(2)(-.), hydrogen peroxide, and the OH(.) radical are involved in its cytotoxic and myotoxic effects. The data show that antioxidants and MEK1 inhibitors reduce the cytotoxic and myotoxic effects of α-toxin and demonstrate that edaravone, a clinically used hydroxyl radical trap, reduces the myonecrosis and the mortality caused by an experimental infection with C. perfringens in a murine model of gas gangrene. This knowledge provides new insights for the development of novel therapies to reduce tissue damage during clostridial myonecrosis.

Sugar inhibits the production of the toxins that trigger clostridial gas gangrene.

Histotoxic strains of Clostridium perfringens cause human gas gangrene, a devastating infection during which potent tissue-degrading toxins are produced and secreted. Although this pathogen only grows in anaerobic-nutrient-rich habitats such as deep wounds, very little is known regarding how nutritional signals influence gas gangrene-related toxin production. We hypothesize that sugars, which have been used throughout history to prevent wound infection, may represent a nutritional signal against gas gangrene development. Here we demonstrate, for the first time, that sugars (sucrose, glucose) inhibited the production of the main protein toxins, PLC (alpha-toxin) and PFO (theta-toxin), responsible for the onset and progression of gas gangrene. Transcription analysis experiments using plc-gusA and pfoA-gusA reporter fusions as well as RT-PCR analysis of mRNA transcripts confirmed that sugar represses plc and pfoA expression. In contrast an isogenic C. perfringens strain that is defective in CcpA, the master transcription factor involved in carbon catabolite response, was completely resistant to the sugar-mediated inhibition of PLC and PFO toxin production. Furthermore, the production of PLC and PFO toxins in the ccpA mutant strain was several-fold higher than the toxin production found in the wild type strain. Therefore, CcpA is the primary or unique regulatory protein responsible for the carbon catabolite (sugar) repression of toxin production of this pathogen. The present results are analyzed in the context of the role of CcpA for the development and aggressiveness of clostridial gas gangrene and the well-known, although poorly understood, anti-infective and wound healing effects of sugars and related substances.

Endogenous gas gangrene after laparoscopic cholecystectomy.

Clostridial gas gangrene of the abdominal wall is rare, and it is usually associated with organ perforation, immunosuppression or gastrointestinal malignancies. In this paper we present a case of fulminant, endogenous gas gangrene in a 58-year old diabetic female with arterial hypertension and atherosclerosis, following uneventful laparoscopic cholecystectomy. She developed gas gangrene of the abdominal wall 12-hours after cholecystectomy and died 24-hours after the onset of the first symptoms, in spite of treatment.