Myonecrosis Research Articles

A case of intrathoracic gas gangrene with septic shock

A case of intrathoracic gas gangrene with septic shock

Treatment for the Case of Gas Gangrene Cause of Retroperitoneal Rupture of Sigmoid Colon Cancer

Treatment for the Case of Gas Gangrene Cause of Retroperitoneal Rupture of Sigmoid Colon Cancer

Evaluation of laboratory risk indicator for necrotizing fasciitis (Lrinec) scoring system for diagnosis of necrotizing fasciitis in patients presenting with soft tissue infection

Necrotizing soft tissue infection represents a diverse process; the term itself encompasses a continuum ranging from pyoderma to life threatening infections (clostridial gas gangrene with myonecrosis, anaerobic cellulitis, and severe, necrotizing vibrio infections). These can occur in any anatomical area but the commonest site is the extremities. Necrotizing fasciitis is often underestimated because of the lack of specific clinical findings in the initial stages of the disease. The paucity of specific cutaneous signs to distinguish necrotizing fasciitis from other soft tissue infections such as cellulitis makes the diagnosis extremely difficult. The first and most important consideration for an accurate, prompt diagnosis is to have a high index of suspicion. It has been shown by numerous studies in the past that early recognition and surgical intervention at the earliest is the sole factor in preventing the morbidity and mortality in patients with necrotizing fasciitis [1-3]. So a scoring system which is easy to follow and cost effective with high positive and negative predictive value is required. One such scoring system is the LRINEC scoring system devised by Wong et al [4] in 2005 which claims to have a positive predictive value of 92.0% and negative predictive value of 96.0%. The mortality in necrotizing fasciitis is as high as 34%. [5] We evaluated LRINEC scoring system in patients presenting with symptoms and signs suggestive of soft tissue infection that progresses to necrotizing fasciitis in Sri Ramachandra Medical College and Hospital, Porur, Chennai over a period of two years.

Spontaneous Non-Traumatic Clostridium perfringens Sepsis.

Clostridium species are gram-positive, spore-forming, anaerobic rods normally found in the soil and gastrointestinal tract of humans and animals. Spontaneous sepsis due to C. perfringens is not caused by injury, which sets it apart from the classical gas gangrene that typically follows trauma. Spontaneous C. perfringens sepsis often develops as a rapidly progressive intravascular hemolysis and metabolic acidosis, with high mortality rates of over 70% with standard intensive care. In such cases, alpha toxin secreted by C. perfringens is considered the main toxin responsible for intravascular hemolysis, disseminated intravascular coagulopathy, and multiple organ failure. Theta-toxin causes a cytokine cascade, which results in peripheral vasodilation similar to that seen in septic shock. For C. perfringens infections, antibiotics, such as high-dose penicillin, and surgical drainage as early as possible are the principal treatments of choice. However, considering the current mortality rate of sepsis, outcomes have not improved with the current standard treatment for C. perfringens infections. Monoclonal antibody against theta toxin in combination with gas gangrene antitoxin presents a promising therapeutic option.

Immunization of rabbits with recombinant Clostridium perfringens alpha toxins CPA-C and CTB-CPA-C in a bicistronic design expression system confers strong protection against challenge

The Clostridium perfringens alpha toxin (CPA), encoded by the plc gene, is the causative pathogen of gas gangrene, which is a lethal infection. In this study, we used an E. coli system for the efficient production of recombinant proteins and developed a bicistronic design (BCD) expression construct consisting of two copies of the C-terminal (247–370) domain of the alpha toxin (CPA-C) in the first cistron, followed by Cholera Toxin B (CTB) linked with another two copies of CPA-C in the second cistron that is controlled by a single promoter. Rabbits were immunized twice with purified proteins (rCPA-C rCTB-CPA-C) produced in the BCD expression system, with an inactivated recombinant E. coli vaccine (RE), C. perfringens formaldehyde-inactivated alpha toxoid (FA-CPA) and C. perfringensl-lysine/formaldehyde alpha toxoid (LF-CPA) vaccines. Following the second vaccination, 0.1 mL of pooled sera of the RE-vaccinated rabbits could neutralize 12× mouse LD100 (100% lethal dose) of CPA, while that of the rCPA-C rCTB-CPA-C-vaccinated rabbits could neutralize 6× mouse LD100 of CPA. Antibody titers against CPA were also assessed by ELISA, reaching titers as high as 1:2048000 in the RE group; this was significantly higher compared to the C. perfringens alpha toxoid vaccinated groups (FA-CPA and LF-CPA). Rabbits from all vaccinated groups were completely protected from a 2× rabbit LD100 of CPA challenge. These results demonstrate that the recombinant proteins are able to induce a strong immune responses, indicating that they may be potentially utilized as targets for novel vaccines specifically against the C. perfringens alpha toxin.

Thermophile Lytic Enzyme Fusion Proteins that Target Clostridium perfringens.

Clostridium perfringens is a bacterial pathogen that causes necrotic enteritis in poultry and livestock, and is a source of food poisoning and gas gangrene in humans. As the agriculture industry eliminates the use of antibiotics in animal feed, alternatives to antibiotics will be needed. Bacteriophage endolysins are enzymes used by the virus to burst their bacterial host, releasing bacteriophage particles. This type of enzyme represents a potential replacement for antibiotics controlling C. perfringens. As animal feed is often heat-treated during production of feed pellets, thermostable enzymes would be preferred for use in feed. To create thermostable endolysins that target C. perfringens, thermophile endolysin catalytic domains were fused to cell wall binding domains from different C. perfringens prophage endolysins. Three thermostable catalytic domains were used, two from prophage endolysins from two Geobacillus strains, and a third endolysin from the deep-sea thermophilic bacteriophage Geobacillus virus E2 (GVE2). These domains harbor predicted L-alanine-amidase, glucosaminidase, and L-alanine-amidase activities, respectively and degrade the peptidoglycan of the bacterial cell wall. The cell wall binding domains were from C. perfringens prophage endolysins (Phage LYtic enzymes; Ply): PlyCP18, PlyCP10, PlyCP33, PlyCP41, and PlyCP26F. The resulting fifteen chimeric proteins were more thermostable than the native C. perfringens endolysins, and killed swine and poultry disease-associated strains of C. perfringens.

A deadly villain tamed – two cases of spontaneous gas gangrene

A deadly villain tamed – two cases of spontaneous gas gangrene

Inflammasome Activation Induced by Perfringolysin O of Clostridium perfringens and Its Involvement in the Progression of Gas Gangrene.

Clostridium perfringens (C. perfringens) is Gram-positive anaerobic, spore-forming rod-shaped bacterial pathogen that is widely distributed in nature. This bacterium is known as the causative agent of a foodborne illness and of gas gangrene. While the major virulence factors are the α-toxin and perfringolysin O (PFO) produced by type A strains of C. perfringens, the precise mechanisms of how these toxins induce the development of gas gangrene are still not well understood. In this study, we analyzed the host responses to these toxins, including inflammasome activation, using mouse bone marrow-derived macrophages (BMDMs). Our results demonstrated, for the first time, that C. perfringens triggers the activation of caspase-1 and release of IL-1β through PFO-mediated inflammasome activation via a receptor of the Nod-like receptor (NLR) family, pyrin-domain containing 3 protein (NLRP3). The PFO-mediated inflammasome activation was not induced in the cultured myocytes. We further analyzed the functional roles of the toxins in inducing myonecrosis in a mouse model of gas gangrene. Although the myonecrosis was found to be largely dependent on the α-toxin, PFO also induced myonecrosis to a lesser extent, again through the mediation of NLRP3. These results suggest that C. perfringens triggers inflammatory responses via PFO-mediated inflammasome activation via NLRP3, and that this axis contributes in part to the progression of gas gangrene. Our findings provide a novel insight into the molecular mechanisms underlying the pathogenesis of gas gangrene caused by C. perfringens.

Gas gangrene as a surgical emergency - own experience.

In this paper the authors would like to present a correct procedure in both surgical and hyperbaric treatment of patients with gas gangrene admitted to a surgical department during ER. Gas gangrene is not very common these days, but when it comes to dealing with gangrenous infection in the emergency it is quite likely to make errors in both diagnostic and therapeutic manners. When there is a gas gangrene in a patient at the emergency time plays crucial role and the proper application of procedures is vital for the patient's survival. 10 cases made the study group here, all of them were patients diagnosed and treated surgically due to gas gangrene. As shown here, It is important to perform a revision of surgical wounds after few hours since primary surgery and to begin hyperbaric treatment as quickly as possible. The findings and suggestions included in this study are supported by own experience of The 2nd Department of General and Gastrointestinal Surgery of Medical University in Białystok, Poland.

Clostridium sordellii–associated gas gangrene in 8 horses, 1998–2019

Gas gangrene occurs in several animal species and is caused by one or more clostridial species. In horses, the disease is most often caused by Clostridium perfringens type A. Although Clostridium sordellii has been associated with gas gangrene in ruminants and humans, cases of the disease associated with this microorganism have not been described in horses, to our knowledge. We report herein 8 cases of gas gangrene caused by C. sordellii in horses. These cases were characterized by myonecrosis and cellulitis, associated with systemic changes suggestive of toxic shock. The diagnosis was confirmed by gross and microscopic changes combined with anaerobic culture, fluorescent antibody test, immunohistochemistry, and/or PCR. The predisposing factor in these cases was an injection or a traumatic skin injury. C. sordellii should be considered as a possible etiologic agent in cases of gas gangrene in horses.

CN97 - Catheter related necrotizing fascitiis in haematological patients: Case report and implications for nursing

BackgroundNecrotizing fasciitis (NF) is a live-treating acute skin infection of soft tissues and muscles, extended from a trivial skin lesion, with rapid progression to necrosis. It is relatively uncommon and has a high mortality rate (∼32.2%) approaching 100% without treatment. Most cases present an anaerobic bacterium that produce gas, accumulated in the soft tissue spaces giving the characteristic image of gas gangrene on X rays (1). Site inspection reveals inflammation, oedema, and discoloration or gangrene and anaesthesia. A distinguishing clinical feature is the induration of the subcutaneous tissues (2). Early diagnosis is mandatory. Delay is associated with more extensive surgery and higher rates of amputation and mortality (1). Therapy includes radical surgical debridement with empirical broad-spectrum antibiotic coverage (2,3). Immunosuppressed patients or suffering from haematological malignancies are particularly at risk presenting an atypical etiopathology (3). MethodsTwo cases were retrospectively reviewed through medical history records to determine possible nursing implications to prevent or detect earlier cases in the future. ResultsPatient A: 53 year old woman being treated for Acute Myeloid Leukaemia (AML) with grade 4 neutropenia. She referred pain in her catheter site and presented fever and hypotension. After some days NF was diagnosed requiring 3 surgical interventions. Pseudomonas Aeruginosa was isolated in blood cultures. Patient B: 71 year old woman under treatment for AML with grade 3 neutropenia. NF in her Peripheral Insertion Central Catheter site was diagnosed. She presented no symthoms the days before but fever in the diagnosis. She required 2 surgical interventions. Klebsiella oxytoca and Enterobacter cloacae were isolated in blood cultures. Intensive care admission and longer hospitalization was required in both cases. NF was controlled but they had long term consequences (loss of mobility, paresthesia or pain). ConclusionsFN is a rare potentially lethal infection in neutropenic patients. Oncology Nurses must be aware of this complication and patient implications in order to detect it earlier. Prompt diagnosis is crucial to prevent major surgical trauma, mortality and long-term morbidity. Legal entity responsible for the studyHosptial Clínic de Barcelona. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Vaccine Production to Protect Animals Against Pathogenic Clostridia.

Clostridium is a broad genus of anaerobic, spore-forming, rod-shaped, Gram-positive bacteria that can be found in different environments all around the world. The genus includes human and animal pathogens that produce potent exotoxins that cause rapid and potentially fatal diseases responsible for countless human casualties and billion-dollar annual loss to the agricultural sector. Diseases include botulism, tetanus, enterotoxemia, gas gangrene, necrotic enteritis, pseudomembranous colitis, blackleg, and black disease, which are caused by pathogenic Clostridium. Due to their ability to sporulate, they cannot be eradicated from the environment. As such, immunization with toxoid or bacterin-toxoid vaccines is the only protective method against infection. Toxins recovered from Clostridium cultures are inactivated to form toxoids, which are then formulated into multivalent vaccines. This review discusses the toxins, diseases, and toxoid production processes of the most common pathogenic Clostridium species, including Clostridium botulinum, Clostridium tetani, Clostridium perfringens, Clostridium chauvoei, Clostridium septicum, Clostridium novyi and Clostridium hemolyticum.

Hematogenous infection of total hip arthroplasty due to clostridium perfringens: a case report

A case report of periprosthetic hip clostridium perfringens infection 13 years after total hip arthroplasty, the patient had hip pain with fever for one week. Physical examination and imaging examination confirmed the periprosthetic joint infection. The pathogenic bacterium was clostridium perfringens according to bacterial culture, and the pathogenic bacterium of clostridium perfringens was suspected relating to the gallbladder disease in this patient. Considering such periprosthetic joint infection was early stage hematogenous periprosthetic joint infection, treatment of debridement, retention of the prosthesis, irrigating, and indwelling drainage tube were conducted. By reviewing literature about periprosthetic clostridium perfringens infection, only seven reports of periprosthetic joint infection were caused by clostridium perfringens, which were all case reports. From the previous case reports and our case, we found that the infection around the prosthesis caused by clostridium perfringens was limited to the area around the joint, and prognosis of such cases may not be as severe as the natural gas gangrene which developed very rapidly, but great attention should be paid to. The hematogenous periprosthetic joint infection caused by clostridium perfringens who had gastrointestinal symptoms in the early stage should be highly suspicious of gallbladder lesions and thorough debridement, retention of the prosthesis, irrigating and indwelling drainage tube maybe a treatment method.

Granulocyte Colony-Stimulating Factor Does Not Influence Clostridium Perfringens α-Toxin-Induced Myonecrosis in Mice.

Clostridium perfringens type A causes gas gangrene characterized by myonecrosis and development of an effective therapy for treating affected patients is of clinical importance. It was recently reported that the expression of granulocyte colony-stimulating factor (G-CSF) is greatly up-regulated by C. perfringens infection. However, the role of G-CSF in C. perfringens-mediated myonecrosis is still unclear. Here, we assessed the destructive changes in C. perfringens-infected skeletal muscles and tested whether inhibition of G-CSF receptor (G-CSFR) signaling or administration of recombinant G-CSF affects the tissue injury. Severe edema, contraction of muscle fiber diameter, and increased plasma creatine kinase activity were observed in mice intramuscularly injected with C. perfringens type A, and the destructive changes were α-toxin-dependent, indicating that infection induces the destruction of skeletal muscle in an α-toxin-dependent manner. G-CSF plays important roles in the protection of tissue against damage and in the regeneration of injured tissue. However, administration of a neutralizing antibody against G-CSFR had no profound impact on the destructive changes to skeletal muscle. Moreover, administration of recombinant human G-CSF, filgrastim, imparted no inhibitory effect against the destructive changes caused by C. perfringens. Together, these results indicate that G-CSF is not beneficial for treating C. perfringens α-toxin-mediated myonecrosis, but highlight the importance of revealing the mechanism by which C. perfringens negates the protective effects of G-CSF in skeletal muscle.

Type A fulminant Clostridium perfringens sepsis indicated RBC/Hb discrepancy; a case report

BackgroundClostridium perfringens can cause various infections, including food poisoning, gas gangrene, cellulitis and fasciitis. C. perfringens septicemia is rare, but is a known cause of hemolysis by damaging red blood cell, and often proves rapidly fatal in emergency department (ED) situations.Case presentationA previously healthy 76-year-old man presented to the ED 8 h after onset of acute abdominal pain and diarrhea. Laboratory examination revealed a large discrepancy between the red blood cell count of 1.91 × 106/mm3 and the hemoglobin level of 10.3 g/dL, suggesting massive intravascular hemolysis. Computed tomography revealed liver abscesses with gas. During ED treatment, the state of the patient rapidly deteriorated and he entered cardiopulmonary arrest. Blood cultures finally identified C. perfringens.ConclusionIntravascular hemolysis and red blood cell (RBC) / hemoglobin (Hb) discrepancy in the presence of infection should prompt ED physicians to consider C. perfringens septicemia and to act quickly to provide appropriate treatment.

Vaskularizovaná fibula a šľachový transfer v komplexnej liečbe otvorenej zlomeniny predlaktia komplikovanej plynnou sneťou

Vaskularizovaná fibula a šľachový transfer v komplexnej liečbe otvorenej zlomeniny predlaktia komplikovanej plynnou sneťou

A rare case of gas under diaphragm due to spontaneous perforation of uterus due to gas gangrene of uterus with clostridium perfringens infection presenting as intestinal perforation

Uterine perforation is an uncommon, perforation due to clostridium perfringens is very rare, but potentially serious complication of uterine gangrene is due to clostridial infection, uterine manipulation, evacuation of retained products, termination of pregnancy, during coil insertion and hysteroscopic procedures. We report a 60 year old female patient presented with abdominal pain, constipation and Fever with features of septic shock. X-ray showed free gas under both domes of diaphragm. CT showed gas under diaphragm and hollow viscus perforation. This report aims to alert surgeons to the possibility that perforation of uterus due to gangrene with clostridium perfringens infection also shows air under diaphragm apart from routine causes. Correct diagnosis and treatment is essential for the survival of the patients with gas under diaphragm due to gas gangrene of uterus.

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 β1 (TGF-β1) 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.

Histotoxic Clostridial Infections.

The pathogenesis of clostridial myonecrosis or gas gangrene involves an interruption to the blood supply to the infected tissues, often via a traumatic wound, anaerobic growth of the infecting clostridial cells, the production of extracellular toxins, and toxin-mediated cell and tissue damage. This review focuses on host-pathogen interactions in Clostridium perfringens-mediated and Clostridium septicum-mediated myonecrosis. The major toxins involved are C. perfringens α-toxin, which has phospholipase C and sphingomyelinase activity, and C. septicum α-toxin, a β-pore-forming toxin that belongs to the aerolysin family. Although these toxins are cytotoxic, their effects on host cells are quite complex, with a range of intracellular cell signaling pathways induced by their action on host cell membranes.

Application of vacuum sealing drainage in limb salvage of multiple trauma patients with Gustilo type III C open fracture

Objective To investigate the safety and effectiveness of vacuum sealing drainage treatment on limb salvage in multiple trauma patients combined with Gustilo type IIIC fracture. Methods A retrospective case control study was conducted to analyze the clinical data of 102 patients diagnosed with multiple trauma combined with Gustilo type III C fracture admitted to Tongji Hospital from October 2005 to October 2015. There were 66 males and 36 females, aged 17-65 years [(34.2±10.1)years]. The injury severity score (ISS) ranged from 18 to 26 points [(19.8±3.2)points]. There were 34 patients with femur fracture, 66 with tibia/fibula fracture, 35 with femur and tibia/fibula fracture. Among the patients, 58 were treated with VSD (VSD group) and 44 were treated with routine dressing change after emergency operation (routine group). The two groups were compared for active bleeding, re-vascular exploration, osteofascial compartment syndrome, wound infection and necrosis, gas gangrene, delayed amputation, systemic inflammatory response syndrome (SIRS), sepsis, deep venous thrombosis (DVT) incidence, per capita debridement times, length of stay, skin graft/skin flap rate, fracture fixation rate, incidence of refractory wounds, incidence of nonunion, incidence of complete nerve damage, British medical research council (BMRC) score, and amputation rate/salvage rate. Results All patients were followed up for 6-14 months [(8.4±2.1)months]. There was no significant difference in limb salvage rate between the two groups after operation (P>0.05). Among the indexes of limb salvage treatment after operation, no significant differences were found between the routine group and VSD group in active bleeding, gas gangrene, re-vascular exploration and delayed amputation (P>0.05); the wound infection and necrosis rates were 32% and 15% (P<0.05); the incidence rates of osteofascial compartment syndrome were 22% and 7% (P<0.05). During the hospital stay, there were no significant differences in DVT incidence and fracture internal fixation rate between the two groups; SIRS incidence rates of routine group and VSD group were 92% and 73% (P<0.05); the incidence rates of sepsis were 28% and 10% (P<0.05); the per capita debridement times in routine group and VSD group were 4.2 times and 3.2 times, respectively (P<0.05); hospitalization durations were 42.1 days and 30.2 days (P<0.05); skin graft/skin flap rates were 69% and 46% (P<0.05). In the follow-up results, there was no significant difference in the amputation rate/salvage rate between the two groups (P<0.05). The incidence of refractory wounds was 28% in routine group and 10% in VSD group (P<0.05); the incidence of nonunion was 22% and 6% (P<0.05); the incidence of complete neurological damage was 36% and 12% (P<0.05); the excellent and good rate of BMRC score was 83% and 96% (P<0.05). Conclusions VSD technology can promote wound healing after operation, prevent complications, reduce the number of debridement operations and shorten hospital stay, significantly improving the prognosis and limb function of patients. It is a relatively safe and effective method for the treatment of multiple trauma combined with Gustilo type III C fracture. Key words: Multiple trauma; Negative-pressure wound therapy; Fractures, open; Prognosis