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Aim: Gas gangrene (GG) is a rare severe infection with a very high mortality rate mainly caused by Clostridium species. It develops suddenly, often as a complication of abdominal surgery or liver transplantation. We report a case of GG of the liver occurred after percutaneous microwave (MW) ablation of an hepatocellular carcinoma (HCC) successfully treated with percutaneous Radiofrequency ablation (RFA). Case presentation: A 76-year-old female patient was treated with MW ablation for a large HCC in the VIII segment; 2 days later she developed fever, weakness, abdominal swelling and was hospitalized with diagnosis of anaerobic liver abscess. Despite antibiotic therapy, the patient conditions worsened, and she was moved to the intensive care unit (ICU). Percutaneous drainage was attempted, but was unsuccessful. The surgeon and the anesthesiologist excluded any indication of surgical resection. We performed RFA of the GG by 3 cool-tip needles into the infected area. The procedure was well tolerated by the patient, who left the hospital for follow-up. Conclusion: Percutaneous RFA could be a valuable therapy of focal GG of the liver in patients refractory to antibiotics and when surgery and OLT are not feasible. A fast and early indication is needed in case of rapid worsening of the patient's conditions. [ABSTRACT FROM AUTHOR]

Background: Lack of insurance is associated with poorer outcomes in hospitalized patients. However, few studies have explored this association in hospitalizations for necrotizing soft tissue infections (NSTIs). This study examined the impact of insurance status on the outcome of NSTI admissions. Methods: All adult hospitalizations for necrotizing fasciitis, gas gangrene, and Fournier gangrene between 2016 and 2018 were examined using the Nationwide Inpatient Sample database. Insurance status was categorized as insured (including Medicare, Medicaid, and Private, including Health maintenance organization (HMO) or uninsured (Self-pay). Outcome measures included mortality rates, limb loss, length of hospital stay, prolonged hospital stay, and critical care admissions. Statistical analysis included weighted sample analysis, chi-square tests, multivariate regression analysis, and negative binomial regression modeling. Results: Approximately 29,705 adult hospitalizations for NSTIs were analyzed. Of these, 57.4% (17,065) were due to necrotizing fasciitis, 22% (6,545) to gas gangrene, and 20.5% (6,095) to Fournier gangrene. Approximately 9.7% (2,875) were uninsured, whereas 70% (26,780) had insurance coverage. Among the insured, Medicare covered 39.6% (10,605), Medicaid 29% (7,775), and private insurance 31.4% (8,400). After adjustments, Medicare insurance was associated with greater odds of mortality (adjusted odds ratio [aOR]: 1.81; 95% confidence interval [CI]: 1.33–2.47; p = 0.001). Medicaid insurance was associated with increased odds of amputation (aOR: 1.81; 95% CI: 1.33–2.47; p < 0.001), whereas private insurance was associated with lower odds of amputation (aOR: 0.70; 95% CI: 0.51–0.97; p = 0.030). Medicaid insurance was associated with greater odds of prolonged hospital stay (aOR: 1.34; 95% CI: 1.09–1.64; p < 0.001). No significant association was observed between the lack of insurance or self-pay and the odds of primary or secondary outcomes. Conclusion: Medicare insurance was correlated with greater odds of mortality, whereas Medicaid insurance was associated with increased odds of amputation and longer hospital stay. Uninsured status was not associated with significant differences in NSTI outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Clostridium perfringens is conditionally pathogenic, and its pathogenicity is caused by the toxins that it produces. Among these, the alpha toxin, produced by all subtypes of Clostridium perfringens, can cause enteritis or enterotoxemia in lambs, cattle, pigs, and horses, as well as traumatic clostridial myonecrosis in humans and animals, with high mortality. Therefore, the neutralization of the alpha toxin is crucial for the prevention and treatment of diseases caused by Clostridium perfringens. Here, the alpha toxin expressed in a prokaryotic expression vector was used to screen a nanobody against the alpha toxin from the natural nanobody library of an alpaca resource. The nanobody was characterized as having a half-life of 2.8 h, an affinity constant of 0.9 nmol/L, and good stability below 60 °C. The nanobody could effectively neutralize the phospholipase and hemolytic activity of the alpha toxin at a 15-fold ratio. In both Vero cells and model mice, the nanobody could neutralize the cytotoxicity of 2 × IC50 alpha toxin at certain concentrations, and it could rescue the cells and prevent the deaths of the mice. In conclusion, the specific nanobody against the alpha toxin could effectively neutralize the alpha toxin in Vero cells and mouse models, providing an anti-Clostridium perfringens toxin-related therapeutic product to inhibit the pathogenicity resulting from such toxins. All subtypes of Clostridium perfringens (C. perfringens) produce the alpha toxin (CPA), which can cause enteritis or enterotoxemia in lambs, cattle, pigs, and horses, as well as traumatic clostridial myonecrosis in humans and animals. CPA acts on cell membranes, ultimately leading to endocytosis and cell death. Therefore, the neutralization of CPA is crucial for the prevention and treatment of diseases caused by C. perfringens. In this study, utilizing CPA as an antigen, a nanobody (CPA-VHH) with a half-life of 2.9 h, an affinity constant (KD) of 0.9 nmol/L, and good stability below 60 °C was prepared from a natural nanobody library from alpacas. The biological activity analysis of CPA-VHH revealed its ability to effectively neutralize the phospholipase and hemolytic activity of CPA at a 15-fold ratio. In Vero cells, 9.8 μg/mL CPA-VHH neutralized the cytotoxicity of CPA at two times the half-maximal inhibitory concentration (IC50). In a mouse model, 35.7 ng/g body weight (BW) of CPA-VHH neutralized 90% of the lethality caused by a 2× median lethal dose (LD50) of CPA. It was found that CPA-VHH protected 80% of mice within 30 min at 2 × LD50 CPA, but this dropped below 50% after 2 h and to 0% after 4 h. Rescue trials indicated that using CPA-VHH within 30 min post-infection with 2 × LD50 CPA achieved an 80% rescue rate, which decreased to 10% after 2 h. Furthermore, CPA-VHH effectively mitigated the reduction in the expression levels of zonula occludens-1 (ZO-1), Occludin, and Claudin-1, while also attenuating the upregulation of the pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-7 (IL-7), interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) induced by CPA infection. Overall, this study has identified a specific nanobody, CPA-VHH, that effectively neutralizes CPA toxins in vitro and in animal models, providing a new tool for inhibiting the pathogenicity resulting from these toxins and laying an important foundation for the development of new anti-C. perfringens toxin-related therapeutic products. [ABSTRACT FROM AUTHOR]

Clostridial myonecrosis, commonly known as gas gangrene (GG), is a rapidly progressing and potentially fatal bacterial infection that primarily affects muscle and soft tissue. In the United States, the incidence of GG is roughly 1000 cases per year, while, in developing countries, the incidence is higher. This condition is most often caused by Clostridium perfringens, a Gram-positive, spore-forming anaerobic bacterium widely distributed in the environment, although other Clostridium species have also been reported to cause GG. The CP genome contains over 200 transport-related genes, including ABC transporters, which facilitate the uptake of sugars, amino acids, nucleotides, and ions from the host environment. There are two main subtypes of GG: traumatic GG, resulting from injuries that introduce Clostridium spores into deep tissue, where anaerobic conditions allow for bacterial growth and toxin production, and spontaneous GG, which is rarer and often occurs in immunocompromised patients. Clostridium species produce various toxins (e.g., alpha, theta, beta) that induce specific downstream signaling changes in cellular pathways, causing apoptosis or severe, fatal immunological conditions. For example, the Clostridium perfringens alpha toxin (CPA) targets the host cell's plasma membrane, hydrolyzing sphingomyelin and phosphatidylcholine, which triggers necrosis and apoptosis. The clinical manifestations of clostridial myonecrosis vary. Some patients experience the sudden onset of severe pain, swelling, and muscle tenderness, with the infection progressing rapidly to widespread tissue necrosis, systemic toxicity, and, if untreated, death. Other patients present with discharge, pain, and features of cellulitis. The diagnosis of GG primarily involves clinical evaluation, imaging studies such as X-rays, computer tomography (CT) scans, and culture. The treatment of GG involves surgical exploration, broad-spectrum antibiotics, antitoxin, and hyperbaric oxygen therapy, which is considered an adjunctive treatment to inhibit anaerobic bacterial growth and enhance the antibiotic efficacy. Early recognition and prompt, comprehensive treatment are critical to improving the outcomes for patients affected by this severe and life-threatening condition. [ABSTRACT FROM AUTHOR]

Absent in melanoma 2 (AIM2), a key component of the IFI20X/IFI16 (PYHIN) protein family, is characterized as a DNA sensor to detect cytosolic bacteria and DNA viruses. However, little is known about its immunological role during pathogenic Clostridium perfringens (C. perfringens) infection, an extracellular bacterial pathogen. In a pathogenic C. perfringens gas gangrene model, Aim2−/− mice are more susceptible to pathogenic C. perfringens soft tissue infection, revealing the importance of AIM2 in host protection. Notably, Aim2 deficiency leads to a defect in bacterial killing and clearance. Our in vivo and in vitro findings further establish that inflammasome signaling is impaired in the absence of Aim2 in response to pathogenic C. perfringens. Mechanistically, inflammasome signaling downstream of active AIM2 promotes pathogen control. Importantly, pathogenic C. perfringens-derived genomic DNA triggers inflammasome signaling activation in an AIM2-dependent manner. Thus, these observations uncover a central role for AIM2 in host defense and triggering innate immunity to combat pathogenic C. perfringens infections. [ABSTRACT FROM AUTHOR]

Clostridium perfringens alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of C. perfringens and is the major virulence determinant of C. perfringens type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for Staphylococcus aureus β-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis. [ABSTRACT FROM AUTHOR]

A patient presented with fever, severe pain and edematous tight due to hip trauma and was scheduled for urgent fasciotomy. Following physical examination, laboratory analyses were requested, and results revealed anemia and severe infection. As the patient's condition was serious, a new set of samples was sent to the laboratory four hours later. Following centrifugation, severely hemolyzed dark-colored serum and plasma samples were obtained and in vitro hemolysis was suspected. The collection of samples was repeated, but a new set of samples was also hemolyzed with a significant decrease in the hemoglobin value. At that point, in vivo hemolysis was suspected, and samples were processed according to standard laboratory procedures for hemolytic samples. Following confirmation of the gas gangrene diagnosis by clinicians, the cause of hemolysis was attributed to the cytotoxic activity of a-toxin produced by the anaerobic gram-positive bacterium Clostridium perfringens. An insight into the laboratory procedure that could help to narrow down the causes of hemolysis and single out C. perfringens as a cause of intravascular hemolysis was given. [ABSTRACT FROM AUTHOR]

The incidence, treatment, and outcomes of necrotizing soft tissue infections (NSTIs) and associated racial disparities have been described in adults, but research in the pediatric population is limited. The purpose of this study is to provide a nationally representative characterization of pediatric NSTI and determine the presence of any racial disparities. The National Inpatient Sample was analyzed from 2016 through 2020. Patients aged less than 20 y with a diagnosis of necrotizing fasciitis, Fournier's gangrene, or gas gangrene (based on International Classification of Diseases, Tenth Revision, Clinical Modification codes) were included for analysis. A total of 355 patients were identified. Black and Hispanic patients accounted for the most admissions in 2016 and 2018, respectively (P = 0.024). Compared to White patients, more Black patients were insured by Medicaid (P = 0.037) and were in the first zip code–based income quartile (P = 0.005). The leading infection overall was necrotizing fasciitis and most patients (81.7%) underwent a surgical procedure by the first calendar day after admission. Although the proportion of Black patients undergoing subcutaneous tissue and fascia excisions was more than that of White patients (P = 0.005), there were no significant differences by race in the time to first procedure, the total number of procedures, or number of postoperative complications. Our amputation and mortality rates were low and unreportable, but there were no differences by race. NSTI is rare in the pediatric population and mortality is low. Black patients are disproportionately diagnosed, but these disparities do not extend to disease treatment or outcomes. [ABSTRACT FROM AUTHOR]

Clostridial infections in goats have been associated frequently with enteric diseases or gas gangrene but very rarely with the reproductive system. We describe here 12 cases of fatal postpartum gangrenous metritis in does associated with infection by several clostridial species. Clinically, these cases were characterized by rapid onset of hyperthermia followed by death after kidding. On postmortem examination, the uteri appeared to be necrotic and were hemorrhagic and edematous. Microscopically, the uteri had diffuse coagulative necrosis, edema, hemorrhage, and fibrinous thrombi with intralesional gram-positive rods. Clostridium perfringens was isolated from 7 of 9 uterine samples cultured, and C. perfringens, C. septicum, C. novyi, or C. chauvoei were demonstrated by immunohistochemistry (IHC) in the 5 cases examined. IHC for Paeniclostridium sordellii was negative in all 5 cases. PCR performed on 3 of the C. perfringens isolates was positive for alpha toxin and perfringolysin, identifying these isolates as type A. Clostridial infection should be considered in cases of postpartum gangrenous metritis of does.

Background: Necrotizing soft tissue infections (NSTIs) are rare but deadly infections that require early and often extensive surgical debridement. After debridement, patients frequently have substantial morbidity because of large, open wounds. Hypothesis: Negative pressure wound therapy with instillation (NPWTi) results in higher wound closure rates compared with traditional negative pressure wound therapy (NPWT) or wet to dry dressings (moist wound care dressing). Patients and Methods: A prospectively maintained Acute and Critical Care Surgery database spanning 2008–2018 was queried for patients with a diagnosis of necrotizing fasciitis, Fournier gangrene, or gas gangrene. Data were collected on patient comorbidities, operative management, and clinical outcomes. Patients were stratified by use of moist wound care dressing, traditional NPWT, or NPWTi. Data were analyzed using analysis of variance (ANOVA), χ2, and logistic regression. Results: During the 10-year study period, patients were treated for NSTI; 173 were managed with moist wound care dressing, 150 with NPWT, and 48 with NPWTi. Patients were similar in terms of demographics, body mass index (BMI), diabetes mellitus, and smoking rates. Overall, complication rates were not substantially different, but mortality was higher in the moist wound care dressing group (16.2% vs. 10.7% NPWT vs. 2.1% NPWTi; p = 0.02). In the moist wound care dressing group, 81.5% of patients had an open wound at discharge compared with 52.7% of the NPWT group and only 14.6% of the NPWTi group (p < 0.001). On multivariable regression, NPWTi was associated with closure rates five times higher than the NPWT group (odds ratio [OR], 5.28; 95% confidence interval [CI], 2.40–11.61; p < 0.001) after controlling for smoking status, intravenous drug use, number of operations, and involvement of the most common region of the body. Conclusions: Negative pressure wound therapy with instillation is associated with higher rates of wound closure without increasing complication rates in patients with NSTI compared with traditional NPWT or moist wound care dressing. Although prospective studies are needed, this indicates the potential to improve patient quality of life through reduced pain and outpatient home health needs. [ABSTRACT FROM AUTHOR]

Objective: The main uses of hyperbaric oxygen therapy (HBOT) in orthopaedics are acute traumatic ischemia such as crush injuries and compartment syndrome, reimplantations, chronic osteomyelitis, grafts and flaps with suspected involvement, gas gangrene, necrotizing soft tissue infections, avascular necrosis and delayed post-op wound healing. The aim of this study was to determine the most common orthopaedic indications for HBOT in pediatrics. We also aimed to share information about HBOT with pediatric orthopaedic surgeons. Method: By reviewing our files and system records, we documented all pediatric patients who underwent HBOT between 01.01.2006 and 01.01.2016 with the indications of crush injury, compartment syndrome, chronic osteomyelitis and delayed wound healing. We recorded the demographic characteristics, indications, outcomes, problems encountered, complications and side effects of patients aged 0-18 years who received at least 15 sessions of HBOT. Results: A total of 1029 HBOT sessions were performed in 31 patients. Treatment was completed as planned in 24 patients (77.4%). Cure was achieved in 19 patients (61.3%). Two patients (6.4%) had improvement with minor morbidity, and three (9.7%) had no improvement as a result of the treatment. Anxiety symptoms were observed in only six patients during the first session (0.6% patient sessions). The sessions did not result in any complications that required treatment to be discontinued. Conclusion: HBOT in patients with orthopaedic indications was completed without complications. We believe that HBOT can be safely used in pediatric orthopaedics. However, larger patient series are needed. [ABSTRACT FROM AUTHOR]

Gas gangrene is a rare, severe gas-producing infection that can be related to colorectal cancer. Gas gangrene can be confirmed by radiologic findings and crepitation on touch. Spontaneous gas gangrene can be associated with colorectal cancer. An 80-year-old female complaint about a sudden abdominal pain, accompanied with progressive swelling pain in thigh and fever. Diagnosis based on assessment findings were gas gangrene and descending colonic cancer perforation. Emergency surgery was performed for debridement and drainage, followed by vacuum sealing drainage (VSD) with polyurethane (PU). Two more surgical interventions were given before the colonic tumor surgery. The patient recovered well in the long-term follow-up. This report demonstrates the diagnosis, treatment, and management of a successful case of gas gangrene caused by perforation of descending colonic cancer. Accurate preoperative diagnosis and reasonable use of VSD (PU) material played an important role in the treatment of this case. [ABSTRACT FROM AUTHOR]

Skin and soft tissue infections (SSTIs) result from microbial invasion and may be mono or polymicrobial in etiology. The present retrospective record based study described five uncommon SSTIs from a medical college hospital of West Bengal. Clinical samples were collected and processed following standard microbiological procedures and guidelines. Identification and antimicrobial susceptibility testing of etiological agents, wherever applicable, were done by conventional and automated (Vitek-2 Compact) system. We found a case of spontaneous gas gangrene caused by Clostridium septicum, Group-A â-hemolytic Streptococcus mediated necrotizing fasciitis; lesions of Burkholderia pseudomallei and Burkholderia cepacia complex and that of disseminated rhinosporidiosis caused by Rhinosporidium seeberi. We infer that strong clinical suspicion may surface uncommon etiology from unusual presentations of SSTIs making their diagnosis, treatment and relief rapid and uneventful. [ABSTRACT FROM AUTHOR]

Introduction: There are inconsistencies in outcome reporting for patients with necrotising soft tissue infections (NSTI). The aim of this study was to evaluate reported outcome measures in NSTI literature that could inform a core outcome set (COS) such as could be used in a study of hyperbaric oxygen in this indication. Methods: A systematic review of all NSTI literature identified from Cochrane, Ovid MEDLINE and Scopus databases as well as grey literature sources OpenGrey and the New York Academy of Medicine databases which met inclusion criteria and were published between 2010 and 2020 was performed. Studies were included if they reported on > 5 cases and presented clinical endpoints, patient related outcomes, or resource utilisation in NSTI patients. Studies did not have to include intervention. Two independent researchers then extracted reported outcome measures. Similar outcomes were grouped and classified into domains to produce a structured inventory. An attempt was made to identify trends in outcome measures over time and by study design. Results: Three hundred and seventy-five studies were identified and included a total of 311 outcome measures. Forty eight percent (150/311) of outcome measures were reported by two or more studies. The four most frequently reported outcome measures were mortality without time specified, length of hospital stay, amputation performed, and number of debridements, reported in 298 (79.5%), 260 (69.3%), 156 (41.6%) and 151 (40.3%) studies respectively. Mortality outcomes were reported in 23 different ways. Randomised controlled trials (RCTs) were more likely to report 28-day mortality or 90-day mortality. The second most frequent amputation related outcome was level of amputation, reported in 7.5% (28/375) of studies. The most commonly reported patient-centred outcome was the SF-36 which was reported in 1.6% (6/375) of all studies and in 2/10 RCTs. Conclusions: There was wide variance in outcome measures in NSTI studies, further highlighting the need for a COS. [ABSTRACT FROM AUTHOR]

Dr Agnes Savill was the UK's first female consultant dermatologist with a career journey which was, by any standards, extraordinary. She was awarded her MA in 1893 making her the first female graduate from St Andrews University. She then trained as a doctor in Glasgow in the earliest cohort of women granted the opportunity to study medicine. Following qualification, and during her early professional years, she maintained an involvement in the women's suffrage movement by publicly indicting the government for its brutal treatment of women suffrage prisoners in the 'Votes for Women' campaign. During World War 1 Dr Agnes Savill was one of a handful of women doctors who served at the Scottish Women's Hospital, a combat hospital in France. Dr Savill worked as the radiologist for the unit and developed expertise in the radiographic appearances of gas gangrene. After the war she returned to her dermatology practice, becoming the UK's leading expert in disorders of the hair and scalp and publishing widely on the subject. However, Agnes Savill had interests which extended into the humanities, particularly music. She was advocate for the use of music as treatment for psychological and physical disorders and wrote a book on this subject which helped promote music therapy as a para-clinical discipline. In her latter years she became fascinated by the history of classical antiquity and, at the age of 79, published a biography of Alexander the Great, an account praised for being both lucid and authoritative. Agnes Savill was a remarkable pioneering doctor: she was a ground-breaking dermatologist, she fought for women's rights and served in France as a combat doctor. Her work in music therapy and her writings on ancient history brought acclaim beyond the realm of medicine. Dr Agnes Savill is Dermatology's Renaissance Woman. [ABSTRACT FROM AUTHOR]

This article discusses a case of a young heifer that died suddenly on a farm, showing symptoms of increased respiratory rate and elevated temperature. The necropsy revealed necrohemorrhagic myocarditis and myositis, with the presence of Clostridium chauvoei, the causative agent of blackleg disease. Blackleg is a common disease in young, well-fed cattle and can cause limb weakness, fever, and muscle swelling. The article emphasizes the importance of recognizing and diagnosing blackleg in order to prevent further outbreaks. The disease is characterized by the production of toxins that lead to localized tissue damage and systemic toxemia. Vaccination is available and has been shown to be effective in protecting animals from severe clinical disease. The presence of C. chauvoei can be confirmed through various testing methods, and the spores can be transmitted through environmental exposure or contaminated feed. [Extracted from the article]

C. perfringens, a ubiquitous bacterium, is implicated in a series of recent outbreaks across Europe, reflecting its significance in public health. The organism manifests different clinical presentations in both human and animal hosts. In the realm of veterinary science, its pathogenesis in species such as poultry, cattle, swine, and equines is of particular concern due to the economic implications stemming from morbidity and mortality rates. The enterotoxins produced by this bacterium is the primary cause of symptoms like watery diarrhea, abdominal pains, and cramps in humans, and leads to conditions such as clostridial myonecrosis and necrotic enteritis in animals. An important aspect of its virulence strategy is its ability to form biofilms. These sophisticated microbial assemblages confer an augmented resistance against environmental challenges and antimicrobial interventions. This review consolidates information about C. perfringens outbreaks in Europe, mode of infection, pathogenesis in various animals, associated clinical symptoms, and the nuances of its biofilm formation. The present literature synthesis could provide valuable insights for forthcoming preventive and therapeutic initiatives. [ABSTRACT FROM AUTHOR]

Bacteria of the genus Clostridium are anaerobic Gram-positive spore-forming bacilli that include more than 200 species. Some of them are known to cause invasive infections and diseases caused by the production of toxins. Some of the diseases that are mediated by toxins are colitis in patients with specific risk factors, such as previous administration of antimicrobials or foodborne botulism. Invasive diseases include bacteremia, infective endocarditis (IE), clostridial myonecrosis (gas gangrene), and other diseases that involve the destruction of soft tissue due to the local production of toxins. The present study aimed to review all cases of IE by Clostridioides and Clostridium species and describe the epidemiology, clinical characteristics, treatment, and outcomes of these infections. A narrative review was performed based on a search in PubMed and Scopus for studies published until 11 September 2023, providing such data of IE caused by Clostridioides and Clostridium species in humans. A total of 20 studies containing data for 21 patients were included. A prosthetic valve was present in 5 patients (23.8%). The aortic valve was the most commonly involved, followed by the mitral valve. Fever, sepsis, and embolic phenomena were the most common clinical presentations. Beta-lactams and metronidazole were the most commonly used antimicrobials. Surgery was performed in nine patients (45%). Mortality reached 33.3%. IE in multiple valves was associated with increased mortality. Despite the heterogeneous genetic and molecular characteristics that necessitate the taxonomic change of some of this genus's previous members, the clinical syndrome of IE caused by these bacteria seems to have similar characteristics. [ABSTRACT FROM AUTHOR]

Edwardsiella tarda (E. tarda), a gram-negative bacillus, a member of order Enterobacterales , is typically a fish pathogen frequently isolated from fresh and brackish water environments. It is very rarely implicated in human infections such as gastroenteritis (most common), cellulitis, gas gangrene, hepatobiliary infections, peritonitis, empyema, and meningitis. Bacteremia/sepsis caused by E. tarda can be fatal in humans, although very rare (<5%). To date, very few cases of E. tarda sepsis have been reported worldwide including India. We report a rare case of cellulitis caused by E. tarda following fishbone injury in a patient with underlying hematological malignancy leading to sepsis. [ABSTRACT FROM AUTHOR]

Clostridium perfringens can cause a plethora of diseases in humans and animals, making it a growing public health concern. Insight into C. perfringens genomic studies has enhanced our understanding of the diversity and evolution of this bacterium. However, most of these studies were centered on clinical strains from human and animal hosts, with limited data from environmental sources and developing countries. Here, we present genomic and phenotypic insights into C. perfringens strains from hospital wastewater samples from Ghana. Antibiotic susceptibility testing, toxinotyping, and whole-genome sequencing were performed on the seven C. perfringens isolates. The strains were susceptible to all antibiotics screened except for three strains that were resistant to clindamycin. The majority of these strains were type F strains, characterized by a chromosomally encoded cpe gene, whereas the remaining strains were classified as type A. The cpe gene is flanked upstream by IS1469 and downstream by IS1470. The genotype for the type F strains was ST721, whereas the type A strains were assigned to ST722, ST143, and ST211. Our type F strains clustered with other strains all within phylogroup I, which are mostly associated with foodborne illnesses, whereas the type A strains were grouped within phylogroup III. This study provides the first genomic characterization of C. perfringens from West Africa and contributes to further understanding of genomic diversity in C. perfringens. Moreover, the possible disseminated situation of C. perfringens in the environment highlights the need to monitor this bacterium in clinical specimens in Ghana. IMPORTANCE Clostridium perfringens causes gas gangrene and food poisoning in humans, and monitoring this bacterium is important for public health. Although whole-genome sequencing is useful to comprehensively understand the virulence, resistome, and global genetic relatedness of bacteria, limited genomic data from environmental sources and developing countries hamper our understanding of the richness of the intrinsic genomic diversity of this pathogen. Here, we successfully accumulated the genetic data on C. perfringens strains isolated from hospital effluent and provided the first evidence that predicted pathogenic C. perfringens may be disseminated in the clinical environment in Ghana. Our findings suggest the importance of risk assessment in the environment as well as the clinical setting to mitigate the potential outbreak of C. perfringens food poisoning in Ghana. [ABSTRACT FROM AUTHOR]

Background: The breast milk bank is a professional organization that collects donor human milk (DHM) for special medical needs by recruiting qualified breast milk donors. Such organizations are also responsible for the disinfection, processing, testing, storage, distribution, and use of breast milk. As DHM is a biological product, it may get contaminated. Microbiological testing is the final step to determine microbial contamination of DHM. However, a universal method for the microbiological analysis of DHM in breast milk banks globally is lacking.DHM without strict screening may become a potential carrier of pathogens and seriously threaten the health of infants. Clostridium perfringens, a gram-positive anaerobic bacterium, is capable of causing wound infections, including gas gangrene, enteritis/enterocolitis, and enterotoxemia. Here, the first case of C. perfringens detected in DHM has been reported to facilitate the identification of such contamination in breast milk banks. Case presentation: A breastfeeding mother donated 3000 mL of milk to the breast milk bank of the First Affiliated Hospital of the Army Medical University(over 2900 beds and patient receiving capacity of over 132,000), Chongqing, China. The milk sample was subjected to microbiological screening using liquid enrichment, followed by anaerobic and aerobic culturing. The results revealed the growth of C. perfringens in the anaerobic culture medium, but no bacteria or yeast-like fungi were observed in the aerobic culture medium. The donor did not exhibit any clinical symptoms, and her routine blood results and body temperature were normal. However, the infant fed with her milk had recurrent bloody stools. Breast milk bank infection control emergency handling as well as environmental sampling and investigation revealed that the cause was contamination of the donor's home-use breast pump with C. perfringens. The infant no longer experienced bloody stool once the donor changed the breast pump. Conclusions: C. perfringens can enter breast milk from contaminated pumping environments or devices, thus causing illness in infants. The microbiological testing of DHM in breast milk banks can be accomplished using liquid enrichment, along with anaerobic and aerobic culture, which is of immense significance in improving the standards for microbiological screening, DHM safety, and infant health. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives TNF-like weak inducer of apoptosis (TWEAK) and its sole receptor fibroblast growth factor-inducible 14 (Fn14) are involved in various inflammatory conditions. This study was performed to investigate the potential role of TWEAK/Fn14 in immune-mediated necrotizing myopathy (IMNM). Methods Muscle biopsies from patients with IMNM (n  = 37) and controls (n  = 11) were collected. Human muscle cells were treated with TWEAK in vitro. Muscle biopsies and cultured muscle cells were analysed by immunostaining and quantitative PCR. Serum levels of TWEAK and Fn14 were detected by ELISA. Results TWEAK and Fn14 were overexpressed in IMNM muscle biopsies. The percentage of Fn14-positive myofibers correlated with disease severity, myonecrosis, regeneration and inflammation infiltrates. Fn14-positive myofibers tended to be surrounded or invaded by CD68 + macrophages. TWEAK treatment had a harmful effect on cultured muscle cells by inducing the production of multiple chemokines and pro-inflammatory cytokines. Serum Fn14 levels were increased in patients with IMNM and correlated with muscle weakness. Conclusions TWEAK/Fn14 signalling was activated in IMNM, most likely aggravating muscle damage via amplifying inflammatory response and macrophages chemotaxis. Fn14 seems to be a biomarker for assessing disease severity in IMNM. In addition, Fn14 may also contribute to muscle injury repair. [ABSTRACT FROM AUTHOR]

Skin and soft tissue infections (SSTIs) result from microbial invasion and may be mono or polymicrobial in etiology. The present retrospective record-based study described five uncommon SSTIs from a medical college hospital of West Bengal. Clinical samples were collected and processed following standard microbiological procedures and guidelines. Identification and antimicrobial susceptibility testing of etiological agents, wherever applicable, were done by conventional and automated (Vitek-2 Compact) system. We found a case of spontaneous gas gangrene caused by Clostridium septicum, Group-A â-hemolytic Streptococcus mediated necrotizing fasciitis; lesions of Burkholderia pseudomallei and Burkholderia cepacia complex and that of disseminated rhinosporidiosis caused by Rhinosporidium seeberi. We infer that strong clinical suspicion may surface uncommon etiology from unusual presentations of SSTIs making their diagnosis, treatment and relief rapid and uneventful.

The clostridial diseases of horses can be divided into three major groups: enteric/enterotoxic, histotoxic, and neurotoxic. The main enteric/enterotoxic diseases include those produced by Clostridium perfringens type C and Clostridioides difficile, both of which are characterized by enterocolitis. The main histotoxic diseases are gas gangrene, Tyzzer disease, and infectious necrotic hepatitis. Gas gangrene is produced by one or more of the following microorganisms: C. perfringens type A, Clostridium septicum, Paeniclostridium sordellii, and Clostridium novyi type A, and it is characterized by necrotizing cellulitis and/or myositis. Tyzzer disease is produced by Clostridium piliforme and is mainly characterized by multifocal necrotizing hepatitis. Infectious necrotic hepatitis is produced by Clostridium novyi type B and is characterized by focal necrotizing hepatitis. The main neurotoxic clostridial diseases are tetanus and botulism, which are produced by Clostridium tetani and Clostridium botulinum, respectively. Tetanus is characterized by spastic paralysis and botulism by flaccid paralysis. Neither disease present with specific gross or microscopic lesions. The pathogenesis of clostridial diseases involves the production of toxins. Confirming a diagnosis of some of the clostridial diseases of horses is sometimes difficult, mainly because some agents can be present in tissues of normal animals. This paper reviews the main clostridial diseases of horses.

Clostridium perfringens is an extremely versatile pathogen of humans and livestock, causing wound infections like gas gangrene (clostridial myonecrosis), enteritis/enterocolitis (including one of the most common human food-borne illnesses), and enterotoxemia (where toxins produced in the intestine are absorbed and damage distant organs such as the brain). The virulence of this Gram-positive, spore-forming, anaerobe is largely attributable to its copious toxin production; the diverse actions and roles in infection of these toxins are now becoming established. Most C. perfringens toxin genes are encoded on conjugative plasmids, including the pCW3-like and the recently discovered pCP13-like plasmid families. Production of C. perfringens toxins is highly regulated via processes involving two-component regulatory systems, quorum sensing and/or sporulation-related alternative sigma factors. Non-toxin factors, such as degradative enzymes like sialidases, are also now being implicated in the pathogenicity of this bacterium. These factors can promote toxin action in vitro and, perhaps in vivo, and also enhance C. perfringens intestinal colonization, e.g. NanI sialidase increases C. perfringens adherence to intestinal tissue and generates nutrients for its growth, at least in vitro. The possible virulence contributions of many other factors, such as adhesins, the capsule and biofilms, largely await future study.

Clostridium perfringens is an extremely versatile pathogen of humans and livestock, causing wound infections like gas gangrene (clostridial myonecrosis), enteritis/enterocolitis (including one of the most common human food-borne illnesses), and enterotoxemia (where toxins produced in the intestine are absorbed and damage distant organs such as the brain). The virulence of this Gram-positive, spore-forming, anaerobe is largely attributable to its copious toxin production; the diverse actions and roles in infection of these toxins are now becoming established. Most C. perfringens toxin genes are encoded on conjugative plasmids, including the pCW3-like and the recently discovered pCP13-like plasmid families. Production of C. perfringens toxins is highly regulated via processes involving two-component regulatory systems, quorum sensing and/or sporulation-related alternative sigma factors. Non-toxin factors, such as degradative enzymes like sialidases, are also now being implicated in the pathogenicity of this bacterium. These factors can promote toxin action in vitro and, perhaps in vivo, and also enhance C. perfringens intestinal colonization, e.g. NanI sialidase increases C. perfringens adherence to intestinal tissue and generates nutrients for its growth, at least in vitro. The possible virulence contributions of many other factors, such as adhesins, the capsule and biofilms, largely await future study.

Acute pancreatitis is a common condition, only occasionally leading to necrosis of the pancreas. In instances where abscess formation takes place, the predominant microbial profile involves both aerobic and anaerobic enteric species. We present the case of a patient with clostridial emphysematous pancreatitis who developed pneumoperitoneum without associated visceral perforation. [ABSTRACT FROM AUTHOR]

Catheter-related suppurative thrombophlebitis (CRST) is a complication of catheter-related bloodstream infection (CRBSI). The microbiology of CRST is similar with the microbiology of CRBSI, but Clostridium perfringens that causes gas gangrene is a rare pathogen of CRBSI and CRST. We present a case of catheter-related gas-forming suppurative thrombophlebitis due to Clostridium perfringens infection. Gas-forming thrombus around the catheter can be useful findings for the early diagnosis of catheter-related clostridial thrombophlebitis. [ABSTRACT FROM AUTHOR]

Absent in melanoma 2 (AIM2), a key component of the IFI20X/IFI16 (PYHIN) protein family, is characterized as a DNA sensor to detect cytosolic bacteria and DNA viruses. However, little is known about its immunological role during pathogenic Clostridium perfringens (C. perfringens) infection, an extracellular bacterial pathogen. In a pathogenic C. perfringens gas gangrene model, Aim2−/− mice are more susceptible to pathogenic C. perfringens soft tissue infection, revealing the importance of AIM2 in host protection. Notably, Aim2 deficiency leads to a defect in bacterial killing and clearance. Our in vivo and in vitro findings further establish that inflammasome signaling is impaired in the absence of Aim2 in response to pathogenic C. perfringens. Mechanistically, inflammasome signaling downstream of active AIM2 promotes pathogen control. Importantly, pathogenic C. perfringens-derived genomic DNA triggers inflammasome signaling activation in an AIM2-dependent manner. Thus, these observations uncover a central role for AIM2 in host defense and triggering innate immunity to combat pathogenic C. perfringens infections.

Abstract Background Necrotizing fasciitis in neonates is a rare and life-threatening infection involving necrosis of the skin, subcutaneous tissues, deep fascia, and sometimes underlying muscles, with a fulminant course and high mortality rate. Necrotizing fasciitis with gas gangrene related to infection of a peripherally inserted central catheter is very rare. Case presentation The patient was a full-term female neonate born by vaginal delivery. Following diagnosis of patent ductus arteriosus, indomethacin was administered from a peripherally inserted central catheter for 3 days. Four days after the termination of medical treatment for the patent ductus arteriosus, the patient developed fever and a severely elevated inflammatory response was identified from blood testing. Around the right anterior chest wall, corresponding to the site of the catheter tip, redness was increased and gas crepitus was felt under the skin. Computed tomography revealed emphysema in the anterior chest, in subcutaneous areas and between muscles. Emergency surgical debridement was performed under a diagnosis of necrotizing fasciitis with gas gangrene. With antibiotic treatment, we started to fill the wound with a dialkyl carbamoyl chloride-coated dressing and povidone-iodine sugar ointment after washing with saline once a day. The patient survived and after 3 weeks of treatment with the dressing, the wound had successfully resolved without motor impairments. Conclusions In addition to medical treatment and prompt surgical debridement, we used dialkyl carbamoyl chloride-coated dressing and povidone-iodine sugar ointment for antiseptic dressings and successfully treated neonatal necrotizing fasciitis with gas gangrene caused by peripherally inserted central catheter infection with Citrobacter koseri.

Clostridium perfringens bacteremia is a rare but rapidly fatal condition, especially in patients exhibiting massive intravascular hemolysis (MIH), gas gangrene, and septic shock. Herein, we present an autopsy case of C. perfringens septicemia exhibiting MIH, gas gangrene, and cytokine storm. The patient was an 84-year-old female with a history of biliary reconstruction surgery for congenital biliary dilatation. She developed MIH, elevated inflammatory mediator levels, thrombocytopenia, and coagulopathy. She went into shock within 1 h of the presentation and died within a few hours. Rapid progression was associated with the transformation of liver abscesses into gas-filled abscesses on computed tomography scan, suggesting the rapid outgrowth of gas-producing bacteria. The patient was finally diagnosed with MIH and gas gangrene due to C. perfringens infection based on the presence of this bacterium in the blood and bile. On autopsy, gas gangrene was observed in almost all organs, originating from the bile duct. Polymerase chain reactions targeting C. perfringens toxins identified the isolated bacterium as C. perfringens type A expressing α-toxin (CPA), perfringolysin O (PFO), and collagenase (ColA). Elevated interleukin 6 and tumor necrosis factor-α expression levels were observed in the serum, and such proinflammatory responses were partially mediated by Toll-like receptor 2. This study elucidated the association between the toxin profiles of clinically isolated C. perfringens and the host cytokine responses in the patient.

The alarming symptoms attributed to several potent clostridial toxins enabled the early identification of the causative agent of tetanus, botulism, and gas gangrene diseases, which belongs to the most famous species of pathogenic clostridia. Although Clostridioides difficile was identified early in the 20th century as producing important toxins, it was identified only 40 years later as the causative agent of important nosocomial diseases upon the advent of antibiotic therapies in hospital settings. Today, C. difficile is a leading public health issue, as it is the major cause of antibiotic-associated diarrhea in adults. In particular, severe symptoms within the spectrum of C. difficile infections are directly related to the levels of toxins produced in the host. This highlights the importance of understanding the regulation of toxin synthesis in the pathogenicity process of C. difficile, whose regulatory factors in response to the gut environment were first identified at the Institut Pasteur. Subsequently, the work of other groups in the field contributed to further deciphering the complex mechanisms controlling toxin production triggered by the intestinal dysbiosis states during infection. This review summarizes the Pasteurian contribution to clostridial toxin regulation studies. [ABSTRACT FROM AUTHOR]

Clostridium perfringens (C. perfringens) is widely distributed in soil and in the human and animal intestines and is the causative agent of gas gangrene and enterotoxaemia in humans and animals. When C. perfringens infect domestic animals, it causes diarrhea, multiple-organ bleeding, and nervous system disorders by releasing toxins. In this study, to identify the etiology and pathology of the acute cause of death in a Suffolk ram, 12 different tissues including heart, liver, spleen, lung, kidney, testis, mesenteric lymph nodes, cecum, colon, middle colon, ileum, and rectum from the dead sheep were collected and pathogen isolation was performed by using identification medium of C. perfringens and 5% defibrated sheep blood agar medium. 16S rRNA gene of the isolated strain was amplified and sequenced. Phylogenetic trees of isolates were constructed based on 16S rRNA sequences and genetic evolution was analyzed. The specific primers for toxin typing of cpa, cpb, etx, itx, and cpe were used to identify the isolated strains. The pathological changes of tissues and organs were observed by histopathology. The results showed that 12 C. perfringens type D strains were isolated from different tissues. Histopathological observation showed endocardial hemorrhage and muscle fiber degeneration and necrosis, liver tissue capsule hemorrhage and liver sinusoids dilatation and congestion, white pulp atrophy and lymphocytopenia in spleen, renal glomerular necrosis with interstitial inflammatory cell infiltration and fibrous tissue hyperplasia in kidney, exfoliation of intestinal villous epithelial cells from the ileum tissue with inflammatory cell infiltration and vasodilation and congestion, mucosal layer extensive necrosis and hemorrhage of the colon tissue with necrosis and exfoliation of epithelial cell and inflammatory cell infiltration and vascular dilation and congestion, inflammatory cell infiltration and vasodilatation congestion in cecal tissue, spermatogenic tubule atrophy in testis tissue and necrosis and reduction of spermatogenic cells serous with exudation of serous substances and other pathological changes. The results showed that the pathogenic bacteria that caused the death of the flock was C. perfringens type D, which was found in all visceral tissues. This study also proved that C. perfringens could invade the reproductive organs of rams and cause pathological damage. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Gas gangrene is a rapidly progressive and potentially fatal infection that is common in the extremities. Gas gangrene of the head and neck is a very rare condition, and non-clostridial gas-forming neck abscess caused by Klebsiella pneumoniae is unusual. This report is of a diabetic man with poor dental hygiene, a right dental abscess, and parapharyngeal abscess with gas gangrene due to Klebsiella pneumoniae infection, presenting with septic shock and multiorgan failure, who recovered after surgical neck debridement. Case Report: A 52-year-old man with diabetes mellitus lost consciousness and collapsed on a curbside. He presented with painful swelling of the right-side neck, associated with spiking fever, confusion, dyspnea, and stridor. He had right submandibular and supraclavicular swelling with crepitus, multiple dental caries, and multiorgan dysfunction, and was intubated. A computed tomography scan showed a gas-forming abscess in the right parapharyngeal, retropharyngeal, and paralaryngeal spaces and dense infiltration with pleural effusion in the upper lobes. Neck exploration was performed for drainage. Necrotic tissue and foul-smelling pus were debrided and drained. Gram stain showed gram-negative bacilli. Necrotic tissue, pus, and blood culture showed Klebsiella pneumoniae. He remained on intravenous meropenem for 14 days and was frequently debrided with irrigation until the infection subsided. Finally, normal physiologic functions of the failing organ system were restored. Conclusions: We present a rare case of Klebsiella pneumoniae infection causing gas gangrene in the deep neck spaces, leading to septic shock and multiorgan failure, who recovered after surgical neck debridement. This is a potentially fatal condition that requires emergency drainage because of its high mortality rate. [ABSTRACT FROM AUTHOR]

Background: Necrotizing fasciitis in neonates is a rare and life-threatening infection involving necrosis of the skin, subcutaneous tissues, deep fascia, and sometimes underlying muscles, with a fulminant course and high mortality rate. Necrotizing fasciitis with gas gangrene related to infection of a peripherally inserted central catheter is very rare. Case presentation: The patient was a full-term female neonate born by vaginal delivery. Following diagnosis of patent ductus arteriosus, indomethacin was administered from a peripherally inserted central catheter for 3 days. Four days after the termination of medical treatment for the patent ductus arteriosus, the patient developed fever and a severely elevated inflammatory response was identified from blood testing. Around the right anterior chest wall, corresponding to the site of the catheter tip, redness was increased and gas crepitus was felt under the skin. Computed tomography revealed emphysema in the anterior chest, in subcutaneous areas and between muscles. Emergency surgical debridement was performed under a diagnosis of necrotizing fasciitis with gas gangrene. With antibiotic treatment, we started to fill the wound with a dialkyl carbamoyl chloride-coated dressing and povidone-iodine sugar ointment after washing with saline once a day. The patient survived and after 3 weeks of treatment with the dressing, the wound had successfully resolved without motor impairments. Conclusions: In addition to medical treatment and prompt surgical debridement, we used dialkyl carbamoyl chloride-coated dressing and povidone-iodine sugar ointment for antiseptic dressings and successfully treated neonatal necrotizing fasciitis with gas gangrene caused by peripherally inserted central catheter infection with Citrobacter koseri. [ABSTRACT FROM AUTHOR]

The C. perfringens species is associated with various environments, such as soils, sewage, and food. However, it is also a component of the gastrointestinal (GI) microflora (i.e., microbiota) of sick and healthy humans and animals. C. perfringens is linked with different systemic and enteric diseases in livestock and humans, such as gas gangrene, food poisoning, non-foodborne diarrhoea, and enterocolitis. The strains of this opportunistic pathogen are known to secrete over 20 identified toxins that are considered its principal virulence factors. C. perfringens belongs to the anaerobic bacteria community but can also survive in the presence of oxygen. The short time between generations, the multi-production capability of toxins and heat-resistant spores, the location of many virulence genes on mobile genetic elements, and the inhabitance of this opportunistic pathogen in different ecological niches make C. perfringens a very important microorganism for public health protection. The epidemiological evidence for the association of these strains with C. perfringens–meditated food poisoning and some cases of non-foodborne diseases is very clear and well-documented. However, the genetic diversity and physiology of C. perfringens should still be studied in order to confirm the importance of suspected novel virulence traits. A very significant problem is the growing antibiotic resistance of C. perfringens strains. The aim of this review is to show the current basic information about the toxins, epidemiology, and genetic and molecular diversity of this opportunistic pathogen. [ABSTRACT FROM AUTHOR]

Clostridium perfringens type A is involved in gas gangrene in humans and animals. Following a traumatic injury, rapid bacterial proliferation and exotoxin production result in severe myonecrosis. C. perfringens alpha toxin (CPA) and perfringolysin (PFO) are the main virulence factors responsible for the disease. Recent in vitro studies have identified an Agr-like quorum-sensing (QS) system in C. perfringens that regulates the production of both toxins. The system is composed of an AgrB membrane transporter and an AgrD peptide that interacts with a two-component regulatory system in response to fluctuations in the cell population density. In addition, a synthetic peptide named 6-R has been shown to interfere with this signaling mechanism, affecting the function of the Agr-like QS system in vitro In the present study, C. perfringens type A strain ATCC 3624 and an isogenic agrB-null mutant were tested in a mouse model of gas gangrene. When mice were intramuscularly challenged with 106 CFU of wild-type ATCC 3624, severe myonecrosis and leukocyte aggregation occurred by 4 h. Similar numbers of an agrB-null mutant strain produced significantly less severe changes in the skeletal muscle of challenged mice. Complementation of the mutant to regain agrB expression restored virulence to wild-type levels. The burdens of all three C. perfringens strains in infected muscle were similar. In addition, animals injected intramuscularly with wild-type ATCC 3624 coincubated with the 6-R peptide developed less severe microscopic changes. This study provides the first in vivo evidence that the Agr-like QS system is important for C. perfringens type A-mediated gas gangrene.IMPORTANCE Clostridium perfringens type A strains produce toxins that are responsible for clostridial myonecrosis, also known as gas gangrene. Toxin production is regulated by an Agr-like quorum-sensing (QS) system that responds to changes in cell population density. In this study, we investigated the importance of this QS system in a mouse model of gas gangrene. Mice challenged with a C. perfringens strain with a nonfunctional regulatory system developed less severe changes in the injected skeletal muscle compared to animals receiving the wild-type strain. In addition, a synthetic peptide was able to decrease the effects of the QS in this disease model. These studies provide new understanding of the pathogenesis of gas gangrene and identified a potential therapeutic target to prevent the disease.

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.

Gas gangrene is a necrotizing infection of subcutaneous tissue and muscle that affects mainly ruminants and horses, but also other domestic and wild mammals. Clostridium chauvoei, C. septicum, C. novyi type A, C. perfringens type A, and C. sordellii are the etiologic agents of this disease, acting singly or in combination. Although a presumptive diagnosis of gas gangrene can be established based on clinical history, clinical signs, and gross and microscopic changes, identification of the clostridia involved is required for confirmatory diagnosis. Gross and microscopic lesions are, however, highly suggestive of the disease. Although the disease has a worldwide distribution and can cause significant economic losses, the literature is limited mostly to case reports. Thus, we have reviewed the current knowledge of gas gangrene in mammals.