Clostridium septicum-infected aortic aneurysm or graft is a deadly diagnosis.

BACKGROUND: Clostridium septicum is an anaerobic, motile, spore-forming, toxin-producing gram-positive bacillus that can lead to rapidly progressive gas gangrene due to the release of alpha toxin. Aortic aneurysm secondary to C. septicum infection is a rare condition with 60 cases reported in the literature; however, we have recently treated several patients with the condition in our large tertiary care and aortic center. METHODS: Blood and tissue culture results collected between January 2005 and January 2018 and maintained in the microbiology laboratory database at the Cleveland Clinic were reviewed to identify those with C. septicum reported. Each was reviewed to determine radiographic or histopathologic correlation with aortic disease. RESULTS: Seven cases of C. septicum aortitis were reviewed. Underlying malignant disease was found in four cases and a history of remote malignant disease in one case. The most common location for infection was the infrarenal abdominal aorta. Vascular surgery had previously been performed in three of the cases. Five of the seven patients underwent operative repair. All patients were treated with ß-lactam antibiotics. The two patients who did not undergo an operation died, which is consistent with the 100% mortality described in the literature. Of the five patients who underwent an operation, there was only one documented survivor and one was lost to follow-up. CONCLUSIONS: In the largest reported case series, only a small percentage of patients with C. septicum-infected aortic aneurysms survived >1 year. In the patients described, those who did not receive an operation had 100% mortality. Earlier recognition and prompt operation with appropriate antimicrobial therapy are needed to improve the outcome of patients diagnosed with this rare infection.

Clostridium perfringens α-toxin impairs granulocyte colony-stimulating factor receptor-mediated granulocyte production while triggering septic shock.

During bacterial infection, granulocyte colony-stimulating factor (G-CSF) is produced and accelerates neutrophil production from their progenitors. This process, termed granulopoiesis, strengthens host defense, but Clostridium perfringens α-toxin impairs granulopoiesis via an unknown mechanism. Here, we tested whether G-CSF accounts for the α-toxin-mediated impairment of granulopoiesis. We find that α-toxin dramatically accelerates G-CSF production from endothelial cells in response to Toll-like receptor 2 (TLR2) agonists through activation of the c-Jun N-terminal kinase (JNK) signaling pathway. Meanwhile, α-toxin inhibits G-CSF-mediated cell proliferation of Ly-6G+ neutrophils by inducing degradation of G-CSF receptor (G-CSFR). During sepsis, administration of α-toxin promotes lethality and tissue injury accompanied by accelerated production of inflammatory cytokines in a TLR4-dependent manner. Together, our results illustrate that α-toxin disturbs G-CSF-mediated granulopoiesis by reducing the expression of G-CSFR on neutrophils while augmenting septic shock due to excess inflammatory cytokine release, which provides a new mechanism to explain how pathogenic bacteria modulate the host immune system.

Oral immunization of mice against Clostridium perfringens epsilon toxin with a Lactobacillus casei vector vaccine expressing epsilon toxoid.

Clostridium perfringens type D infects ruminants and causes the enterotoxemia disease by ε-toxin. A mutated ε-toxin gene lacking toxicity was designed, synthesized, and cloned into the pT1NX vector and electroporated into Lactobacillus casei competent cells to yield LC-pT1NX-ε recombinant strain. BALB/c mice, immunized orally with this strain, highly induced mucosal, humoral, and cell-mediated immune responses and developed a protection against 200 MLD/ml of the activated ε-toxin. This study showed that the LC-pT1NX-ε could be a promising vaccine candidate against the enterotoxemia disease.

Clinical Features of Non-clostridial Gas Gangrene and Risk Factors for In-hospital Mortality.

OBJECTIVE: To examine the clinical features of patients with non-clostridial gas gangrene (NCGG) at our hospital and identify risk factors for in-hospital mortality. METHODS: This study included 24 patients with NCGG who were hospitalized in our medical facility from April 2005 to March 2015. The clinical features of NCGG were reviewed, and the characteristics of 6 patients who died in hospital and 18 who survived were compared to investigate risk factors. RESULTS: The median time from symptom onset to hospital arrival was 168 h. The causative agent was Klebsiella pneumoniae in 8.3% and mixed infection in 91.7%; 83.3% of patients had diabetes, and one patient had no obvious underlying disease. The site of infection was the neck in 4.2%, the thoracoabdominal wall and retroperitoneum in 12.5% each, the back in 33.3%, the buttocks in 25.0%, the perineum in 20.8%, and the extremities in 45.8%. Retroperitoneal infection, blood lactate ≥ 4.0 mmol/L, and Japanese Association for Acute Medicine disseminated intravascular coagulation (DIC) score ≥ 4 on emergency department (ED) arrival were significantly higher in non-survivors than in survivors. CONCLUSION: NCGG tends to develop in patients with diabetes, and in-hospital mortality rates are still high. Retroperitoneal infection, hyperlactatemia, and DIC on ED arrival are risk factors for in-hospital mortality.

Epidemiological and pathobiological profiles of Clostridium perfringens infections: review of consecutive series of 33 cases over a 13-year period.

BACKGROUND: Although Clostridium perfringens (C. perfringens) is well known as the causative agent of several forms of enteric disease, precise epidemiological and pathobiological aspects are still unknown. METHODS: We retrospectively reviewed the culture results of samples collected in our hospital from 2001 through 2013. In addition, for the detection and toxinogenic typing of C. perfringens, polymerase-chain-reaction amplification (PCR)-based rapid analysis was performed in 6 cases using DNA extracted from paraffin-embedded tissues. RESULTS: A total of 35 samples from 33 cases were positive for C. perfringens, representing an incidence of 0.017% (35/205, 114). Among 33 patients, 21 patients manifested sepsis and 7 patients had bacteremia. One of the septic cases was complicated by fatal intravascular hemolysis and thus, the prevalence was estimated at 3.0% among C. perfringens infections (1/33). The direct causative disease or state for C. perfringens infection was identified in 18 patients: surgery or intervention for cancers, 8 patients; chemotherapy for cancer, 2 patients; surgery or intervention for non-neoplastic disease, 6 patients; liver cirrhosis, 3 patients, etc. PCR-based toxinogenic typing of C. perfringens detected the alpha-toxin gene only in tissue from a patient who died of massive hemolysis; none of the toxin genes could be amplified in the other 5 cases examined. CONCLUSIONS: The prevalence of overt C. perfringens infection is low, but upon detection, infected patients should be carefully monitored for fatal acute hemolysis caused by type A C. perfringens. Furthermore, PCR-based rapid detection of C. perfringens and toxinogenic typing by archival pathological material is applicable as a diagnostic tool.

Necrotizing skin and soft tissue infections.

Necrotizing skin and soft tissue infections are severe bacterial infections resulting in rapid and life-threatening soft tissue destruction and necrosis along soft tissue planes.

Development and validation of a necrotizing soft-tissue infection mortality risk calculator using NSQIP.

BACKGROUND: Necrotizing soft-tissue infections (NSTI) are a group of uncommon, rapidly progressive infections requiring prompt surgical debridement and systemic support. A previous attempt to define risk factors for mortality from NSTI had multiple limitations. The objective of this study was to develop and validate a 30-day postoperative mortality risk calculator for patients with NSTI using NSQIP. STUDY DESIGN: The NSQIP Participant Use Files (2005-2010) were used as the primary data source. Patients diagnosed with NSTI were identified by ICD-9 codes. Multiple logistic regression analysis identified key preoperative variables predicting mortality. Bootstrap analysis was used to validate the model. RESULTS: In 1,392 identified NSTI cases, demographics were as follows: 42% were female, median age was 55 years (interquartile range 46 to 63 years), and median body mass index was 32 kg/m(2) (interquartile range 26 to 40 kg/m(2)). Thirty-day mortality was 13%. Seven independent variables were identified that correlated with mortality: age older than 60 years (odds ratio [OR] = 2.5; 95% CI 1.7-3.6), functional status (partially dependent: OR = 1.6; 95% CI 1.0-2.7; totally dependent: OR = 2.3; 95% CI 1.4-3.8), requiring dialysis (OR = 1.9; 95% CI 1.2-3.1), American Society of Anesthesiologists class 4 or higher (OR = 3.6; 95% CI 2.3-5.6), emergent surgery (OR = 1.6; 95% CI 1.0-2.3), septic shock (OR = 2.4; 95% CI 1.6-3.6), and low platelet count (<50K/µL: OR = 3.5; 95% CI 1.6-7.4; <150K/µL but >50K/µL: OR = 1.9; 95% CI 1.2-2.9). The receiver operating characteristic area was 0.85 (95% CI 0.82-0.87), which indicated a strong predictive model. Using bootstrap validation, the optimism-corrected receiver operating characteristic area was 0.83 (95% CI 0.81-0.86), which represents the model performance in future patients. The model was used to develop an interactive risk calculator. CONCLUSIONS: This risk calculator has excellent predictive ability for mortality in patients with NSTI. This simple interactive tool can aid physicians and patients in the decision-making process.

[Hyperbaric oxygen therapy for necrotizing soft tissue infections: contra]. / Hyperbare Oxygenation bei nekrotisierenden Weichteilinfektionen: Kontra.

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) is discussed as an adjuvant option to treat necrotizing soft tissue infections (NSTI). While the Federal Joint Committee decided in 2007 not to support HBOT for the indication necrotizing fasciitis and Fournier's gangrene, it was decided to accept HBOT for treatment of clostridial myonecrosis for the German health insurance. Thus, in Germany necrotizing fasciitis (NF) is not a confirmed indication for HBOT. Against this background the cons of the clinical benefits of HBOT should be formulated. METHODS: A literature search (MEDLINE/EMBASE/COCHRANE/manual search) using the keywords "necrotizing fasciitis", "Fournier's gangrene", "necrotizing cellulitis", "necrotizing soft tissue infections" as well as "hyperbaric medicine", "hyperbaric therapy" and "hyperbaric treatment" was carried out. An analysis of the spatial distribution of German hyperbaric oxygen chambers enabling intensive care (HOC-IC) was made. RESULTS: A total of 250 articles with n=2,556 NSTI patients (n=993 treated by HBOT) was found and 50% of the articles were case reports or series. There were only ten retrospective studies comparing the effects of HBOT with non-HBO treatment and none of them verified the benefit of HBOT in NF patients. In Germany only nine hyperbaric oxygen chambers (HOC-IC) enable intensive care. Currently, patient data are not included in scientific studies or multicenter studies, while studies assessing the benefit with higher evidence levels have been required for more than 15 years. CONCLUSIONS: The previously published human clinical studies do not confirm any therapeutic benefit of HBOT in NF patients. Any time delay in the start of surgical therapy by HBOT would not be acceptable. In Germany a comprehensive clinical care with HOC is not possible. On average the additional costs of HBO treatment for NF patients is approximately 8,000-25,000 /patient which is not generally reimbursed by health insurance companies. Initializing a register study to assess the benefit of HBOT in NF patients appears feasible and is urgently needed.

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.

Mortality and diabetes mellitus in amputations of the lower limbs for gas gangrene: a case report.

The aim of this study was to examine any association between the presence of diabetes in patients with gas gangrene of the legs and mortality following major lower limb amputation. In a retrospective study, patients submitted to amputation of lower limbs for anaerobic infections were evaluated in the period from January 2005 to January 2007 in the University Hospital de Base in Sao Jose do Rio Preto. All the patients were hospitalized for the treatment of ulcerated lesions of the leg. The study sample consisted of 30 men and 10 women aged between 46 and 87 years (mean 69 years) suffering from anaerobic infections. During treatment, the presence of crepitation in the skin was observed as was gas by radiological examination. Amputation was performed within 2 to 6 hours after diagnosis. Diabetes was identified in 33 patients and death occurred within the perioperative period in 12 cases. Diabetes is associated with the necessity of amputation for gas gangrene resulting in a high mortality rate.

Causes of gas gangrene seen at the University of Nigeria Teaching Hospital, Enugu, Nigeria.

Gas gangrene (clostridial myonecrosis) is rarely seen and this rarity, coupled with its dramatic presentation and often devastating outcome, makes each case of gas gangrene a spectacular and memorable experience. This study analyses the cases managed, the causes and outcome. Gunshot wounds, compounded by late presentation with its accompanying florid infections, were seen as the causes in 14 cases of gas gangrene seen at the University of Nigeria Teaching Hospital, Enugu during the four-year study period from July 2000 to June 2004.

[Complicated skin and soft tissue infections]. / Komplizierte Haut- und Weichgewebsinfektionen.

Skin and soft tissue infections are common diseases. The spectrum ranges from slight furuncles to severe necrotizing soft tissue infections. Grampositive bacteria account for 70-80 % of cases as causative organisms. Diagnostics include rapid evaluation of locally limited or diffuse spreading extent of the disease. In complicated skin and soft tissue infections, surgical intervention with debridement and necronectomy is indicated. Necrotizing skin and soft tissue infections call for programmed redebridement. If systemic signs of inflammation are present (fever > 38 degrees C, leukocytosis, CRP elevation) or significant comorbidity exists, application of antibiotics is indicated. The prognosis in operatively treated patients is dependent on the time of surgical intervention.

[Gas gangrene of the abdominal wall due to underlying GI pathology: seven cases]. / Gangrène gazeuse extensive révélant une pathologie digestive: 7 observations.

OBJECTIVE: Gas gangrene of the abdominal wall is a rare clinical occurrence with high rates of morbidity and mortality. The primary source of the infection is often unknown. To analyze the primary underlying intestinal etiologies and diagnostic approaches of gas gangrene of the abdominal wall, and to highlight specific treatment problems, particularly that of constructing a colostomy exteriorized through a massively infected abdominal wall. PATIENTS AND METHODS: Seven cases of abdominal wall gas gangrene due to a gastrointestinal etiology were identified. (Cases arising from proctologic sources or related to recent abdominal surgery were excluded.) During the same period, 39 other patients presenting with abdominal wall gangrene from non-intestinal sources were treated. RESULTS: The etiologies were: perforated sigmoid diverticulitis (n=2), perforated appendicitis (n=1), acute pancreatitis with associated cecal perforation (n=1), and perforated colorectal cancer (n=3). Four of the seven patients died despite treatment (mortality of 57%). CONCLUSION: The clinical presentations of these seven cases demonstrate that a GI source must be suspected whenever a patient presents with abdominal wall gas gangrene, even when there are no specific GI symptoms. Imaging, particularly with CT scan, is essential both to visualize the extent of tissue necrosis and to reveal underlying primary GI pathology. This optimizes the surgical approach both by allowing for complete debridement and drainage of infected tissue, and by focussing the intervention on correction of the underlying primary GI source of infection.

Heridas por asta de toro en el Hospital General de Castellón. Estudio de 387 pacientes / Bull horn wounds in Castellon General Hospital. A study of 387 patients

Las heridas por asta de toro son frecuentes en el mundo iberoamericano, donde los espectáculos con estos animales son algo habitual. Dichas heridas presentan unas características especiales que las diferencian de cualquier otro tipo de heridas. Material y método: Se realizó un estudio retrospectivo con revisión de las historias clínicas de los pacientes ingresados en nuestro servicio con el diagnóstico de herida por asta de toro entre enero de 1978 y octubre de 2005. Resultados: Se estudiaron 387 ingresos. En 12 ocasiones se trató de reingresos por nuevas cogidas en un mismo paciente. En 27 enfermos se presentaron múltiples heridas. La localización de las heridas principales fue: cabeza y cuello 12 (3,1%), tórax 21 (5,4%), extremidades superiores 19 (4,9%), abdomen 44 (11,3%), periné 41 (10,5%), región lumbar-espalda 6 (1,5%) y extremidades inferiores 244 (63%). Fueron necesarias 31 laparotomías con 23 lesiones viscerales. Aparte del tratamiento específico, se realizó lavado con solución antiséptica, Friedreich y sutura de piel sobre drenajes, tratamiento antibiótico y vacunación antitetánica. Las complicaciones inmediatas más frecuentes fueron la desvitalización de la herida y la infección, con 7 y 6 casos, respectivamente. La complicación tardía más frecuente fue la eventración con 6 casos. Hubo 3 muertes por shock hipovolémico, por shock séptico y por gangrena gaseosa. Conclusión: Las heridas por asta de toro tienen unas características propias que es necesario conocer especialmente en regiones con afición al toreo. Aunque son lesiones graves, su pronóstico es bueno, con escasas complicaciones y una mortalidad menor del 1% (AU)

Bull horn lesions are frequent in the Latin world due to spectacles involving these animals. These wounds have special characteristics that distinguish them from all other lesions. Material and method: A retrospective analysis of the medical records of patients with bull horn lesions admitted to our service between January 1978 and October 2005 was performed. Results: A total of 387 patients with bull horn lesions were admitted to our service. There were 12 readmissions due to a new wound in a previously treated patient. Twenty-seven patients had two or more lesions. The location of the wounds was: head and neck in 12 (3.1%), thorax in 21 (5.4%), upper extremities in 19 (4.9%), abdomen in 44 (11.3%), perineum in 41 (10.5%), back and lumbar region in 6 (1.5%), and lower extremities in 244 (63%). Thirty-one laparotomies were performed and there were 23 visceral lesions. Surgical treatment in addition to specific procedures consisted of irrigation with antiseptic solution, Friedreich, and primary closure over drains. Antibiotic and antitetanus vaccinations were administered in all patients. The most frequent early complications were: wound devitalization (7 patients) and infection (6 patients). The most frequent late complication was incisional hernia. Three patients died as a result of hypovolemic shock, septic shock and gas gangrene. Conclusion: Bull horn wounds have special characteristics. Familiarity with these lesions is important in areas where bullfighting is practiced. Although bull horn wounds are severe, their prognosis is good, with few complications and a mortality rate of less than 1% (AU)

Gas gangrene pyaemia with myocardial abscess formation--fatal outcome from a rare infection nowadays.

We report a case of sudden death after gas gangrene. A 67-year-old male patient with diabetes mellitus and chronic renal failure (on haemodialysis three times a week) presented in the surgical emergency department with a severe swelling and crepitation in the right groin. No signs of trauma were present-except for a well-healed, 1-year-old scar after femoro-popliteal bypass surgery. Two days earlier, he had presented to the internal medicine department with epigastric pain and had left against medical advice. On readmission the patient was initially conscious and in a stable cardiopulmonary condition but developed sudden cardiocirculatory failure and underwent resuscitation. Despite all resuscitation measures, including the administration of high doses of catecholamines and the treatment of hyperkalemia, the patient died. Autopsy revealed septicaemia with rod-shaped gram-positive bacteria, typical of Clostridium perfringens, evidenced by multiple areas of myonecrosis. Abscess formation was found in the myocardium. Clostridial gas gangrene is a rare clinical condition. Unless immediate diagnosis and adequate therapy measures are taken, the outcome and chances for survival are poor as demonstrated by this case.

Clostridial myonecrosis in horses (37 cases 1985-2000).

REASONS FOR PERFORMING STUDY: Previous reports of clostridial myonecrosis have either focused on individual case reports or have been small retrospective studies reporting very high mortality rates. OBJECTIVES: The objective of this study was to describe the outcome of cases of clostridial myonecrosis submitted to 2 referral equine hospitals in the United States over a 15 year period. METHODS: A retrospective study of case material selected on the basis of positive Clostridium spp. culture or the identification of Clostridium spp. by specific fluorescent antibody testing from soft tissue wounds was performed at Cornell and Wisconsin. RESULTS: 37 cases of clostridial myonecrosis were documented. Twenty-seven horses survived, 8 were subjected to euthanasia and 2 died during treatment for an overall survival rate of 73%. Twenty-five cases (68%) were associated with Clostridium perfringens alone, 6 cases (16%) with Cl. septicum alone, 4 cases with mixed clostridial infections (11%), 1 case with Cl. sporogenes and 1 with an unspeciated Clostridium spp. The highest survival rate of 81% was documented for those cases from which Cl. perfringens alone was isolated. The most common antecedent condition prior to referral was colic. The myonecrotic lesion occurred within 6-72 h of a soft tissue injection in 34 cases but was associated with a wound or laceration in the remaining 3 cases. Of the 34 cases associated with recent injections, 24 were associated with i.m. injections in the cervical region, 4 in the semimembranosus/semitendinosus region, 3 in the gluteal region, 2 with perivascular leakage of drugs administered into the jugular vein and 1 case developed simultaneously in the gluteal and neck region following injections at both sites. CONCLUSIONS: Clostridial myonecrosis can occur following the i.m. or inadvertent perivascular administration of a wide variety of commonly administered drugs. It is most common in the neck musculature. Aggressive treatment can be associated with survival rates of up to 81% for cases due to Cl. perfringens alone. Survival rates for other Clostridial spp. tend to be lower. POTENTIAL RELEVANCE: A combination of high dose i.v. antibiotic therapy and surgical fenestration/debridement is the best approach to cases of clostridial myonecrosis. With rapid diagnosis and therapeutic intervention, horses may have up to an 81% chance of survival.