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Reduced tissue perfusion leading to tissue ischemia is a central component of the pathogenesis of myonecrosis caused by Clostridium perfringens. The C. perfringens alpha-toxin has been shown capable of inducing these changes, but its potential synergy with perfringolysin O (theta-toxin) is less well understood. Similarly, Clostridium septicum is a highly virulent causative agent of spontaneous gas gangrene, but its effect on the microcirculation has not been examined. Therefore, the aim of this study was to use intravital microscopy to examine the effects of C. perfringens and C. septicum on the functional microcirculation, coupled with the use of isogenic toxin mutants to elucidate the role of particular toxins in the resultant microvascular perfusion deficits. This study represents the first time this integrated approach has been used in the analysis of the pathological response to clostridial toxins. Culture supernatants from wild-type C. perfringens induced extensive cell death within 30 min, as assessed by in vivo uptake of propidium iodide. Furthermore, significant reductions in capillary perfusion were observed within 60 min. Depletion of either platelets or neutrophils reduced the alteration in perfusion, consistent with a role for these blood-borne cells in obstructing perfusion. In addition, mutation of either the alpha-toxin or perfringolysin O structural genes attenuated the reduction in perfusion, a process that was reversed by genetic complementation. C. septicum also induced a marked reduction in perfusion, with the degree of microvascular compromise correlating with the level of the C. septicum alpha-toxin. Together, these data indicate that as a result of its ability to produce alpha-toxin and perfringolysin O, C. perfringens rapidly induces irreversible cellular injury and a marked reduction in microvascular perfusion. Since C. septicum induces a similar reduction in microvascular perfusion, it is postulated that this function is central to the pathogenesis of clostridial myonecrosis, irrespective of the causative bacterium.

Background Clostridium septicum is a rare cause of meningitis and brain abscess in children and adults. Gas production by the pathogen can lead to pneumocephalus and the overall mortality rate of Clostridium septicum CNS infection is as high as 74%. The most common entry site of the pathogen is the gastrointestinal tract. Case presentation We describe a 74-year-old man who presented with a left-sided cerebral infarction in the middle cerebral artery territory. In addition the patient showed signs of Systemic Inflammatory Response Syndrome and Disseminated Intravascular Coagulation. Examination of blood cultures and cerebrospinal fluid led to the diagnosis of sepsis and meningitis caused by Clostridium septicum . Despite appropriate antibiotic therapy the condition of the patient deteriorated rapidly and he died on day 2 after admission. Autopsy revealed a previously unknown adenocarcinoma of the colon ascendens as entry site of the pathogen. Conclusion Clostridium septicum should be considered as potential pathogen in patients with sepsis and meningitis. Gram stain morphology in conjunction with severe sepsis can rapidly point into the direction of this pathogen. CNS infections manifest either as meningoencephalitis/cerebritis or as brain abscess. Entry site of the pathogen is almost uniquely the gastrointestinal tract. In adults more than 50% suffer from colorectal carcinoma, therefore survivors of Clostridium septicum infections should be examined for underlying occult colorectal malignancy.

Background Spontaneous pneumocephalus in the nontraumatic setting is distinctly unusual. Pneumocephalus from central nervous system infection with Clostridium septicum has been rarely reported, and more commonly reflects a later stage of abscess formation. We present an unusual case of invasive C. septicum infection without an associated diagnosed malignancy presenting with rapidly progressive CNS pathology and resultant early pneumocephalus. Methods Medical records, radiologic imaging, and microbiological specimens of a case were reviewed. Results A 66-year-old male presented with a history of two witnessed generalized tonic–clonic seizures on awakening. He was found unresponsive at the scene by paramedics and subsequently intubated. There was no reported antecedent symptomatology, such as headache, fever, chills, focal weakness, and speech or gait disturbances. Medical history was remarkable only for diet-controlled hypertension. Computed tomography (CT) head imaging revealed an abnormal right parietal hypodensity. The patient was evaluated per the acute stroke protocol but was not deemed a candidate for intervention or thrombolytic therapy given the uncertainty of his clinical presentation; intravenous antibiotics were administered for possible sepsis. Follow-up CT imaging of the head performed 8 h later revealed right parieto-temporal pneumocephalus with extensive cerebral edema and effacement of basilar cisterns. Neurosurgical intervention was not deemed appropriate given the catastrophic nature of his injury and the patient subsequently expired 14 h after presentation. Blood cultures grew gram-positive rods in three of four bottles identified as C. septicum . Conclusions Clostridium septicum is an uncommon and often fatal cause of nontraumatic pneumocephalus. This underscores the need for a high index of clinical suspicion in cases with unexplained pneumocephalus, as early diagnosis remains the key to survival. In survivors of C. septicum infection, subsequent colonoscopy should be considered to exclude undiagnosed or occult gastrointestinal malignancy.

The long-term use of proton pump inhibitors has been linked to an increased risk for the development of gastric polyps, hip fractures, pneumonia, and Clostridium difficile colitis. There is evidence that chronic acid suppression from long-term use of proton pump inhibitors poses some risk for the development of C difficile –associated diarrhea by decreasing the elimination of pathogenic microbes before reaching the lower gastrointestinal tract. Here we present a case of a 51-year-old woman with a recent history of abdominal pain and fever who presented to the emergency department with rapidly progressive spontaneous necrotizing fasciitis and gas gangrene and died within hours of presentation. Postmortem examination confirmed spreading tissue gas gangrene and myonecrosis. In addition, multiple intestinal ulcers containing Clostridium septicum were present at autopsy. This case illustrates a possible association between proton pump inhibitor therapy and fatal C septicum infection.

Clostridia produce the highest number of toxins of any type of bacteria and are involved in severe diseases in humans and other animals. Most of the clostridial toxins are pore-forming toxins responsible for gangrenes and gastrointestinal diseases. Among them, perfringolysin has been extensively studied and it is the paradigm of the cholesterol-dependent cytolysins, whereas ε-toxin and αα-toxin, which are related to aerolysin, are the prototypes of clostridial toxins that form small pores. Other toxins active on the cell surface possess an enzymatic activity, such as phospholipase C and collagenase, and are involved in the degradation of specific cell-membrane or extracellular-matrix components. Three groups of clostridial toxins have the ability to enter cells: large clostridial glucosylating toxins, binary toxins and neurotoxins. The binary and large clostridial glucosylating toxins alter the actin cytoskeleton by enzymatically modifying the actin monomers and the regulatory proteins from the Rho family, respectively. Clostridial neurotoxins proteolyse key components of neuroexocytosis. Botulinum neurotoxins inhibit neurotransmission at neuromuscular junctions, whereas tetanus toxin targets the inhibitory interneurons of the CNS. The high potency of clostridial toxins results from their specific targets, which have an essential cellular function, and from the type of modification that they induce. In addition, clostridial toxins are useful pharmacological and biological tools.

The role of Clostridium perfringens and Clostridium septicum in the development of cellulitis and mortality in turkey poults was examined. Studies were done in turkeys of two age groups: 3-wk-old and 7-wk-old turkey poults. The effect of varying doses of C. perfringens and C. septicum in reproducing cellulitis lesions and mortality in turkeys was investigated. Both in vitro and in vivo assays were conducted to study their toxic and biologic activities. Clostridium septicum spore culture was found to be more potent than that of C. perfringens in both in vitro assays, such as the hemolysis test, and in vivo assays in mice and turkeys. Both C. perfringens and C. septicum spore cultures were found to be capable of inducing cellulitis lesions and mortality in turkey poults when inoculated by subcutaneous route. Histopathology examination of affected tissues revealed a “moth-eaten appearance,” with abundant growth of C. perfringens and C. septicum in the sarcomeres of muscle tissues and in the subcutaneous tissues. However, C. septicum was found to be more potent than C. perfringens in causing cellulitis lesions and mortality in turkeys. Three-week-old poults were found to be less susceptible than 7-wk-old poults in the development of cellulitis lesions and mortality after inoculation with either spore cultures of C. perfringens or C. septicum. The results of the current study suggest that although C. septicum is more potent in causing cellulitis lesions and mortality, infection with either C. septicum or C. perfringens can cause cellulitis lesions and mortality in turkeys.

A gangrenous dermatitis model was developed in broiler chickens, in which birds previously vaccinated at 14 days of age with a bursal disease virus vaccine were challenged at 4 wk of age with various bacterial combinations with the combination of subcutaneous and intramuscular injection. Gangrenous dermatitis lesions were not produced in birds injected with one of the Staphylococcus aureus isolates, either alone or in combination with various Clostridium septicum isolates. Other S. aureus isolates produced significant levels of gangrenous dermatitis either alone or in combination with the same C. septicum isolates. These same C. septicum isolates when given alone did not produce gangrenous lesions. Data from this experiment show the highest level of mortality occurred in birds challenged with a mixture of C. septicum and S. aureus isolates, whereas lower or no mortality was associated with the same isolates given separately. The data clearly demonstrate that the pathogenicity of isolates responsible for gangrenous dermatitis varies widely, indicating that the frequency and severity of lesion production, as well as the occurrence of mortality, are largely dependent upon the specific isolate or isolates with which the birds are challenged.

Clostridium septicum bacteremia typically portends a fulminant disease associated with high mortality. We describe the clinical courses of seven survivors of C. septicum infection and their antibody responses to the a toxin produced by C. septicum. Three patients had clinical syndromes ranging from uncomplicated bacteremia to early typhlitis, and three patients had syndromes ranging from abscess to myonecrosis and septic shock. In addition, an AIDS patient who developed septic shock and who had extensive gas in the retroperitoneal musculature did not undergo surgery but survived after receiving antimicrobial therapy and intensive supportive care. Both immunocompetent patients with myonecrosis had detectable IgG to α toxin by immunoblot analysis. IgG to α toxin was not detected in the four immunocompetent patients who had C. septicum bacteremia but who did not have myonecrosis or in the AIDS patient with myonecrosis. Therefore, humoral responses to α toxin during C. septicum infection may be related to the host's clinical syndrome and immune status.

An adult female bearded vulture (Gypaetus barbatus) in the Tel Aviv University Research Zoo was found dead without previous clinical signs. The predominant pathologic changes were considerable bloody content in the intestines and enlargement of the liver, which had a rubbery consistency with color changes. Microscopic lesions consisted of multifocal histiocytic infiltration in the liver. Newcastle disease virus (NDV) was isolated from a cloacal swab and from the lungs and liver. Intracerebral pathogenicity index of the virus, as estimated in 1-day-old chicks, was repeated three times and had an average value of 1.68, indicating a velogenic strain. Numerous Clostridium septicum bacteria were found on the intestinal surface, but bioassays in which they were orally administered into chickens and mice revealed that, even though they were heavily multiplied in the intestines, they were nonpathogenic. It seems that NDV, documented for the first time in a bearded vulture in Israel, was the likely cause of sudden death.

In this study we attempted to determine the effect of temperature and glucose concentration on DNase production by C. septicum. The results showed an enhancement of DNase activity of the supernatants obtained with limitation of the carbon source, where activity was high at a dilution of 1:50 (72%) and partially conserved at a dilution of 1:100 (23%), whereas no DNase activity was detected in batch conditions at the same dilutions. The final biomass almost increased 2.5 times under carbon limitation. Temperature affected DNase activity of C. septicum 3606 undiluted supernatants as follows: 66%, 71%, 87%, and 41% at 22 degree C, 30 degree C, 37 degree C, and 41.5 degree C, respectively. The activities of C. septicum 3606 and C. septicum ATCC 12464 were similar at 37 degree C. DNase activity diminished by 21% when supernatants were stored at -20 degree C for 24 hours.