Clostridial Infection Research Articles

Proteolytic activity of Clostridium difficile.

Ten isolates of Clostridium difficile expressing different degrees of toxigenicity and virulence in an animal model were assayed for the production of proteolytic enzymes by various methods. All strains demonstrated some activity in one or more of the assay systems. There was no direct correlation between toxigenic status and enzyme production. However, those strains known to be highly virulent in a hamster model were the most proteolytic. The most commonly detected enzyme was cell associated, and its substrate specificity suggested it was a trypsin-like enzyme. Initial purification of the enzyme from strain VPI 10463 gave a 10% yield with a 14-fold increase in purity. Inhibition studies on this preparation indicated that the enzyme was a thiol protease. The enzyme has pH and temperature optima of 7.5 and 37 degrees C, respectively. These characteristics suggest that the enzyme is more related to clostripain, the thiol clostridio-peptidase of C. histolyticum, than to trypsin. Whilst the role of this enzyme remains unclear, it is possible that it may be a contributory factor in the virulence of the organism as described for other clostridial infections.

Bacteriological investigation of sudden sheep mortality in Morocco

A bacteriological examination was made of samples from 128 cases of sudden death in sheep from 18 farms for the presence of important bacterial pathogens. Clostridial infections were present in 43 sheep (33.6%), colisepticemia in 24 (18.8%), septic pasteurellosis in 11 (8.6%), other septicemias in 10 (7.8%), 4 (3.1%) had unidentified bacterial infections, and 36 (28.1%) had no important bacteria. Clostridium perfringens types C and D accounted for 35 (34.0%) of isolates, Clostridium sordellii for 14 (13.6%), Clostridium septicum for 4 (3.9%). Escherichia coli (serotypes 078, 0144, 036, 075) accounted for 25 (24.3%) isolates, Pasteurella haemolytica for 11 (10.7%), Streptococcus spp. for 5 (4.8%), Staphylococcus aureus for 3 (2.9%), Actinomyces pyogenes for 2 (1.9%), and unidentified Gram-negative rods for 4 (3.9%). Clostridium sordellii alone or with C. perfringens may be an important pathogen in sudden mortality in sheep since it was recovered from 14 out of 128 sheep. Of 43 sheep with clostridial infections, 17 were vaccinated with a multicomponent vaccine ( C. perfringens types A, B and D, C. septicum and C. novyi) and 26 were unvaccinated animals. These findings indicate the need for improved vaccines or vaccination programs.

Clostridial Infection as a Cause of Fulminant Congenital Sepsis Neonatorum

Clostridial Infection as a Cause of Fulminant Congenital Sepsis Neonatorum

Total Perineal Reconstruction After Major Obstetrical Injuries with Extensive Tissue Loss: A Report of 2 Cases

Major perineal injuries following obstetrical complications represent difficult problems of reconstruction. We describe 2 such patients with perineal injuries simulating infantile cloacas. Surgical repair using an abdominoperineal pullthrough procedure in 1 patient, and a Bricker loop type of repair in another resulted in successful restoration of function in both. The operative details and basis for the reconstruction are described.

Successful antibiotic therapy of clostridial septic arthritis in a patient with bilateral total hip prostheses

We report a case of clostridial bacteraemia with infection of a prosthetic hip joint. The patient was successfully treated with IV benzyl penicillin and fucidin followed by oral amoxycillin and probenecid, without surgical intervention. She had no recurrence of her infection in the 19 months before her death. This is believed to be the first reported case of clostridial infection affecting a prosthetic joint.

Treatment and control of an outbreak of fat cow syndrome in a large dairy herd

An outbreak of fat cow syndrome occurred in a herd of 300 Friesian and Friesian/Holstein dairy cows calving predominantly between January and May. The herd came in off grass in good condition despite a long and hot summer. The dry cows received a diet of grass silage, brewing waste and minerals until the end of December, but the grass silage was butyric and was partially replaced by maize silage. By January 23, 16 of 70 calving cows (23 per cent) had appeared to suffer milk fever. Subsequent blood tests revealed that the cows may have been ketotic, and clinical and post mortem examination showed that they were probably suffering from fat cow syndrome. The freshly calved sick cows were treated with glucose, and corticosteroids were injected every second day into those which remained ill. The cattle had received a high energy diet, but the cows still to calve were placed on a diet of low metabolisable energy (77 MJ/cow) but adequate levels of undegradable protein. The problem was associated with a possible clostridial infection in two cows and with reduced fertility.

Mycotic Aortic Aneurysm Infected by Clostridium septicum — A Case History

The authors describe a sixty-seven-year-old hypertensive, diabetic man with a mycotic abdominal aortic aneurysm infected with Clostridium septicum. The patient had colonic polyps but no malignant disease. They could find only one other report of a mycotic aneurysm infected with C. septicum. In that case, as in most other cases of C. septicum bacteremia, the patient had gastrointestinal cancer. Their case suggests that treatment for a clostridial infection should be considered in patients with known gastrointestinal disease, signs and symptoms of sepsis, and abdominal pain. Conversely, patients known to have a C. septicum infection should be evaluated for gastrointestinal lesions.

The GP contract

The case is described of a 68 year old man who was immunosuppressed as a result of receiving chemotherapy for small cell lung cancer and who presented with severe right thigh pain. This proved to be due to clostridial myonecrosis with none of the classical clinical features of clostridial infection. This is believed to be the first reported case of spontaneous clostridial infection associated with etoposide administration.

Application of sialidase antibodies for the diagnosis of clostridial infections

Two immunological methods, a sialidase-inhibition test and an ELISA, had been developed for a species-specific detection of sialidases (EC 3.2.1.18) secreted by growing cells of Clostridium perfringens, C. septicum, and C. sordellii. These assays were applied to samples from the infected tissues and cotton wool plugs soaked with wound exudate from patients suspected to be suffering from gas gangrene. The results from 72 patients were compared with bacteriological investigations of 67 homologous samples. From these, 35 patients were found to be infected with one or two of the clostridial species: thirty patients contained C. perfringens, six samples showed an immunologically positive reaction for C. septicum and eight for C. sordellii. In the case of C. perfringens, a high degree of coincidence between the immunological and the bacteriological analyses was obtained. However, in infections with C. septicum or C. sordellii the bacteriological and immunological tests did not agree well. The simple and rapid sialidase inhibition test or the slightly more time-consuming ELISA, which even detects low quantities of sialidase, can be applied for the specific diagnosis of infections caused by C. perfringens, thus allowing a species-specific detection of this bacterial species in two or six hours, respectively, even at an early stage of infection. This early diagnosis is a prerequisite for a specific and life-saving therapy of this severe disease.

Clostridial infection of a locally recurrent renal cell carcinoma with sepsis

An association between clostridial sepsis and malignancy is well established in the literature. Although anaerobes are a relatively infrequent cause of renal abscess, there have been recent reports of anaerobic abscesses occurring in renal tumor masses. The present report describes a case of sepsis due to Clostridium perfringens infection of a locally recurrent renal cell carcinoma. The infection may have originated either from tumor invasion of the adjacent bowel or by hematogenous seeding of the mass at the time of colonoscopy. Patients with bulky, necrotic tumors who have invasive diagnostic procedures relating to either the gastrointestinal or urogenital tracts, as well as those having malignancies involving these systems, are at increased risk of infection with bowel anaerobes. Clostridial abscesses with accompanying sepsis occur in this setting, and empiric antibiotic regimens should include coverage for these organisms. Early, aggressive surgical intervention is essential.

Clostridial pleuropulmonary infections: Case report and review of the literature

Clostridia rarely cause pleuropulmonary infections in the absence of trauma. We report a case of intermittent bowel obstruction, clostridial bacteraemia and pneumonia with a fatal outcome. Only 16 cases have previously been reported. Clostridial infection of the lung has many features of an acute pneumonia and is almost always associated with a pleural effusion. Most cases are caused by Clostridium perfringens, though infections with other species have been reported. The prognosis is generally more favourable than in clostridial infection secondary to aspiration pneumonia or complicating empyema.

Antibiotic prophylaxis in lower-extremity amputations due to ischemia

The efficiency of prophylactic antibiotic therapy in amputation surgery was studied in a prospective, randomized trial of a first-generation cephalosporin (cephalothin) compared with a narrow-spectrum beta-lactam stable penicillin (methicillin). Eighty-eight patients received cephalothin 2 g X 4 on the day of operation, while 86 patients received methicillin 1 g X 4. The patients were followed up for 21 days. Infected wounds occurred in 14.8% of the patients in the cephalothin group, compared with 14% in the methicillin group. The frequency of deep infections was 10.2% versus 4.7% (P = 0.1611). The reamputation frequency was 18.2% in the cephalothin group compared with 12.8% in the methicillin group; the frequency of below-knee reamputation was 18.4% versus 7.7% (P = 0.1469). No clostridial infections were found. The study did not demonstrate any significant difference between cephalothin and methicillin in the prophylaxis for lower-extremity amputations, although the latter drug tended to be the best choice.

Transfusion of infants with activation of erythrocyte T antigen

A protocol for transfusion of infants with erythrocyte T-antigen activation was evaluated for safety and effectiveness in a prospective, 3-year, sequential series of 1672 infants admitted for intensive care. Erythrocyte T antigens are activated by enzymes produced by clostridia or other bacteria in infants with sepsis, often in association with necrotizing enterocolitis. Transfusion of these infants with blood products containing plasma carries the risk of causing intravascular hemolysis. Our transfusion protocol included testing for T-antigen activation, restricting transfusion of patients with activated T antigens to washed erythrocytes or washed platelets whenever possible, and selecting donors with low-titer anti-T when plasma-containing blood products were required. In this series, 10 patients had T-antigen activation, including four with clostridial infections. Severe hemolysis occurred in one patient who received plasma before T-antigen activation developed. Of five patients who received low-titer anti-T plasma, mild hemolysis occurred in three and no hemolysis in two. Four patients who received no plasma-containing blood products experienced no hemolysis. Used cautiously, this protocol allows a full range of transfusion therapy to infants with T-antigen activation.

Komplikationen nach Zelltherapie

So far, the law in the Federal Republic of Germany still allows the injection of fresh-cell preparations from animals as a roborant to increase the vitality of the organism and to strengthen the body's immune defense system. The use of "sicca-cell" preparations was provisionally forbidden in 1987 by the Federal Health Organization (Bundesgesundheitsamt; BGA). Prohibition of fresh-cell injections would have exceeded the authority of this office, although the same serious reservations also applied in the case of this treatment method. Several publications that have appeared since 1955 have reported serious complications of this therapy, some life-threatening and some even lethal. Two further cases are now added: (1) A woman aged 69 had been receiving treatment with cell injections for 9 years. Immediately after an injection of sicca cells she collapsed and was hospitalized; 7 days thereafter she developed an ascending paralysis with increasing inability to swallow or breathe. She died 25 days after the injection as a consequence of central and peripheral respiratory failure. Autopsy revealed the alterations typical for acute Landry-Guillain-Barré-Strohl syndrome. (2) A 76-year-old healthy woman had been receiving treatment with fresh-cell preparations for several years. After an injection of cell suspensions a painful local swelling was observed. The symptoms were interpreted as the consequence of an iatrogenic local hematoma, and repeated punctures were performed to obtain blood. The patient was transferred to a surgical department for further therapy. Two days after the injection she suddenly died with signs of acute cardiovascular failure. Autopsy revealed the signs of a fulminating clostridial infection and also the characteristic signs of Landry-Guillain-Barré syndrome with involvement of the autonomic nervous system. In both cases the development of an inflammatory process in the peripheral nervous system could be interpreted as an immune-mediated allergic disease, related to the repeated injection of heterologous antigenic material containing nervous tissues. This hypothesis would also explain the two other cases already published and would be consistent with the observed perivenous leukoencephalopathy of the central nervous system. The human disease pictures correspond to the well-established animal models of EAEM (experimental allergic encephalomyelitis) and EAN (experimental allergic neuritis). The pathogenesis is discussed; the major role of the central and peripheral nervous system is stressed, with special reference to the risk of acute autonomic failure. The need for specific autopsy techniques for the investigation of the entire nervous system, including spinal cord, roots, spinal ganglia and peripheral nerves with sympathetic chains, is raised.

Clostridium perfringens infection in a total knee arthroplasty : A case report

A 66-year-old woman with a painful total knee arthroplasty and turbid fluid aspirates had her prosthesis removed for a presumed diagnosis of infection. The intraoperative cultures were positive for Clostridium perfringens, and the patient did well after a course of intravenous antibiotics prior to reimplantation. Clostridium perfringens is a rare cause of pyarthrosis in both non-operative and prosthetic joints. This report details the first case of clostridial infection involving a patient with a total knee arthroplasty.

Occult gastrointestinal carcinoma causing metastatic clostridial soft-tissue infection

The association between nontraumatic, metastatic, clostridial soft-tissue infection and malignancy is well recognized, particularly when Clostridium septicum is involved. This report presents two patients with nontraumatic, metastatic, soft-tissue infection due to C. septicum and reviews the English medical literature. Eighty-four percent of the reported patients were found to have colon carcinoma, which was postulated to be the portal of entry. Prognosis is poor, but early recognition and antimicrobial therapy with prompt and aggressive surgical intervention, both for the soft-tissue infection and the abdominal process, may lower the high mortality.

Early diagnosis of clostridial gas gangrene using sialidase antibodies

In order to improve the diagnosis of gas gangrene, especially at an early stage of infection, new ways for the detection of the responsible Clostridia were investigated. Sialidase, known to be excreted in large amounts by the most frequently occurring myonecrotizing clostridial species, Clostridium perfringens, Clostridium septicum, and Clostridium sordellii, was isolated. With polyclonal antibodies raised against these enzymes, two immunological assays were established, which are directed against the sialidase activity (sialidase inhibition test) and the enzyme protein (‘sandwich’-ELISA), respectively. Using these assays, species-specific information about the presence of clostridial sialidase was obtained within 50 min or 6 h. Animal tests revealed that both assays are applicable 8–12 h after clostridial infection, using resected tissues or wound fluids for estimations. The assays allow specific, sensitive, and quantitative measurement of clostridial sialidases, and no significant interference by sialidases from other microbes or from host tissues occurred. The applicability of the new assays for an early diagnosis of gas gangrene in human patients is discussed.

Overwhelming infections in trauma.

Following trauma, wound contamination with aerobic and/or anaerobic bacteria should always be suspected. Treatment with antibacterial antibiotics should begin immediately in the emergency room, particularly for those patients with fractures. Patients with serious trauma are best treated by a team of specialists including general surgeons, orthopedists, infectious disease specialists, and intensive care specialists. The author recommends transport of seriously injured patients to major hospitals specializing in the care of trauma. Particularly when gas gangrene secondary to clostridial infection is suspected, the patient should be moved to a major trauma center with the capability for hyperbaric oxygen therapy.

Endogenous Clostridium Panophthalmitis

Acute visual loss, pain, and redness in the left eye developed in a 61-year-old diabetic man. Results of ophthalmologic examination showed 4+ conjunctival hyperemia and chemosis, no light perception, and restricted ocular motility. Through a hazy cornea, a gas bubble was visualized filling about 50% of the anterior chamber. A vitreous tap disclosed myriad gram-positive rods with terminal and subterminal spores. Cultures of the vitreous grew Clostridium septicum, a gas-forming organism. Exploratory abdominal laparotomy showed a ruptured diverticulum of the sigmoid colon with acute peritonitis. In spite of intensive antibiotic therapy, the patient died approximately 24 hours after admission. Results of histopathologic examination of the postmortem left eye demonstrated massive necrosis of the intraocular structures with numerous gram-positive rods confined mainly to the retinal pigment epithelium (RPE), detached retina, and vitreous. To the best of the authors' knowledge, this is the second reported case of C. septicum panophthalmitis. Only 69 cases of clostridial infections with ocular involvement have been recorded previously in the literature.

Rapid presumptive diagnosis clostridial infections by gas chromatography.

Gas chromatography (GC) was tried for rapid presumptive diagnosis of clostridial infection in domestic animals. Propionic, butyric, and acetic acids were detected by GC in specimens collected from lesions in the liver and spleen of a pig died of gas gangrene. The volatile fatty acid (VFA) pattern was very similar to that of a culture of Clostridium novyi isolated from these lesions. Emulsions of the lesions in the liver and spleen of the two cows died of blackleg exhibited VFA patterns resembling that of a culture of Clostridium chauvoei isolated from these lesions. The results of GC analyses of subcutaneous lesions of mice and guinea pigs experimentally infected with C. novyi and those with C. chauvoei were very similar to those of the pig and the cows, respectively. The VFA pattern of lesions of domestic animals may be useful for rapid presumptive diagnosis of a certain clostridial infections such as that with C. novyi. It may be difficult, however, to distinguish among infections with Clostridium tetani, Clostridium septicum, and C. chauvoei by GC analysis.