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    A genetically engineered vaccine against the alpha-toxin of Clostridium perfringens protects mice against experimental gas gangrene
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    Gas gangrene caused by Clostridium species is a long-recognized complication of trauma and penetrating intra-abdominal wounds. Spontaneous gas gangrene in the absence of trauma is nearly always described as occurring in patients with underlying diseases. While Clostridium perfringens is the cause of trauma-related gas gangrene in 60–80% of cases, spontaneous myonecrosis is typically caused by Clostridium septicum.1Kaiser C.W. Milgrom M.L. Lynch J.A. Distant nontraumatic clostridial myonecrosis and malignancy.Cancer. 1986; 57: 885-889Crossref PubMed Scopus (21) Google Scholar Here we describe a patient with fulminant spontaneous C. perfringens gangrene, in febrile neutropenia, with the characteristic histopathologic changes. A previously healthy 52-year-old male presented to the Emergency Department complaining of right lower quadrant pain and fever. His medical history was significant only for upper respiratory tract infection symptoms and oral aphthous lesions for the previous week. On examination, the patient appeared anxious. His temperature was 39 °C, blood pressure 140/75 mmHg, pulse rate 100/minute and respiration rate 24/minute. The physical examination revealed no abnormality. The laboratory evaluation was within normal limits with the exception of the following values: WBC count 2.5 × 109/L with 5% neutrophils, hemoglobin 8.6 g/dL, hematocrit 24%, RBC count 2.5 × 1012/L. The serum glucose was 193 mg/dL. The prothrombin time was 38.6 seconds with 69.1 seconds partial thromboplastin time. C-reactive protein (CRP) was 22.3 mg/dL. The patient was hospitalized; ceftazidime plus amikacin was started as our empirical first line therapy for febrile neutropenia. On the second day of therapy the patient complained of severe pain in the right dorsal aspect of his thigh and developed hypothermia. He was transferred to the ICU with hypotension, hypothermia, and oliguria. Though he remained conscious and oriented, oxygen therapy was started (10 L/min). When a single bulla was noted on the right shoulder, intravenous metronidazole was added to the previous regime. Within 3 hours he developed abdominal erythema with swelling throughout the right hemithorax and right leg including the scrotum. Subcutaneous crepitation was detected throughout the right side of the body with the appearance of blue-black bullous lesions containing watery fluid (Figure 1). X-Ray films revealed gas in the soft tissues of right side of the body. Despite all measures, including bicarbonate with dopamine and noradrenaline infusion, he remained unresponsive to therapy. An exploratory fasciotomy revealed vascular thrombosis with no bleeding in fascial planes and muscle, establishing the clinical diagnosis of myonecrosis. Since his condition was inoperable, only material from blisters was examined histopathologically and bacteriologically. Gram and Giemsa smears contained Gram-positive rods with a few WBCs, and anaerobic cultures yielded Gram-positive rods with double hemolysis zones. The bacteria were non-motile and identified with an enzymatic biochemical system (BBL; Crystal, Atlanta, GA) as C. perfringens. Histological examination showed marked myonecrosis with visualisation of Gram-positive bacterial invasion within muscle and along fascial planes. Despite all supportive measures, the patient died of multiorgan failure with progressive hypotension within 4 hours of admission to ICU. In a review of the literature, 49% of gas gangrene cases were found to occur in patients after injury and 35% after surgery.2Rai R.K. Londhe S. Sinha S. Campbell A. Aburiziq I.S. Spontaneous bifocal Clostridium septicum gas gangrene.J Bone Joint Surg Br. 2001; 83B: 115-116Crossref Scopus (20) Google Scholar It occurred spontaneously in only 16% of cases and this form is typically caused by C. septicum.1Kaiser C.W. Milgrom M.L. Lynch J.A. Distant nontraumatic clostridial myonecrosis and malignancy.Cancer. 1986; 57: 885-889Crossref PubMed Scopus (21) Google Scholar, 3Stevens D. Musher D. Watson D. Eddy H. Hamill R. Gyorkey F. et al.Spontaneously nontraumatic gangrene due to Clostridium septicum.Rev Infect Dis. 1990; 12: 286-296Crossref PubMed Scopus (182) Google Scholar, 4Zelic M. Vukas D. Vukas Jr., D. Valkovic P. Kovac D. Sustic A. et al.Fulminant endogene gas gangrene in a previously healthy male.Scand J Infect Dis. 2004; 36: 388-389Crossref PubMed Scopus (5) Google Scholar Although C. perfringens is the most common cause of gas gangrene, C. septicum is the dominant species associated with malignancy, diabetes mellitus, and immunosuppression.5Hausmann R. Albert F. Geissdorfer W. Betz P. Clostridium fallax associated with sudden death in a 16-year-old boy.J Med Microbiol. 2004; 53: 581-583Crossref PubMed Scopus (14) Google Scholar, 6Carron P. Tagan D. Fulminant spontaneous Clostridium septicum gas gangrene.Ann Chir. 2003; 128: 391-393Crossref PubMed Scopus (4) Google Scholar, 7San Ildedefonso A. Maruri I. Facal C. Casal E. Clostridium septicum infection associated with perforation of colon diverticulum.Rev Esp Enferm Dig. 2002; 94: 361-366PubMed Google Scholar, 8Garcia-Suarez J. de Miguel D. Krsnik I. Barr-Ali M. Hernanz N. Burgelata C. Spontaneous gas gangrene in malignant lymphoma: an underreported complication?.Am J Hematol. 2002; 70: 145-148Crossref PubMed Scopus (15) Google Scholar, 9Pritchett J.W. Spontaneous bifocal Clostridium septicum gas gangrene.J Bone Joint Surg Br. 2001; 83: 621PubMed Google Scholar It is believed that Clostridia gain access to the bloodstream after colonising the mucosa of the large bowel,10Corey E.C. Nontraumatic gas gangrene. Case report and review of emergency therapeutics.J Emerg Med. 1991; 9: 431-436Abstract Full Text PDF PubMed Scopus (29) Google Scholar then spread via the bloodstream to skeletal muscle, causing myonecrosis. Risk factors for development of nontraumatic gas gangrene include intramuscular injections, malignancy, immunosuppression, and colonoscopy or neutropenic enterocolitis.9Pritchett J.W. Spontaneous bifocal Clostridium septicum gas gangrene.J Bone Joint Surg Br. 2001; 83: 621PubMed Google Scholar, 11Pitt M. Purser N. Gas gangrene.Lancet. 1996; 347: 1116-1117Abstract PubMed Google Scholar, 12Keogh G. Unsworth I. Vowels M. Kern I. Spontaneous Clostridium septicum myonecrosis in congenital neutropenia.Aust NZ J Surg. 1994; 64: 574-575Crossref PubMed Scopus (13) Google Scholar, 13Jacob Z.C. Dedekian M. Seoudi H. Nontraumatic clostridial myonecrosis: an indication for colonoscopy?.Am Surg. 2002; 68: 463-465PubMed Google Scholar Our patient developed all typical features of clostridial myonecrosis, with neutropenia as a risk factor at the time. The onset of disease is typically abrupt with extraordinary or excruciating pain. On admission of the patient this pain was overlooked. Rapid progression of gangrene followed. The planned bone marrow biopsy was cancelled due to transfer to ICU. The radiological examination revealed no abnormality. When gas gangrene is clinically diagnosed debridement should not be delayed but since the lesion in this patient began on the inner side of the right shoulder and rapidly progressed to the hemithorax, his condition was evaluated as inoperable. Only an explorative fasciotomy could be done for diagnostic purposes. Necrotizing enterocolitis has also been described recently in patients with C. septicum sepsis and neutropenia.14Katlic M.R. Derkac W.M. Coleman W.S. Clostridium septicum infection and malignancy.Ann Surg. 1981; 193: 361-364Crossref PubMed Scopus (84) Google Scholar, 15Narulo A. Khatib R. Characteristic manifestations of clostridium induced spontaneous gangrenous myositis.Scand J Infect Dis. 1985; 17: 291-294PubMed Google Scholar, 16Rifkin G.D. Neutropenic enterocolitis and Clostridium septicum infection in patients with a granulocytosis.Arch Intern Med. 1980; 140: 834-835Crossref PubMed Scopus (67) Google Scholar Rifkin16Rifkin G.D. Neutropenic enterocolitis and Clostridium septicum infection in patients with a granulocytosis.Arch Intern Med. 1980; 140: 834-835Crossref PubMed Scopus (67) Google Scholar suggested that mucosal ulceration associated with neutropenia can become colonized with clostridial species. In our case although neutropenia was present, autopsy could not be performed, hence enterocolitis could not be exluded. It has not, however, been shown that clostridial species can be isolated with increased frequency from feces of patients with colonic lesions or neutropenia. Despite a rapid and usually fatal clinical course, leading to death within 12–24 hours, cures have been reported following prompt administration of high dose antibiotics and surgical debridement.17Salanitri G.C. Tauro P.G. Clostridium septicum septicemia with myonecrosis.Australas Radiol. 1999; 43: 256-259Crossref PubMed Scopus (9) Google Scholar As a result, patients with suspected gas gangrene who are in severe pain should be given urgent treatment to maximise the chances of survival. Conflict of interest: No conflict of interest to declare.
    Gas gangrene
    Clostridium perfringens
    The patient was transferred briefly to the intensive care unit, Spontaneous Gas Gangrene Due to Clostridiumand piperacillin and clindamycin were added to the therapy regiperfringens
    Gas gangrene
    Clostridium perfringens
    Clostridium Infections
    Clostridiales
    Gangrene
    Clostridium septicum
    Citations (11)
    Gas gangrene
    Clostridium perfringens
    Gangrene
    Citations (1)
    Clostridium Perfringens infection is an extremely fatal condition which is difficult to diagnose in first instance.A 65 year old lady para 3, presented with acute abdominal pain and vomiting to the surgical emergency.She was admitted,investigated and kept on conservative management.Her blood investigations, CT scan findings suggested bowel perforation.On laparotomy, acute gas gangrene infection of uterus was found leading to myometrial necrosis and perforation.Hysterectomy was performed and patient started on antibiotics but patient did not improve in postoperative period and expired.On histopathology, sepsis with gas gangrene was confirmed.Clostridium Perfringens infection affecting primarily uterus is a very rare so there is need to spread the awareness of this infection to prevent mortalities because of this infection.
    Clostridium perfringens
    Gas gangrene
    Perforation
    Clostridium septicum
    Gangrene
    A Clostridium perfringens-like strain was isolated from a case of gas gangrene. The morphological properties and the lecithinase reaction of the isolate were very similar to those of C. perfringens; however, the lecithinase reaction was only slightly suppressed by C. perfringens alpha-antitoxin serum and the organism was identified as Clostridium absonum from its biochemical properties.
    Lecithinase
    Clostridium perfringens
    Gas gangrene
    Antitoxin
    Citations (9)