- Dennis L Stevens, MD, PhD
Dennis L Stevens, MD, PhD
- Professor of Medicine
- University of Washington School of Medicine
- Amy Bryant, PhD
Amy Bryant, PhD
- Associate Professor, Department of Medicine
- University of Washington
Clostridial myonecrosis (gas gangrene) is a life-threatening muscle infection that develops either contiguously from an area of trauma or hematogenously from the gastrointestinal tract with muscle seeding. Early recognition and aggressive treatment are essential.
There are two major presentations of clostridial gas gangrene: traumatic and spontaneous. Traumatic gas gangrene is most commonly caused by Clostridium perfringens; spontaneous gangrene is most commonly caused by Clostridium septicum.
Issues related to necrotizing muscle infections due to Clostridium species will be reviewed here. Issues related to streptococcal necrotizing myositis and infections involving the skin and fascia are discussed separately. (See "Necrotizing soft tissue infections".)
SPECTRUM OF CLOSTRIDIAL INFECTIONS
Clostridium species are widespread in nature due to their ability to form endospores. They are commonly found in soil and marine sediments as well as human and animal intestinal tracts. Categories of clostridial soft tissue infections include wound contamination, anaerobic cellulitis, myonecrosis (gas gangrene), and necrotizing fasciitis .
●Wound contamination with soil containing clostridial spores or vegetative organisms may occur, although contamination with clostridial species in the absence of devitalized tissue does not necessarily lead to infection. In one study, for example, 30 to 80 percent of open traumatic wounds were contaminated with clostridial species .
- Awad MM, Bryant AE, Stevens DL, Rood JI. Virulence studies on chromosomal alpha-toxin and theta-toxin mutants constructed by allelic exchange provide genetic evidence for the essential role of alpha-toxin in Clostridium perfringens-mediated gas gangrene. Mol Microbiol 1995; 15:191.
- MACLENNAN JD. The histotoxic clostridial infections of man. Bacteriol Rev 1962; 26:177.
- Wang Y, Lu B, Hao P, et al. Comprehensive treatment for gas gangrene of the limbs in earthquakes. Chin Med J (Engl) 2013; 126:3833.
- Centers for Disease Control and Prevention (CDC). Update: Clostridium novyi and unexplained illness among injecting-drug users--Scotland, Ireland, and England, April-June 2000. MMWR Morb Mortal Wkly Rep 2000; 49:543.
- Stevens DL, Laposky LL, McDonald P, Harris I. Spontaneous gas gangrene at a site of remote injury--localization due to circulating antitoxin. West J Med 1988; 148:204.
- McNee JW, Dunn JS. THE METHOD OF SPREAD OF GAS GANGRENE INTO LIVING MUSCLE. Br Med J 1917; 1:726.4.
- Robb-Smith AHT. Tissues changes induced by C. welchii type a filtrates. Lancet 1945; 2:362.
- Williamson ED, Titball RW. A genetically engineered vaccine against the alpha-toxin of Clostridium perfringens protects mice against experimental gas gangrene. Vaccine 1993; 11:1253.
- Stevens DL, Titball RW, Jepson M, et al. Immunization with the C-Domain of alpha -Toxin prevents lethal infection, localizes tissue injury, and promotes host response to challenge with Clostridium perfringens. J Infect Dis 2004; 190:767.
- Alouf JE, Geoffroy C. The Family of the Antigenically-Related, Cholesterol-Binding ("Sulphydryl-Activated") Cytolytic Toxins. In: Sourcebook of Bacterial Protein Toxins, Alouf JE, Freer JH (Eds), Academic Press, New York 1991. p.147.
- Bryant AE, Bergstrom R, Zimmerman GA, et al. Clostridium perfringens invasiveness is enhanced by effects of theta toxin upon PMNL structure and function: the roles of leukocytotoxicity and expression of CD11/CD18 adherence glycoprotein. FEMS Immunol Med Microbiol 1993; 7:321.
- Bryant AE, Stevens DL. Phospholipase C and perfringolysin O from Clostridium perfringens upregulate endothelial cell-leukocyte adherence molecule 1 and intercellular leukocyte adherence molecule 1 expression and induce interleukin-8 synthesis in cultured human umbilical vein endothelial cells. Infect Immun 1996; 64:358.
- Stevens DL, Tweten RK, Awad MM, et al. Clostridial gas gangrene: evidence that alpha and theta toxins differentially modulate the immune response and induce acute tissue necrosis. J Infect Dis 1997; 176:189.
- Bryant AE, Chen RY, Nagata Y, et al. Clostridial gas gangrene. I. Cellular and molecular mechanisms of microvascular dysfunction induced by exotoxins of Clostridium perfringens. J Infect Dis 2000; 182:799.
- Bryant AE, Chen RY, Nagata Y, et al. Clostridial gas gangrene. II. Phospholipase C-induced activation of platelet gpIIbIIIa mediates vascular occlusion and myonecrosis in Clostridium perfringens gas gangrene. J Infect Dis 2000; 182:808.
- Stevens DL, Troyer BE, Merrick DT, et al. Lethal effects and cardiovascular effects of purified alpha- and theta-toxins from Clostridium perfringens. J Infect Dis 1988; 157:272.
- Asmuth DM, Olson RD, Hackett SP, et al. Effects of Clostridium perfringens recombinant and crude phospholipase C and theta-toxin on rabbit hemodynamic parameters. J Infect Dis 1995; 172:1317.
- Whatley RE, Nelson P, Zimmerman GA, et al. The regulation of platelet-activating factor production in endothelial cells. The role of calcium and protein kinase C. J Biol Chem 1989; 264:6325.
- Weinstein L, Barza MA. Gas gangrene. N Engl J Med 1973; 289:1129.
- Hart GB, Lamb RC, Strauss MB. Gas gangrene. J Trauma 1983; 23:991.
- Terebelo HR, McCue RL, Lenneville MS. Implication of plasma free hemoglobin in massive clostridial hemolysis. JAMA 1982; 248:2028.
- Hübl W, Mostbeck B, Hartleb H, et al. Investigation of the pathogenesis of massive hemolysis in a case of Clostridium perfringens septicemia. Ann Hematol 1993; 67:145.
- Gorbach SL, Thadepalli H. Isolation of Clostridium in human infections: evaluation of 114 cases. J Infect Dis 1975; 131 Suppl:S81.
- Brook I. Anaerobic bacterial bacteremia: 12-year experience in two military hospitals. J Infect Dis 1989; 160:1071.
- Gozal D, Ziser A, Shupak A, et al. Necrotizing fasciitis. Arch Surg 1986; 121:233.
- Butler HM. Pathogenicity of washed C. welchii and mode of development C. welchii infections in man. Med J Aust 1943; 2:224.
- Keppie J, Robertson M. The in vitro toxigenicity and other characters of strains of C. welchii type A from various sources. J Pathol Bacteriol 1944; 56:123.
- Stevens DL. Clostridial infections. In: Stevens DL, Mandell GL, Atlas of Infectious Diseases (Ed), Churchill Livingstone, Philadelphia 1995. p.13.1.
- Gorbach SL. Clostridium perfringens and other clostridia. In: Infectious Diseases, Gorbach SL, Bartlett JG, Blacklow NR (Eds), WB Saunders, Philadelphia 1992. p.1587.
- Lorber B. Gas gangrene and other Clostridium-associated diseases. In: Principles and Practice of Infectious Diseases, 6th ed, Mandell GL, Bennett JE, Dolin R (Eds), Churchill Livingstone, Philadelphia 2005. p.2828.
- Darke SG, King AM, Slack WK. Gas gangrene and related infection: classification, clinical features and aetiology, management and mortality. A report of 88 cases. Br J Surg 1977; 64:104.
- Dylewski J, Wiesenfeld H, Latour A. Postpartum uterine infection with Clostridium perfringens. Rev Infect Dis 1989; 11:470.
- Altemeier WA, Fullen WD. Prevention and treatment of gas gangrene. JAMA 1971; 217:806.
- Stevens DL, Laine BM, Mitten JE. Comparison of single and combination antimicrobial agents for prevention of experimental gas gangrene caused by Clostridium perfringens. Antimicrob Agents Chemother 1987; 31:312.
- Stevens DL, Maier KA, Laine BM, Mitten JE. Comparison of clindamycin, rifampin, tetracycline, metronidazole, and penicillin for efficacy in prevention of experimental gas gangrene due to Clostridium perfringens. J Infect Dis 1987; 155:220.
- Stevens DL, Maier KA, Mitten JE. Effect of antibiotics on toxin production and viability of Clostridium perfringens. Antimicrob Agents Chemother 1987; 31:213.
- Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014; 59:e10.
- Kaide CG, Khandelwal S. Hyperbaric oxygen: applications in infectious disease. Emerg Med Clin North Am 2008; 26:571.
- Stevens DL, Bryant AE, Adams K, Mader JT. Evaluation of therapy with hyperbaric oxygen for experimental infection with Clostridium perfringens. Clin Infect Dis 1993; 17:231.
- Kainer MA, Linden JV, Whaley DN, et al. Clostridium infections associated with musculoskeletal-tissue allografts. N Engl J Med 2004; 350:2564.
- Ballard J, Bryant A, Stevens D, Tweten RK. Purification and characterization of the lethal toxin (alpha-toxin) of Clostridium septicum. Infect Immun 1992; 60:784.
- Stevens DL, Musher DM, Watson DA, et al. Spontaneous, nontraumatic gangrene due to Clostridium septicum. Rev Infect Dis 1990; 12:286.
- Johnson S, Driks MR, Tweten RK, et al. Clinical courses of seven survivors of Clostridium septicum infection and their immunologic responses to alpha toxin. Clin Infect Dis 1994; 19:761.
- Alpern RJ, Dowell VR Jr. Clostridium septicum infections and malignancy. JAMA 1969; 209:385.
- Yoder EL, Mendez J, Khatib R. Spontaneous gangrenous myositis induced by Streptococcus pyogenes: case report and review of the literature. Rev Infect Dis 1987; 9:382.
- Arteta-Bulos R, Karim SM. Images in clinical medicine. Nontraumatic Clostridium septicum myonecrosis. N Engl J Med 2004; 351:e15.
- Nordkild P, Crone P. Spontaneous clostridial myonecrosis. A collective review and report of a case. Ann Chir Gynaecol 1986; 75:274.
- Bodey GP, Rodriguez S, Fainstein V, Elting LS. Clostridial bacteremia in cancer patients. A 12-year experience. Cancer 1991; 67:1928.
- SPECTRUM OF CLOSTRIDIAL INFECTIONS
- CLOSTRIDIAL MYONECROSIS
- Traumatic gas gangrene
- - Pathogenesis
- - Clinical manifestations
- - Diagnosis
- - Treatment
- - Prognosis
- Spontaneous gas gangrene
- - Pathogenesis
- - Clinical manifestations
- - Diagnosis
- - Treatment
- - Prognosis
- DIFFERENTIAL DIAGNOSIS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS