title: Group A streptococcal bacteremia: the role of tumor necrosis factor in shock and organ failure.
abstract: Severe group A streptococcal infections associated with early onset shock and multiorgan failure define the streptococcal toxic shock syndrome. In the United States, group A streptococcal strains most commonly isolated are M types 1 and 3, which produce pyrogenic exotoxin type A. The role of tumor necrosis factor (TNF)-alpha and the dynamics of cardiovascular and laboratory abnormalities were investigated in a baboon model of group A Streptococcal bacteremia that mimics human Streptococcal toxic shock syndrome. Profound hypotension, leukopenia, metabolic acidosis, renal impairment, thrombocytopenia, and disseminated coagulopathy developed within 3 h after intravenous infusion of M type 3, pyrogenic exotoxin A-producing group A streptococci. Serum TNF-alpha peaked at 3 h and returned to baseline by 10 h. Mortality was 100%. Anti-TNF-alpha monoclonal antibody treatment markedly improved mean arterial blood pressure, tissue perfusion, and survival, suggesting that TNF-alpha plays an important role in the induction of shock and organ failure in group A streptococcal bacteremia.
authors.affiliation: Infectious Diseases Section, VA Medical Center, Boise, Idaho 83702, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Stevens
authors.forename: A E
authors.initials: AE
authors.lastname: Bryant
authors.forename: S P
authors.initials: SP
authors.lastname: Hackett
authors.forename: A
authors.initials: A
authors.lastname: Chang
authors.forename: G
authors.initials: G
authors.lastname: Peer
authors.forename: S
authors.initials: S
authors.lastname: Kosanke
authors.forename: T
authors.initials: T
authors.lastname: Emerson
authors.forename: L
authors.initials: L
authors.lastname: Hinshaw
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D016470:Bacteremia / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D010215:Papio; D012772:Shock, Septic / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D013290:Streptococcal Infections / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D013297:Streptococcus pyogenes / Q000145:classification / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha