GROUP-A STREPTOCOCCAL BACTEREMIA - THE ROLE OF TUMOR-NECROSIS-FACTOR IN SHOCK AND ORGAN FAILURE

Severe group A streptococcal infections associated with early onset of shock and multiorgan failure define the streptococcal toxic shock syn drome. In the United States, group A streptococcal strains most common ly 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 bab oon model of group A streptococcal bacteremia that mimics human strept ococcal toxic shock syndrome. Profound hypotension, leukopenia, metabo lic acidosis, renal impairment, thrombocytopenia, and disseminated coa gulopathy 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%. An ti-TNF-alpha monoclonal antibody treatment markedly improved mean arte rial blood pressure, tissue perfusion, and survival, suggesting that T NF-alpha plays an important role in the induction of shock and organ f ailure in group A streptococcal bacteremia.