STUDIES ON THE PATHOGENESIS OF STAPHYLOCOCCAL INFECTION : III. THE EFFECT OF TISSUE NECROSIS AND ANTITOXIC IMMUNITY.

Necrosis of rabbit skin produced by thermal injury was found to result in a striking increase in local infectivity of staphylococci that were coagulase-positive and hemolytic, but no local increase in the infectivity of non-pathogenic staphylococci. Infection produced in necrotic burns extended beyond the area of burn and was characterized by hemorrhage, edema, and necrosis of contiguous normal skin. Such infections, however, never resulted in bacteriemia or metastatic abscesses, and there was no effect of the necrotic burn upon the infectivity of staphylococci injected into normal skin of the burned animal. Recovery of rabbits from severe burn infections was associated with the development of high titers of serum antibody to the alpha hemolysin or dermonecrotoxin of the staphylococcus. Thirty to 100 days after the initial burn infection, it was found that rabbits could no longer be infected in a necrotic burn, although infection induced in normal skin of these resistant animals was no different from that in normal rabbits. Immunity to infection by pathogenic staphylococci in necrotic burns could be induced by vaccination with potent alpha hemolysin toxoid, and this immunity was passively transferable with rabbit antiserum. No strain specificity was detected for this immunity in that immunization with toxoid prepared from bacteriophage type 52/42B/80/81 staphylococci protected animals against infection in a necrotic burn by other typable and non-typable staphylococci. Histopathological study of infected necrotic burns in normal rabbits showed extensive necrosis, hemorrhage, edema, and many masses of bacteria but leucocytic infiltration was observed only at the margin of the infection. In contrast, the infected necrotic burns in animals immunized with alpha hemolysin toxoid showed few bacteria and marked leucocytic infiltration throughout the burn. These experiments have, therefore, demonstrated a significant immunity to infection by pathogenic staphylococci in necrotic tissue but not in normal skin, associated with serum antibody to the alpha hemolysin or dermonecrotoxin of the bacteria. The implications of these findings are discussed.