Three strains of pneumococcus (types I and III), equally sensitive to
penicillin, have been shown to be killed by the
antibiotic in vitro when grown either in enriched beef infusion broth or in a thin serous exudate. Killing of the bacteria resulted promptly when the
penicillin was added during the logarithmic phase of growth but failed to occur if addition of the
antibiotic was delayed until the later "stationary" growth phase. In analogous experiments with thick purulent exudates from established subcutaneous
abscesses, the pneumococci failed to grow rapidly, and added
penicillin exerted only a relatively slow bactericidal effect. The relevance of these in vitro observations to the curative action of
penicillin was demonstrated in a systematic histologic study of the antimicrobial effect of the
drug in experimental (type I)
pneumococcal pneumonia. Evidence was obtained that at least two distinct processes are involved. The first, the direct bactericidal effect of the
penicillin itself, was shown to operate in the outer
edema zone of the spreading pneumonic lesion where the micro-organisms multiply rapidly in the thin serous exudate. The second, which predominates in the older more central portions of the lesion, was demonstrated to depend upon destruction of the pneumococci by phagocytosis. Here the bacteria, having presumably reached a relatively stationary phase of growth in the alveolar exudate, are resistant to the bactericidal action of the
penicillin but are readily destroyed by the phagocytes.