1. The relative bactericidal activities of
penicillins F, G, K, and X against Type I pneumococcus in vitro were 60, 100, 180, and 135. The corresponding activities against Streptococcus pyogenes, strain C-203, were 75, 100, 115, and 145, respectively. 2. The total curative doses (CD(50)) of
penicillins F, G, K, and X in
pneumococcal infections of white mice (ten
injections at 3 hour intervals) were 4.6, 3.8, 20, and 2.4 mg. per kg., respectively, or relative activities of 83, 100, 19, and 160, referred to G as 100. 3. The corresponding curative doses in
streptococcal infections of white mice were 2.6, 1.3, 14.0, and 0.5 mg. per kg., or relative activities of 50, 100, 9, and 260. 4.
Penicillin K was therefore one-tenth as active in vivo as would be implied by its bactericidal activity in vitro. This probably reflects its rapid inactivation in vivo, evidenced by the low and evanescent blood levels observed in both rabbits and man, and the low urinary recovery of this species of
penicillin. 5.
Penicillin X was significantly more active therapeutically than its bactericidal activity in vitro would imply. This probably reflects its slower inactivation in vivo, evidenced by the somewhat higher and more prolonged blood levels afforded by this
penicillin in comparison with
penicillin G. Judged by the mouse
infections with the strains here used,
penicillin X is the
penicillin of choice in the treatment of
infections with pneumococcus Type I and hemolytic streptococci. 6. The curative dose of
penicillin in streptococcal and
pneumococcal infections paralleled the varying susceptibility of these organisms to
penicillin in vitro.