Arlyne D. Musselman

The bactericidal action of penicillin in vivo: the participation of the host, and the slow recovery of the surviving organisms.

Excerpt Although penicillin is known to be actively bactericidal, there is reason to believe that its therapeutic activity is not determined solely by that direct bactericidal action, and that othe...

The Low Therapeutic Activity of Penicillin K Relative to That of Penicillins F, G, and X, and Its Pharmacological Basis

One hour after the injection into rabbits or man of penicillins F, G, K, and X at 0.6 mg./kg., blood levels of K were one-fourth to one-eleventh of those observed with the other penicillins, and K persisted at demonstrable levels for relatively short periods. In both rabbits and man the recovery of K in the urine averaged 30-35 per cent. This compares with an average recovery for F, G, and X of 74 per cent in rabbits and 91 per cent in man. In the treatment of experimental pneumococcal infections in white mice, an impure preparation of K was one-sixth as active as G and one-eighth as active as X. In the treatment of experimental streptococcal infections in white mice, a pure preparation of K was one-eleventh as active as G, and one-thirtieth as active as X. The above data suggest that penicillin K is inactivated in the body to a greater extent and more rapidly than either F, G, or X, resulting in a far lower therapeutic activity than would be anticipated from its bactericidal action in vitro. It seems clear that the amount of K in commercial penicillin should be minimized; and it would seem desirable to standardize impure mixtures of penicillins for therapeutic use by some method other than their bactericidal activity in vitro.

THE BLOOD LEVELS AND RENAL CLEARANCE IN RABBITS AND MAN OF AN ANTIBIOTIC DERIVED FROM B. SUBTILIS (BACITRACIN)

The renal clearances of penicillins F, G, and X have been shown to approximate the total renal plasma flow (1, 2), varying between 529 and 865 ml. per minute in man, and 23 to 111 ml. per minute in rabbits (2). In consequence of that rapid excretion, the serum concentration of penicillin G decreases after its intramuscular injection in aqueous solution, at an average rate of 2 to 3 per cent of the residual penicillin per minute, and 70 to 80 per cent per hour; and it disappears from the blood even more rapidly after intravenous injection (3, 8). A therapeutic agent equal to penicillin in bactericidal activity, but with a slower rate of absorption or excretion, would provide effective levels for longer periods of time, and might be correspondingly more effective than penicillin similarly injected. The antibiotic agent discovered, by Johnson, Anker and Meleney (4) in culture filtrates of a strain of B. subtilis (Tracy), and termed by them bacitracin, possesses some of these properties. As will be here shown, it is excreted by both rabbits and man at a rate which corresponds approximately to the rate of glomerular filtration, rather than to the total renal plasma flow. In consequence, the blood levels observed after its intravenous or intramuscular injection fall off more slowly than do those of penicillin, and a given dosage provides effective levels for longer periods. The implications of these findings with respect to the therapeutic efficacy of this agent are discussed in the text.