The Effect of Impurities on the Chemotherapeutic Action of Crystalline Penicillin

Abstract

Mouse-protection studies have been carried out on a series of over 25,000 mice. The results indicate that impure penicillin is 3-5 times more effective than crystalline penicillin G in protecting animals against experimentally produced hemolytic streptococcal infections in mice. The presence of a substance responsible for such enhanced activity is not correlated with the potency in U. per mg or with the Bacillus subtilis / Staphylo-coccus aureus differential ratio. Likewise it is not correlated with the amt. of phenylacetic acid present. There is no evidence that it is associated with the degradation products of penicillin. As in the case of hemolytic streptococcal infections, impure penicillin is more effective than crystalline penicillin G in protecting animals against experimentally produced pneumococcal infections in mice. On a unitage basis (CD50) the relative chemotherapeutic efficacy of penicillins X, dihydro-F, F, G, and K against this infection, under the exptl. conditions used, was on the order of 302, 180, 116, 100, and 63, respectively; on a gravimetric basis, 194, 180, 107, 100, and 88, respectively. The factor in impure penicillin which enhances the chemotherapeutic activity of crystalline penicillin G is present in the original penicillin fermentation liquor and may be demonstrated during the extraction of penicillin in those fractions in which penicillin G is recovered. The chemotherapeutic activity of crystalline penicillin G may be enhanced by dissimilar substances not specific for impure penicillin. Furthermore, crystalline penicillin K may enhance the activity of crystalline penicillin G. The effect of penicillin G plus K is greater than would be anticipated from the total number of units present. The chemotherapeutic activity of penicillins X, dihydro-F, and at times K, may also be enhanced by penicillin impurities.-G. L. Hobby.