Conclusions and SummaryThe bacteria (Staphylococcus pyogenes, Klebsiella pneumoniae, Escherichia coli, Streptococcus faecalis) multiply abundantly on the blood plasma of the guinea pig whose«natural»bactericidal activity has been neutralized by the polyancthol sulfonate of sodium (Iiquoid). The growth curves of these microorganisms are as regular in this medium as in an ordinary broth.The multiplication of the bacteria starts without lag phase if the plasma is inoculated with germs having reached the exponential phase of growth in an identical medium. The growth curves can be reproduced even when the plasma comes from a different guinea pig in each experiment.The polyanethol sodium sufonatc does not modify the antibacterial activity of the antibiotics which have been studied except for polymyxin li and colimycin.The kinetic studies, carried on in broth as well as in plasma, have brought out the following facts :The penicillins (penicillin G, mcthicillin, oxacillin and ampicillin) all act in the same manner on a Staphylococcus aureus which docs not produce penicillinase. The action curves show remarkable characteristics. The death rate of the Staphylococcus aureus is proportional to the rate of growth of the germ in a control culture; the two curves are symmetrical. The lethal action of the penicillins are noted only on bacteria in multiplication phase. The faster this multiplication the greater the death speed of the micro-organisms. The anabolic potential of the survivors of a population of bacteria dying under the action of penicillins remains unimpaired. The introduction of penicillinase into the medium shows it : germs multiply again without delay at the rhythm of the control culture. On the other hand, the death speed of the Staphylococcus annus is not proportional to the penicillin concentration in the medium. Beyond a concentration which is close to the minimum inhibitory concentration, the action reaches a limited speed. As shown by the graph, the slope of the curves docs not increase when the penicillin concentration rises above this conccntra-iton. As regards the penicillins with a strong proteic connection (oxacillin), their mode of action, apart from a loss of activity, is identical in plasmatic medium.If one studies the action of penicillin (penicillin G and ampicillin), no longer on a Staphylococcus aureus but on a E. coli the profile of the curves is strongly modified. These curves may be split into three segments :a) bacteriostatic segment, during which the bactericidal action does not manifest itself; the length of this segment is proportional to the antibiotic concentration; very long (several hours) at a low concentration, it disappears almost entirely at higher concentrations to make room, directly, for the second segment;b) the second segment is characterized in broth by a stiff slope, which indicates a very fast bactericidal action; in opposition to what was observed concerning the Staphylococcus aureus, this segment is not symmetrical to the growth curve of the control culture; nevertheless, the very stiff slope of this segment does not seem to increase by a rise of concentration; this concentration therefore only acts in shortening the«bacteriostatic»phase and in allowing the earlier installation of the fast bactericidal phase of action;c) the last segment of the curve shows a slow bactericidal action expressing the action of penicillin on the germs with a probably reduced metabolic activity.In the case of E. coli, the use of the plasmatic medium has been explained by a fairly marked slackening of the fast stage of the bactericidal action. The penicillins present in the plasma of treated animals have an action identical to that which is obtained by the introduction of these substances in vitro in the plasma.To understand the mode of action of streptomycin it is necessary to introduce a complementary parameter : the rapid fixation of this antibiotics on the surface of the germ. Removed from the medium containing streptomycin, the micro-organisms do not multiply immediately, the growth of the survivors is delayed; on solid medium the colonies slowly take form. The term«bactericidal»is illusive at certain concentrations. If these concentrations are sufficiently high, the curve of action in broth, unquestionably bactericidal, even after washing of the bacteria, shows three segments with characteristics similar to those described for the action of penicillin on a E. coli. The plasmatic medium reinforces the action of streptomycin, the bactericidal action is faster and the multiplication of the survivors is postponed for many hours. After in vivo passage, by injection to the animal, the mode of action of streptomycin is identical to the one observed in plasmatic medium.The curves of action of kanamycin are very similar to the streptomycin curves.The bactericidal activity determined by tctracyclin in sufficiently concentrated broth does not exist in plasmatic medium. Nevertheless, the bacteriostatic activity is strictly maintained in the plasma. The plasma of treated animals is endowed with an activity solely bacteriostatic.Chloramphenicol, bactericidal or bacteriostatic in broth, suffers, according to the concentrations, an appreciable loss of activity in plasmatic medium. The plasma of guinea pigs, treated by chloramphenicol (succinate) injection is onlv endowed with a negligible antibacterial activity.The bactericidal activity of erythromycin is present but slow in plasma and in broth. To appreciate the antibacterial activity of erythromycin, it is necessary to lenghten the time of contact with the bacteria.Within the limits of the experiments presented, this study attempts to contribute to the understanding of the mode of action of the antibiotics at the site of infection, of which the plasma is an important constituent part.