ANTIBACTERIAL ACTION 229 



growth inhibiting and can, therefore, be designated as "bacteriostatics." 

 The bacteriostatics may be expected to be relatively nontoxic to animal 

 cells. Antibiotics of this class have possibilities as chemotherapeutic 

 agents for general administration and for the treatment of systemic in- 

 fections. 



In order to determine whether an antibacterial substance has chemo- 

 therapeutic potentialities, the effect of the antibiotic on bacterial respira- 

 tion can be determined by using the Barcro ft- Warburg apparatus. 

 If respiration is stopped by addition of the antibiotic in dilution of 

 1 : 1,000, the organisms may be said to have been killed, the substance 

 being an antiseptic which will be toxic to animal tissues. If, however, 

 the antibiotic produces little or no effect on respiration of the bacteria, 

 there is a probability that the substance has chemotherapeutic possi- 

 bilities. 



Chain and Florey further suggested that observations be made on: 

 (a) the toxicity of the antibacterial substance to leucocytes, a wide gap 

 between a toxic concentration and a bacteriostatic effect suggesting that 

 the substance may be useful, at least for local application j (b) the effect 

 of blood, pus, and tissue extracts on the bacteriostatic activity, inhibition 

 of activity being due to chemical combination between the active sub- 

 stance and a tissue constituent or to an inhibitory mechanism similar to 

 that of /)-amino-benzoic acid for the sulfonamides; (c) the toxicity of 

 the substance to mice when injected intravenously. Any therapeutically 

 active substance will be excreted unchanged or little changed in the 

 urine, since it does not combine with the tissue cells. 



Although Dubos (206) believed that none of the in vitro metabolic 

 screening methods at present available is satisfactory in a search for 

 new chemotherapeutic agents, Chain and Florey emphasized that those 

 antibiotics which pass the above biological tests can be expected to be 

 effective as general chemotherapeutic agents and to be worth further 

 investigation with mouse protection tests. 



Tyrothricin 



The phenomenon of antibiotic action by a specific substance can best 

 be illustrated by the action of tyrothricin upon bacterial cells. Five dis- 

 tinct stages have been described (201 ) : 



