234 NATURE OF ANTIBIOTIC ACTION 



Entamoeba histolytica in 1 1400,000 dilution, and in cytolyzing T . equi- 

 ferdum in i :2,000 dilution (20). Extracts of cells of B. subtilis with 

 ether or chloroform in an acid medium (pH 2.5), redissolved in an 

 aqueous alkaline solution (^H 8.5), were found to be active against 

 staphylococci, E. coli, and M. tuberculosis (693). 



Penicillin 



In his first description of penicillin, Fleming recorded (261) that 

 "it was noticed that around a large colony of a contaminating mould the 

 staphylococcus colonies became transparent and were obviously under- 

 going lysis." Penicillin was referred to by Fleming as a bactericidal 

 agent and the conclusion was reached that it belonged to the group of 

 slow-acting antiseptics, since staphylococci were completely killed only 

 after an interval of 4^ hours, even in a concentration 30 to 40 times 

 that required for complete inhibition of the culture in broth. Florey 

 and Florey (275), however, concluded, as a result of in vitro experi- 

 ments, that penicillin is bacteriostatic and not bactericidal, at least in 

 concentrations suitable for chemotherapeutic purposes. This led Garrod 

 to state that "penicillin is in a true sense an antiseptic rather than a 

 germicide: it does not kill bacteria quickly." The action of penicillin 

 was found to be affected by changes in temperature, reaction of the sub- 

 strate, and age of the bacterial culture (320, 321 ). 



In addition to its marked bacteriostatic effect, penicillin has also been 

 found to be decidedly bactericidal j this is accelerated by an increase in 

 temperature from 4° to 42° C. but is impaired by an increase in acidity 

 of medium between f¥l 7.0 and 5.0. The rapid drop in the number of 

 bacteria within the first 15 minutes after application of the penicillin 

 was interpreted (594) as indicative of its bactericidal action in vivo. 

 Young cells are particularly susceptible, whereas mature cells are 

 neither lysed nor readily killed. The bacteriolytic action of penicillin 

 upon sensitive organisms is greatest at the maximum rate of multiplica- 

 tion (507, 512). The lysis of bacteria by penicillin depends upon their 

 ability to produce autolysin. Bacteria are resistant to the lysin when liv- 

 ing and become sensitive to it after the cells have been killed by penicil- 

 lin or by other agents. The rate of bacteriolysis is thus controlled by 

 bacterial multiplication and production of autolysin (913). 



