ANTIBACTERIAL ACTION 23 5 



Penicillin is markedly sporicidal against sensitive organisms j this 

 action is greater in milk than in water, especially if preceded by sub- 

 lethal heating of the spores (162). Penicillin is active against spiro- 

 chetes (399), including Treponema fallidum (225, 296). 



Penicillin is thus found to be actively bactericidal in a medium and 

 an environment in which active multiplication of the bacteria occurs, 

 since it acts best in good culture media such as broth or serum and poorly 

 in water or saline solutions. Although penicillin kills large numbers of 

 sensitive bacteria, it does not always kill all the bacteria present, but 

 leaves a few cells that are resistant to its action. These soon begin to 

 multiply, giving rise to a resistant culture. 



Penicillin affects a metabolic function of the bacteria during the early 

 stages of their development. Certain antibacterial substances, like hel- 

 volic acid, neutralize the effect of penicillin on the bacteria, whereas 

 others, like sulfanilamide, have a synergistic effect. The latter is espe- 

 cially well marked with strains of staphylococci that are naturally re- 

 sistant to penicillin (121). 



Although penicillin is active primarily on gram-positive bacteria, it 

 also has an effect on certain gram-negative bacteria, but not on the colon 

 organism. Hemophilus, or Brucella. The gram-negative cocci can be 

 divided into two groups, on the basis of their sensitivity to penicillin : 

 N. gonorrhoeae, N. intracellular, and A^. catarrhalis, which are sensi- 

 tive j and A^. -flava and other nonpathogenic Neisseriae, which are not 

 sensitive. 



Some species of Hemophilus, such as H. ducreyi, are as sensitive to 

 penicillin as is S. aureus, although less so than S. hemolyticus (659). 

 High potency preparations of penicillin were found (431) to have an 

 inhibitive effect even on E. coli. The susceptibility of gram-negative 

 bacteria to penicillin is much greater in synthetic than in complex or- 

 ganic media; in the case of the latter, various polypeptides and pos- 

 sibly some amino acids appear to neutralize the effect of penicillin upon 

 E. coli, the antagonism being partly removed by methionine (852). In 

 studies on the effect of penicillin on bacteria in urine, it was shown 

 (402) that 90 times the dose required to eliminate S. aureus will affect 

 S. faecalis, 240-fold increase will act on P. vulgaris, and 900-fold will 

 act on £. coli (880). Although Salmonella strains were inhibited by 



