228 DISEASE CONTROL 



Penicillin is active against strains of bacteria that are resistant to the ac- 

 tion of sulfonamides (273, 566, 881). It is effective in the treat- 

 ment of hemolytic streptococcus, pneumococcus, and gonococcus in- 

 fections, which are resistant to sulfonamides. It has not been found 

 effective, however, in the treatment of subacute bacterial endocar- 

 ditis (748). 



On repeated passage through broth containing penicillin, pneumo- 

 coccus cultures as well as Stafhylo coccus sp. and 5. -pyogenes (564) in- 

 creased in resistance to penicillin. This was accompanied by a propor- 

 tional loss of virulence. Small colony variants (G forms) of S. albus 

 showed a specially high resistance to penicillin (806). Two strains of 

 pneumococcus developed resistance to penicillin as a result of serial 

 passage through mice treated with it. The degrees of resistance devel- 

 oped and acquired varied significantly with the strains. In the case of one 

 strain, resistance was not impaired by 30 serial passages through nor- 

 mal mice. The development of resistance in vivo was accompanied by 

 an increase in resistance to penicillin in vitro. The response of the pneu- 

 mococci to sulfonamides was not altered by the development of resist- 

 ance to penicillin. The mechanisms whereby staphylococci become re- 

 sistant to sulfonamides and to penicillin appear to be distinctly differ- 

 ent (846, 847). 



Toxicity. As to the toxicity of penicillin, it was found (7) that mice 

 were little affected by the intravenous injection of 10 mg. of penicillin j 

 they became ill from the use of 20 mg. but recovered shortly. One hun- 

 dred milligrams of crude penicillin given intravenously to man caused 

 a shivering attack with a rise of temperature in about an hour. The lat- 

 ter was due to the presence of a pyrogenic substance in the preparation. 

 Certain isolated fractions of penicillin had no such pyrogenic effect. 

 Penicillin was toxic to mice when given intravenously in single doses 

 of 0.5, i.O, 1.5, and 2.0 gm. per kilogram. More highly purified prepa- 

 rations were less toxic. Higher concentrations were required for lethal 

 effect from subcutaneous administration. The toxic dose is 64 times 

 greater than the effective dose (753). 



The relative toxicity of various salts of penicillin was found (967) to 

 be, in increasing order, Na, NH4, Sr, Ca, Mg, and K. Based on milli- 

 grams of the cation at the LD-,o dose of salts of penicillin, the relative 



