270 DISEASE CONTROL 



The bacteriostatic power of penicillin against streptococci and staphylo- 

 cocci is not inhibited to any extent by protein breakdown products or 

 by pus, which neutralize the bacteriostatic action of sulfonamide 

 drugs. The leucocytes remain active in any concentration of peni- 

 cillin usually employed in intravenous injection. 



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

 tion of sulfonamides. It is effective in the treatment of hemolytic 

 streptococcus, pneumococcus, and gonococcus infections, which are 

 resistant to sulfonamides. It has not been found effective, however, 

 in the treatment of subacute bacterial endocarditis (782). 



On repeated passage through broth containing penicillin, pneumo- 

 coccus cultures as well as Sta-phylococcus sp. and S. fyogenes (604) 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 (840). 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. This increase in resistance may be one of the dangers of using 

 "homemade" penicillin. 



Survival of a certain number of cells of staphylococci in a culture 

 treated with penicillin may be due to the fact that these cells are tem- 

 porarily in a nondividing state, since the antibiotic kills the bacteria that 

 are about to divide. Such cells were designated "persisters" (57) } their 

 descendants are easily killed by the antibiotic. This concept led to the 

 recommendation of intermittent treatment by penicillin: treatment to 

 be interrupted to permit the bacteria to multiply and thus become again 

 vulnerable. This concept has not been universally accepted (321), some 

 investigators actually warning against too early interruption of peni- 



