258 NATURE OF ANTIBIOTIC ACTION 



aspergillic acid, slight resistance to gliotoxin, and marked resistance to 

 penicillin, streptomycin, and pyocyaninj resistance was attained more 

 rapidly and was lost more slowly for streptomycin. An increase in re- 

 sistance to one did not affect the sensitivity to other antibiotics (510a). 



The resistance of staphylococci to penicillin, or penicillin-fastness, 

 was found to be reversible j strains were shown to change frequently to 

 the sensitive state when they were cultured in antibiotic-free media. It 

 has even been suggested that the reversion may be more rapid in vivo 

 than in vitro (914). Strains of staphylococci possessing increasing re- 

 sistance to penicillin were isolated from infections treated with this sub- 

 stance (756). 



In a study of 1 15 strains of staphylococci, 13.9 per cent proved to be 

 resistant to penicillin j the resistant strains produced penicillinase, but 

 not the susceptible ones (72). Of 128 strains collected from various 

 sources before the advent of penicillin treatment, 123 were inhibited 

 by one-eighth unit or less of penicillin per ml., 2 were inhibited by one- 

 fourth unit, and 3 by half a unit. The 5 strains showing slightly in- 

 creased resistance were nonpathogenic. Thirty-one strains from hospital 

 wards in which penicillin had been used extensively, particularly in 

 local application to wounds, were found to be largely penicillin resist- 

 ant. These strains showed no cultural differences from normal strains. 

 Whether they developed from sensitive parent organisms in the same 

 wound or were the result of cross infection, either from carriers or air 

 borne, was not determined (682). When staphylococci were made re- 

 sistant to penicillin by cultivation in penicillin-containing medium, this 

 acquired resistance or "fastness" was lost when the cultures were grown 

 in plain medium. Pneumococci, however, acquired resistance less 

 readily and maintained it even when subcultured in plain media (914). 

 Patients treated with penicillin gave a much larger proportion of re- 

 sistant strains of S. aureus than patients not so treated (725). 



Bacterial cells that have become adapted to resist the action of a par- 

 ticular antibiotic substance are not resistant to the action of others. How- 

 ever, bacteria "trained" to resist one substance may also acquire resist- 

 ance to another by a process of adaptation. This was brought out by 

 Davies et al. (170) in studies on sulfonamides and proflavine. Adapta- 

 tion of bacteria to an antibacterial agent has been explained as follows: 



