PENICILLIN-RESISTANT STAPHYLOCOCCI: MECHANISMS INVOLVED IN THE DEVELOPMENT OF RESISTANCE.

While staphylococci are among the species of gram-positive bacteria considered to be susceptible to the antibacterial action of penicillin, a number of investigators have reported that there are some strains of coagulase-positive staphylococci which are naturally resistant to penicillin (1 to 11). Of added clinical importance is the fact that pathogenic strains originally sensitive to therapeutic concentrations of penicillin may become resistant to the antibiotic in patients who have received treatment with penicillin (7, 12 to 19). In an attempt to define the nature of the resistance of staphylococci to penicillin, the results of several studies have appeared in which sensitive strains have acquired a high degree of resistance by in vitro methods (4, 11, 13, 18, 20 to 24). Todd and Turner (25) succeeded in adapting 2 strains of staphylococcus resistant to penicillin by making repeated subcultures of the cocci in increasing quantities of penicillin. When the strains had acquired resistance, they subcultured the organisms daily in broth without penicillin and observed that there was a rapid decline in resistance. As a result of these observations, they assumed that the resistance of staphylococci which developed in the body was not a permanent characteristic of the organisms and that, upon withdrawal of the drug, the bacteria would quickly revert to a state of sensitivity. On the other hand, Spink and Ferris (26) showed independently that staphylococci which had acquired resistance in vitro lost this resistance when grown and transferred in the absence of penicillin, but that penicillin-resistance attained in the body appeared to be a permanent characteristic of the bacteria. This distinction between acquired in vitro and in vivo resistance has been confirmed by others (11, 18). One of the major problems related to penicillinresistance is whether penicillinase plays a role in