In the early 1940s following the introduction of benzylpenicillin into clinical practice virtually all clinical isolates of S. aureus could be inhibited by fractions of a µg of the drug. By 1946 to 1949 the fraction of clinical isolates still sensitive to low concentrations of penicillin has dropped to 10% and inhibition of most S. aureus strains required several hundred µgs of benzylpenicillin, thus eliminating this antibiotic as an agent for the chemotherapy of S. aureus infections. The elimination of penicillin from the antibacterial armamentarium was caused by an enzyme, penicillinase, plasmid-born copies of which have quickly spread through the entire species of S. aureus. The origin of the penicillinase plasmid has remained unknown.
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