1. A large proportion of cultures of coagulase-positive Staphylococcus aureus are susceptible to penicillin. Some strains of definitely high natural resistance may be encountered.

  2. Staphylococci may be made resistant to penicillin by growth in progressively increasing concentrations in broth. Their metabolic activity is retarded, and their pathogenicity is reduced or lost. The coagulase reaction is unaffected. This in vitro resistance is temporary; restoration to sensitivity, but only partial return to pathogenicity, may be effected by serial transfer in broth.

  3. Staphylococci may acquire resistance during penicillin therapy. Their metabolic activity is retarded, but their pathogenicity is often unaltered. The coagulase reaction is unaffected. This resistance appears to be permanent.

  4. Penicillin has no effect on the coagulase reaction. It occurs even in the presence of concentrations of penicillin which are ultimately bactericidal.

  5. Penicillin has no effect on the formation of staphylococcal alpha-toxin, and neither enhances or destroys pre-formed toxin.

  6. The implication of resistance acquired by staphylococci during penicillin therapy is discussed.

1

The work described in this paper was done under a contract recommended by the Committee on Medical Research between the Office of Scientific Research and Development and the Hospital for Joint Diseases. The penicillin was provided by the Office of Scientific Research and Development from supplies assigned by the Committee on Medical Research for clinical investigations recommended by the Committee on Chemotherapeutic and Other Agents of the National Research Council.

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