PEDIATRICS Vol. 5 No. 1 January 1950, pp. 78-89
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EXPERIMENTAL BASIS FOR PREDICTION OF THERAPEUTIC EFFICACY OF STREPTOMYCIN IN INFECTIONS CAUSED BY GRAM NEGATIVE BACILLI

HATTIE E. ALEXANDER M.D.1, GRACE LEIDY A.B.1, WINIFRED REDMAN A.B.1, and EROS SIMAKOW A.B.1

1 The Babies Hospital and the Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, N.Y.

Cells with varying degrees of resistance to streptomycin, 25, 100 and 1000 µg./cc., have been demonstrated in large populations of eight species of gram negative bacilli prior to exposure to streptomycin. These resistant variants exhibit traits characteristic of bacterial mutants and therefore arise spontaneously, independent of the action of streptomycin.

The known differences in therapeutic efficacy of streptomycin among infections caused by these eight species have been demonstrated to be closely correlated with two factors.

1 . In infections in which streptomycin has been proven of therapeutic value—H. influenzae, H. pertussis and E. coli—the rate of occurrence of new mutants resistant to 25 and 100 µg./cc. is so low that they cannot be expected to play a significant role in emergence of resistance during streptomycin therapy.

In cultures of organisms causing infections in which streptomycin has been unsuccessful therapeutically—Salmonella, S. typhosa and Ps. aeruginosa—the rate of occurrence of mutants resistant to 25 and 100 µg./cc. is relatively high; these mutants doubtless play an important role in emergence of resistance to streptomycin and therapeutic failure.

2. Streptomycin in a concentration of 10 µg./cc. is primarily bactericidal against the species which cause infections in which streptomycin therapy has been of value. This concentration is not primarily bactericidal against those organisms causing infections in which streptomycin has failed therapeutically.

These data suggest that knowledge of these two factors in vitro can offer a reliable basis for predicting the therapeutic efficacy of streptomycin in a given infection. For example, in Shigella and H. parapertussis infections, in which streptomycin has not been clinically evaluated, one can predict success in the former and failure in the latter.

Submitted on March 17, 1949