Effect of Penicillin Dosage Schedule on Treatment of Experimental Typhoid Infections in Mice

Abstract

Summary and conclusions

When mice were infected with a relatively penicillin-resistant Salmonella typhosa, it was found that the penicillin PD₅₀ varied with the treatment schedule. A smaller total amount of penicillin was required for protection when the treatment was given as a single injection than when 2, 3, 6, or 12 doses were divided equally within a 24-hour period. When the time interval between 2 doses was varied from 2 to 36 hours, it was found that the PD₅₀ for the 2 dose 2-hour schedule represented an even smaller total amount, and, therefore, a more economical use of penicillin than did the single injection schedule.

These data would suggest that in the treatment of infections caused by organisms of high penicillin resistance, the common practice of dividing the total daily amount of penicillin into frequently injected doses may be an inefficient means of therapy. It would appear that the total amount of penicillin to be used in one day would be more effective if given as a few large doses. This procedure would result in the higher plasma penicillin concentrations and the correspondingly increased tissue concentrations required for a bacteriocidal action against relatively resistant organisms.