The Antibacterial Action of Erythromycin.

The results of studies on some properties of erythromycin which may be important in its clinical and laboratory applications have been reported. 1. Erythromycin solutions retained their activity after prolonged storage in the cold or in the frozen state but showed progressive deterioration after several days at room or incubator temperatures or after brief exposures to 60°C or higher. 2. Filtration of erythromycin through bacterial filters entailed the loss of some activity. 3. The antibacterial action of erythromycin increased progressively with increasing alkalinity of the culture medium, within the pH range of bacterial growth. 4. Many substances which may affect the action of other antimicrobial agents had no important effect on the action of erythromycin. 5. Erythromycin inhibiting substances could not be demonstrated in cultures of erythromycin-resistant bacteria. 6. The size of the inoculum affected the results of sensitivity tests with erythromycin, but there was considerable tolerance within the range of inocula used in clinical testing. 7. The broth-dilution and agar-plate dilution methods generally gave comparable results in tests for sensitivity of bacteria to erythromycin but the values obtained by the agar method often were higher, particularly with some coliform organisms. 8. Tests done on more than 1000 bacterial strains, most of them recently isolated from patients, indicated that erythromycin was most active against the Gram-positive cocci and was quite active against strains of Neisseria, diphtheria bacilli and Hemophilus, but for practical purposes it could be considered inactive against most coliform and enteric bacilli. 9. Concentrations of erythromycin in plasma after single oral doses varied widely but in general were proportional to the dose. Maximum concentrations were found 1 or 2 hours after a dose, and no activity was demonstrated at 6 hours except following doses of 1.0 g. Significant concentrations were maintained in the plasma with oral doses of 250 mg or more every 3 or 4 hours. 10. The amounts of erythromycin activity recovered in the urine appeared to be small and erratic after ingestion of single doses or after repeated small doses, particularly early in the course of therapy; however, on continuous therapy with divided doses, up to 15% of the amount ingested daily could be demonstrated in active form in the urine. Results of studies on the mode of action of erythromycin and on the resistance of bacteria to that agent are presented in the succeeding papers.