Time course of the antibacterial activity of erythromycin stearate and erythromycin acistrate against two Staphylococcus aureus strains in vitro

The antibacterial efficacy of erythromycin stearate (ES) and a new erythromycin prodrug, erythromycin acistrate (EA, 2'-acetyl erythromycin stearate), was compared in two Staphylococcus aureus strains, one sensitive and the other resistant to erythromycin. The growth was continuously monitored turbidometrically for 24 h. With the sensitive S. aureus, the inhibitory effects of both ES and EA were visible within 1-2 h when the antibiotics were added at 0 or 1.5 h after the beginning of the incubation. When they were added at 3 h, their action was immediate at 0.5 and 1 mg/l, and 5 mg/l caused a complete inhibition of the growth. At 0.5 and 1 mg/l, however, ES was much more effective than EA. When EA and ES (1, 5 or 10 mg/l) were added at 0 or 1.5 h to the resistant staphylococcal culture, the lag phases (no detectable growth) were prolonged as a function of drug concentration but eventually the growth was restored. The action of EA was weaker and the lag phases were 2-5 h shorter than those after ES. When the compounds were added at 3 h, the antibacterial effect was visible immediately. The increase of absorbance was slowed down even by 1 mg/l of ES and almost prevented by 5 mg/l. At these concentrations EA was less effective than ES, but the two erythromycins were equally active at 10 mg/l. These results show that addition of EA acts on both staphylococci as rapidly as addition of ES but to a lesser extent. Evidently EA is antibacterially weaker than ES, or rapidly hydrolyzed to erythromycin after it has been added to the test system.