In vitro antagonism between beta-lactam and macrolide in Streptococcus pneumoniae: how important is the antibiotic order?

We found that the in vitro interaction between penicillin or cefotaxime and erythromycin against Streptococcus pneumoniae varies depending on the order of antibiotic exposure. Time-kill experiments were performed with penicillin, cefotaxime, erythromycin and different order combinations of both beta-lactams with erythromycin. The mean difference between the colony count at 0 and 6h for penicillin, cefotaxime and erythromycin tested separately was 3.5 log cfu/mL, 2.4 and 1.5 respectively for susceptible strains. The mean difference for the combination of beta-lactam and erythromycin studied simultaneously was 1.8 log cfu/mL for these strains. The association of penicillin or cefotaxime with erythromycin added two hours later showed an activity similar to those of beta-lactam alone (mean difference was 3.0 for this association with penicillin and 2.5 with cefotaxime). Therefore, the antagonistic effect of macrolide activity could be less important if erythromycin was administrated after beta-lactam.