An in vitro model simulating amoxicillin and cefotaxime concentrations in human serum (after standard doses) was used to explore the activities of these drugs over time against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae strains. An initial inoculum reduction percentage of > or = 90% was obtained with amoxicillin and maintained for 2 to 8 h, regardless of the strain tested. In contrast, experiments showed that cefotaxime had significantly (P < 0.001) less capability to reduce initial inocula of the penicillin-resistant pneumococci from 0.5 h on than amoxicillin, despite the same in vitro susceptibility to amoxicillin and cefotaxime in both strains.