Increasing occurrence of drug-resistant S. pneumoniae (DRSP) in children has necessitated reevaluation of susceptibility data and management options. To determine if there are differences in activities among parenteral cephalosporins against DRSP. we tested 38 isolates of penicillin-intermediate (Int) and 28 isolates of penicillin-resistant (Res) 5. pneumoniae obtained from pediatric patients against ceftriaxone, cefotaxime, ceftizoxime and cefuroxime. Minimal inhibitory concentrations (MICs) were determined by microbroth dilution in accordance with 1994 guidelines of the National Committee for Clinical Laboratory Standards, Isolates were primarily from blood, CSF, middle ear and respiratory tract. Predominant serotypes were 6.14,19 and 23. Results of MICs μg/mL). Dug Range Pen-Int MIC50 Pen-Int MIC90 Pen-Int MIC91 Pen-Int MIC90 ceftriaxone ≤ 0.03 - 4 0.12 0.5 1 4 cefotaxime ≤ 0.03 - 16 0.12 0.5 1 8 ceftizoxime < 0.03 - > 64 0.25 2 16 64 cefuroxime < 0.03 - 32 0.5 2 8 32 All Pen-Int isolates were susceptible to ceftriaxone and cetotaxime (MIC < 0.5 μg/mL). MIC90s were 2 2-fold dilutions < cefuroxime and ceftizoxime. All drugs were less active against Pen-Res strains. The ceftriaxone MIC90 was I dilution < cefotaxime. MIC90s for ceftroxinie and ceftizoxime were 3 and 4 dilutions > ceftiroxone, respectively. This study confirms that ceftriaxone and cefotaxime are more active than cefuroxime and ceftizoxime against Pen-Int and Pen-Res S. pneumoniae isolated from children. Since some MICs for cefuroxime and ceftizoxime approached achievable serum concentrations, neither should be used empirically in populations where DRSP is known to occur.