A contemporary collection of 12737 strains from pediatric patients (<18 years) isolated over a 7-year period (1998-2004) from 52 sentinel hospitals in North America was tested to determine the comparative antimicrobial potency of broad-spectrum parenteral cephalosporins and selected comparator agents. Most of the strains (84.1%) were isolated from blood stream or respiratory tract infections. The rank order of the top 10 pediatric pathogens analyzed was Streptococcus pneumoniae (15.5%) >Haemophilus influenzae (14.6%) >Staphylococcus aureus (13.8%) >Moraxella catarrhalis = coagulase-negative staphylococci (8.0%) >Escherichia coli (7.8%) >Pseudomonas aeruginosa (5.2%) >Klebsiella spp. (4.8%) >Enterococcus spp. (4.7%) > beta-hemolytic streptococci (4.4%). Both cefepime and ceftriaxone (MIC(90), 1 microg/mL; 93.9% and 93.7% susceptible, respectively) were highly active against S. pneumoniae. However, the S. pneumoniae strains showed reduced susceptibility to ceftazidime (56.6%), as well as penicillin (56.6%) < trimethoprim-sulfamethoxazole (57.1%) < erythromycin (66.2%) < tetracycline (71.4%). beta-Hemolytic streptococci showed 100.0% susceptibility to penicillin, cefepime, and ceftriaxone. Cefepime and ceftriaxone exhibited high activity against oxacillin (methicillin)-susceptible S. aureus, (MIC(90), 4 microg/mL; 100.0% and 99.8% susceptible, respectively), whereas ceftazidime (MIC(90), 16 microg/mL) was active against only 86.7% of strains. H. influenzae strains showed complete susceptibility to cefepime, ceftriaxone, and levofloxacin (MIC(90), < or =0.5 microg/mL; 100.0%), and 34.0% of H. influenzae and 99.2% of M. catarrhalis strains produced beta-lactamase. Although the 3 cephalosporins tested (cefepime, ceftriaxone, and ceftazidime) were very active (98.6-99.6% susceptible) against E. coli, cefepime (99.0% susceptible) was slightly more active than ceftriaxone and ceftazidime (96.4% and 95.1% susceptible, respectively) against Klebsiella spp. Cefepime was also the most active beta-lactam agent tested against Enterobacter spp. (MIC(90), 2 microg/mL; 99.3% susceptible), whereas the susceptibility rates of other broad-spectrum beta-lactams (ceftriaxone, ceftazidime and piperacillin-tazobactam) were significantly lower (78.4-81.5%). Against P. aeruginosa, imipenem and piperacillin-tazobactam showed the highest susceptibility rates (94.4% and 93.3%, respectively), whereas imipenem and cefepime showed the lowest resistance rates (1.4% and 2.3%, respectively). Our results indicate that cefepime was the most broad-spectrum cephalosporin analyzed and remains a very potent alternative for the treatment of contemporary pediatric infections in North America.