Broth microdilution testing was used to study the activity of several beta-lactam antimicrobial agents, including piperacillln-tazobactam and cefepime, against 108 clinically derived Escherichia coli and Klebsiella sp. strains resistant to oxyimino cephalosporins (i.e., putative extended- spectrum β-lactamase producers). On the basis of the percentage of susceptible strains, imipenem (100%), cefotetan (≥92%), and piperacillin- tazobactam (≥86%) were the most active agents. Cefepime activity (52 to 64% susceptible) was comparable to that of cefotaxime (40 to 63% susceptible) and aztreonam (20 to 63% susceptible). Among all beta-lactams tested, imipenem and cefotetan demonstrated the highest and most consistent level of activity and were the least affected by challenges with increased sizes of inocula of these resistant organisms.