MICs and time-kill studies were performed for four clinical isolates of extended-spectrum Beta-lactamase (ESBL)-producing Klebsiella pneumoniae. MICs (mg/L) were: piperacillin/tazobactam 8, cefepime 1-2, meropenem 0.03-0.06, levofloxacin 0.5-8 and tobramycin 0.25-32. For monotherapy, only meropenem maintained bactericidal activity over the 24 h for all isolates. Levofloxacin and tobramycin maintained bactericidal activity against the isolate susceptible to each drug. Piperacillin/tazobactam and cefepime did not maintain bactericidal activity against any isolate. Combination therapy with piperacillin/tazobactam or cefepime combined with levofloxacin or tobramycin were able to provide dramatic killing against ESBL K. pneumoniae, but did not always maintain bactericidal activity. Future studies should evaluate different antimicrobial combinations against pathogens producing specific ESBL enzymes to define their utility as an alternative to carbapenems.