A university hospital formulary change that was designed to reduce the use of the third-generation cephalosporins ceftazidime and cefotaxime and replace them with the so-called "fourth-generation" cephalosporin cefepime was evaluated. A retrospective review of antibiotic use and antimicrobial resistance during two 6-month periods before and after the formulary change was performed. All hospital patients with vancomycin-resistant Enterococcus (VRE), ceftazidime-resistant Klebsiella pneumoniae (CRKP), methicillin-resistant Staphylococcus aureus (MRSA), piperacillin-resistant Pseudomonas aeruginosa (PRPA), and ceftazidime-resistant P aeruginosa (CRPA) infections were included in the study. Ceftazidime use decreased from 9600 g to 99 g, and cefotaxime use decreased from 6314 g to 732 g, which represented a combined decrease of 89%. Use of cefepime increased from 0 g to 5396 g. Infections from CRKP decreased from 13% to 3%, PRPA infections decreased from 22% to 14%, and CRPA infections decreased from 25% to 15% (p <0.05 for all). Infections from MRSA dropped insignificantly, and VRE infections increased significantly. Substituting cefepime for ceftazidime and cefotaxime while reducing the overall use of cephalosporins appears to decrease rates of CRKP, PRPA, and CRPA.