Epidemiological studies have shown a link between carbapenem use and resistance; however, the clinical relationship between antibiotic consumption and the epidemiology of carbapenem-intermediate or -resistant Enterobacteriaceae (CIRE) remains unclear. This study sought to analyze temporal antibiotic consumption trends for relationships with incident CIRE. In total, 310,892 days of therapy and 55 deduplicated CIRE were analyzed. When conservative corrections were applied for multiple comparisons, carbapenem class use and piperacillin-tazobactam use retained significant positive and negative relationships with the incidence of CIRE, respectively.