▪Objectives: To study the effect of previously administered antibiotics on the antibiotic susceptibility profile of Enterobacter, the factors affecting mortality, and the emergence of antibiotic resistance during therapy for Enterobacter bacteremia.

▪Design: Prospective, observational study of consecutive patients with Enterobacter bacteremia.

▪Setting: Three university tertiary care centers, one major university-affiliated hospital, and two university-affiliated Veterans Affairs medical centers.

▪Patients: A total of 129 adult patients were studied.

▪Measurements: The two main end points were emergence of resistance during antibiotic therapy and death.

▪Main Results: Previous administration of third-generation cephalosporins was more likely to be associated with multiresistant Enterobacter isolates in an initial, positive blood culture (22 of 32, 69%) than was administration of antibiotics that did not include a third-generation cephalosporin (14 of 71, 20%; P < 0.001). Isolation of multiresistant Enterobacter sp. in the initial blood culture was associated with a higher mortality rate (12 of 37, 32%) than was isolation of a more sensitive Enterobacter sp. (14 of 92, 15%; P = 0.03). Emergence of resistance to third-generation cephalosporin therapy (6 of 31, 19%) occurred more often than did emergence of resistance to aminoglycoside (1 of 89, 0.01%; P = 0.001) or other beta-lactam (0 of 50; P = 0.002) therapy.

▪Conclusions: More judicious use of third-generation cephalosporins may decrease the incidence of nosocomial multiresistant Enterobacter spp., which in turn may result in a lower mortality for Enterobacter bacteremia. When Enterobacter organisms are isolated from blood, it may be prudent to avoid third-generation cephalosporin therapy regardless of in-vitro susceptibility.