Two hundred and forty-nine patients with monomicrobial bacteraemia due to third-generation cephalosporin (TGC)-resistant Citrobacter freundii (42), E. aerogenes (23), E. cloacae (143), and Serratia marcescens (41) were analyzed for antibiotic therapy used and outcome. For isolates with resistance to any of the TGCs, all beta-lactams, except imipenem, were considered ineffective. Of 152 patients given appropriate treatment, the mortality rates were 10.9% for 128 patients given monotherapy and 25.0% for 24 patients given combination therapy (P=0.09). Of patients given monotherapy, there were no significant differences in mortality between imipenem, aminoglycoside, and ciprofloxacin treatment groups (P=0.57). Only shock was associated with mortality in multivariate analysis. In conclusion, for patients with TGC-resistant Gram-negative bacteraemia, no significant difference in outcome was observed between single antibiotic therapy groups or monotherapy and combination therapy groups.