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The increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae will probably trigger a rise in the use of carbapenems. The effect of these antibiotics on the risk of involvement of ESBL-producing organisms in serious infections is unclear.Retrospective analysis of 2172 episodes of healthcare-associated bacteraemia diagnosed during a 3 year period in a teaching hospital. Putative risk factors included demographics, co-morbidities, previous isolation of an ESBL-producing organism and exposure to antibiotics. Univariate and multivariate analysis of the association of risk factors with ESBL-producing organisms was performed in the entire series of bacteraemic episodes and in those due to Escherichia coli or Klebsiella spp.In the entire series, prior isolation of an ESBL-producing organism [odds ratio (OR) 5.9 (3.02, 11.5)]; an ultimately/finally fatal co-morbidity [OR 2.8 (1.55, 4.95)]; renal transplantation [OR 4.3 (1.96, 9.63)]; a urinary source [OR 4.2 (2.22, 7.84)]; shock [OR 2.4 (1.35, 4.1)] and previous use of cephalosporins [OR 2.6 (1.54, 4.51)], carbapenems [OR 2.5 (1.24, 5.05)] and glycopeptides [OR 0.4 (0.13, 0.93)] were significantly associated with ESBL-producing E. coli or Klebsiella spp. by multivariate analysis. Prior isolation of an ESBL-producing organism, an ultimately/finally fatal co-morbidity, renal transplantation, and previous use of cephalosporins and carbapenems were also significant in the analysis restricted to episodes due to E. coli or Klebsiella spp.In patients with healthcare-associated bacteraemia, prior use of carbapenems may be only second to cephalosporins as the most significant antibiotic exposure associated with the involvement of ESBL-producing organisms.