Escherichia coli is the leading cause of bloodstream infections (BSIs) caused by Gram-negative bacteria. The increasing prevalence of antibiotic-resistant E. coli strains, particularly those producing extendedspectrum -lactamases (ESBLs), increases the odds that empirically prescribed antimicrobial therapy for these infections will be inadequate, but the economic impact of this risk has not been fully evaluated. In the present retrospective 1-year analysis of 134 consecutive E. coli BSIs in our hospital, we explored the clinical and economic impacts of (i) inadequate initial antimicrobial treatment (IIAT) (i.e., empirical treatment with drugs to which the isolate had displayed in vitro resistance) of these infections and (ii) ESBL production by the bloodstream isolate. Cost data were obtained from the hospital accounting system. Compared with the 107 (79.8%) adequately treated patients, the 27 (20.1%) who received IIAT had a higher proportion of ESBL BSIs (74.0% versus 15.8%), longer (؉6 days) and more costly (؉EUR 4,322.00) post-BSI-onset hospital stays, and higher 21-day mortality rates (40.7% versus 5.6%). Compared with the 97 non-ESBL infections, the 37 (27.6%) ESBL BSIs were also associated with longer (؉7 days) and more costly (؉EUR 5,026.00) post-BSI-onset hospital stays and increased 21-day mortality (29.7% versus 6.1%). These findings confirm that the hospital costs and mortality associated with E. coli BSIs are significantly increased by ESBL production and by IIAT.Escherichia coli is the leading cause of bloodstream infections (BSIs) involving Gram-negative bacteria (16, 37). The last 20 years have witnessed a striking increase in the number of infections caused by antibiotic-resistant strains of E. coli, and this has had an important impact on the outcomes of BSIs (24). Multidrug-resistant (MDR) E. coli strains and particularly those that produce extended-spectrum -lactamases (ESBL) not only are endemic in many health care settings but also have become an important cause of communityacquired infections (1,27,28). These organisms are resistant to many of the antimicrobial agents usually recommended for the treatment of infections caused by E coli, so the odds are quite high that empirically prescribed antimicrobial therapy will be ineffective against these infections (4,9,18,22,23,25,26, 29,32,35).Our previous studies showed that failure to provide prompt, effective antimicrobial therapy for BSIs caused by ESBL-producing E. coli is associated with increased mortality and longer hospital stays (35, 36). Similar findings have been reported by others (15,18,20,24,31,32). Length of stay (LOS) has been identified as the single most important determinant of costs related to inpatient care for bacteremia (3). Inadequate initial antimicrobial therapy (IIAT) has been shown to increase hospitalization costs related to intra-abdominal and other sterilesite infections caused by methicillin-resistant Staphylococcus aureus (33), but this issue has not been specifically explored with reference to BSIs caused by E....