To address the public health problem of antimicrobial resistance, the European Union, founded the European Antimicrobial. Resistance Surveillance System. A network of 32 Spanish hospitals, serving approximate to 9.6 million persons, submitted antimicrobial-susceptibility data. on 7,098 invasive Escherichia coli species (2001-2003). Resistance to ampicillin, cotrimoxazole, ciprofloxacin, gentamicin, and tobramycin was found at rates of 59.9%, 32.6%, 19.3%, 6.8%, and 5.3%, respectively. Resistance to multiple drugs increased from 13.8% in 2001 to 20.6% in 2003 (p < 0.0001). Antimicrobial consumption data were obtained from the Spanish National Health System. In spite of decreased cephalosporin and P-lactam use, overall extended-spectrum P-lactamase production increased from 1.6% (2001) to 4.1% (2003) (p < 0.0001), mainly due to the rising prevalence of cefotaximases. Resistance to ciprofloxacin significantly increased, mostly in community-onset infections, which coincided with a rise in community quinolone use. Cotrimoxazole resistance remained stable at approximate to 30%, even though its use was dramatically reduced.