In the Netherlands, the issue of antibiotic resistance in case of infections in the hospital mainly concerns extended-spectrum β-lactamase (ESBL) producing Enterobacterales and vancomycin-resistant Enterococcus faecium (VRE). The aims of this thesis were (i) to establish the attributable mortality of ESBL-producing Gram-negatives and VRE in case of infection, and (ii) to investigate the options for predicting the presence of ESBL-producing Gram-negatives when a patient presents with infection. The thesis begins with a meta-analysis (from 2010) of 32 studies comparing mortality between bacteremia with ESBL-producing and non-ESBL-producing Enterobacterales. The pooled unadjusted odds ratio (OR) for mortality associated with ESBL production was 2.35 (95% confidence interval (CI) 1.90–2.91). In the 15 studies that corrected for confounding factors, the adjusted OR was 1.52 (95% CI 1.15–2.01). Among these studies, those that erroneously adjusted for the intermediate variables inappropriate empiric therapy and sepsis severity, reported lower adjusted ORs. Subsequently, non-experimental clinical studies evaluated how well these findings generalize to the Netherlands. In 12% of 1,954 Gram-negative infections occurring between 2013 and 2016 in eight Dutch hospitals, resistant Gram-negatives (mostly ESBL-producing Enterobacterales) were the cause. After adjustment for confounding factors, no increase in 30-day mortality was apparent in case of antibiotic resistance (risk ratio (RR) 1.05, 95% CI 0.46–2.35). A possible explanation is that inappropriate empiric antibiotic therapy, the most likely intermediate on the causal pathway leading from antibiotic resistance to mortality, was not associated with increased mortality. A similar study was performed to establish the attributable mortality of vancomycin resistance in E. faecium bacteremia. In 16 Dutch and 4 Danish hospitals between 2009 and 2014, 63 VRE bacteremias were compared to 234 ampicillin-resistant E. faecium (ARE) bacteremias. The adjusted RR for 30-day mortality ...