In a previous study, we demonstrated that rapid antibiotic susceptibility tests (ASTs) can be performed directly on blood culture samples tested on Mueller–Hinton Rapid agar (MHR-SIR) with a time delay of 6–8 h. Using this rapid disc diffusion method, we analysed the clinical impact associated with rapid reporting of results in our hospital setting. All patients with bloodstream infections (BSIs) related to Enterobacteriaceae or Staphylococcus aureus were prospectively included in the study. The rapid ASTs were performed by incubation of positive blood cultures on MHR-SIR for 6–8 h by direct inoculation according to BSAC recommendations. One hundred and sixty-seven patients with BSIs were included as MHR-guided adaptation therapy cases. Eighty percent had Enterobacteriaceae-related BSIs, of which 12 (9%) were ESBL producers and 20% were S. aureus-related BSIs. A urinary or intra-abdominal infection was observed in 44.3% and 19.8%, respectively, of Enterobacteriaceae-related infections. The most frequent sources of infections for S. aureus BSIs were cutaneous and endovascular, in 43% and 23% of cases, respectively. Forty-four percent of the patients benefited from therapeutic modification according to the results of the MHR-SIR AST. Thus, empirical antibiotic therapy was modified by using antibiotic therapy that had too wide a spectrum or was unsuitable in 26% and 18% of cases, respectively. Compared with the 24 h required for the reference method, the median length of time to provision of susceptibility test results by MHR-SIR was 7 h. This study showed a significant time saving (17 h) on the appropriateness of antibiotic prescription and demonstrated a significant impact regarding the choice and reduction of the spectrum of antibiotic therapy.