Introduction: Restrictions in prescribing broad spectrum antimicrobials have been part of a strategy to reduce Clostridium difficile cases in the UK in recent years. However, there has been little work on assessing the safety of alternative antimicrobial agents. Methods: We performed an uncontrolled prospective observational survey over a 1-year period to determine the effectiveness and safety of a new antimicrobial stewardship programme in a district hospital in the UK. Results: In total, 227 Gram-negative bacteraemias (203 episodes) occurred in the study period. Guidelines were adequate in 194 of 203 (95%) episodes and 163 episodes (80.2%) received adequate therapy. Patients in the inadequate therapy group had >2-fold increased likelihood of death [odds ratio (OR) = 2.63, 95% confidence interval (CI) = 1.09-6.34] within 30 days and >6-fold increased risk of death (OR = 6.40, 95% CI = 2.22-18.45) within 1 week when compared to patients in the adequate therapy group. Failure to administer gentamicin was the principal reason for not following the guidelines (18 episodes). Eight of these 18 episodes were susceptible to cefuroxime and two of these patients died. Discussion: Adherence to the guidelines was associated with a correct empirical antibiotic choice and reduced mortality. This study also demonstrates the importance of adopting guidelines based on local susceptibility patterns.