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Background and Importance The use of broad-spectrum antibiotics (BSA) contributes to the selection of resistant strains and in many clinical situations, there are narrower-spectrum alternatives available. In the context of an antimicrobial stewardship project, real-time reviews by clinical pharmacists (CP) working alongside infectious diseases specialists (IDS) could improve BSA prescriptionsAim and Objectives Our aim was to improve and reduce the use of BSA in hospital settings by implementing an interdisciplinary intervention involving a clinical decision support system (CDSS) to identify patients on five-day BSA therapies.Material and Methods This multicentre prospective study was conducted in a tertiary teaching hospital and a secondary hospital. Both centres routinely used the same CDSS to screen 799 and 212 beds, respectively, in adult wards. This CDSS identified patients with prescriptions of piperacillin/tazobactam, cefepime, and carbapenems (meropenem, ertapenem, and imipenem/cilastatin) for at least five days. After antibiotic appropriateness assessment, clinical pharmacists could suggest several interventions to prescribers or to IDS, using decision making algorithms validated by both CP and IDS for each BSA class. When appropriate, IDS provided consultations to prescribers.Results Over a 6-month period, the BSA therapies of 442 patients were assessed. Among them, 61% were admitted to surgical wards and 61% had previously received an IDS consultation. The most frequent indications for BSA treatment were intra-abdominal infections (33%), community- or hospital-acquired pneumonia (17%), community- or hospital-acquired urogenital infections (10%), and skin and soft tissue infections (10%). Following the CP’s assessment, 174 interventions were made either directly to the prescriber (30%) or through an IDS consult (70%) and 141 (81%) were accepted and implemented within 24 hours. On average, the CP spent 17 ± 5 minutes per patient and the IDS 15 ± 7 minutes. The most frequent interventions proposed were defining an antibiotic treatment duration (26%), stopping antibiotic treatment (21%), referring to an IDS (18%), and de-escalating antibiotics (16%). This interdisciplinary intervention improved 32% of BSA therapies for the 442 patients included.Conclusion and Relevance Our study demonstrated that an intervention driven by a CDSS and led by clinical pharmacists in collaboration with infectious disease specialists is an effective approach to improve and to reduce the use of broad-spectrum antibiotics in a hospital setting.Conflict of Interest No conflict of interest