Multiple modes of interventions are available when implementing an antibiotic stewardship program (ASP), however, their complementarity has not yet been assessed. In a 938-bed hospital, we sequentially implemented four combined modes of interventions over one year, centralized by one infectious diseases specialist (IDS): (1) on-request infectious diseases specialist consulting service (IDSCS), (2) participation in intensive care unit meetings, (3) IDS intervention triggered by microbiological laboratory meetings, and (4) IDS intervention triggered by pharmacist alert. We assessed the complementarity of the different cumulative actions through quantitative and qualitative analysis of all interventions traced in the electronic medical record. We observed a quantitative and qualitative complementarity between interventions directly correlating to a decrease in antibiotic use. Quantitatively, the number of interventions has doubled after implementation of IDS intervention triggered by pharmacist alert. Qualitatively, these kinds of interventions led mainly to de-escalation or stopping of antibiotic therapy (63%) as opposed to on-request IDSCS (32%). An overall decrease of 14.6% in antibiotic use was observed (p = 0.03). Progressive implementation of the different interventions showed a concrete complementarity of these actions. Combined actions in ASPs could lead to a significant decrease in antibiotic use, especially regarding critical antibiotic prescriptions, while being well accepted by prescribers.