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A prospective audit and feedback antimicrobial stewardship intervention conducted in the Orthopaedics Department of a university hospital in Portugal was evaluated by comparing an interrupted time series in the intervention group with a non-intervention (control) group. Monthly antibiotic use (except cefazolin) was measured as the World Health Organization's Anatomical Therapeutic Chemical defined daily doses (ATC-DDD) from January 2012 to September 2016, excluding the 6-month phase of intervention implementation starting on 1 January 2015. Compared with the control group, the intervention group had a monthly decrease in the use of fluoroquinolones by 2.3 DDD/1000 patient-days [95% confidence interval (CI) −3.97 to −0.63]. An increase in the use of penicillins by 103.3 DDD/1000 patient-days (95% CI 47.42 to 159.10) was associated with intervention implementation, followed by a decrease during the intervention period (slope = −5.2, 95% CI −8.56 to −1.82). In the challenging scenario of treatment of osteoarticular and prosthetic joint infections, an audit and feedback intervention reduced antibiotic exposure and spectrum. [ABSTRACT FROM AUTHOR]