Implementation and Impact of an Antimicrobial Stewardship Post-Prescription Review Program: Challenges Amid Rising Resistance in a Tertiary Hospital

Background Antimicrobial resistance (AMR) represents a major global health emergency. This study evaluated a pilot Antimicrobial Stewardship (AMS) program based on post-prescription review of selected antibiotics at Fondazione IRCCS Policlinico San Matteo in Pavia, Italy. Methods This quasi-experimental study analysed the first six months (March-August 2024) of an AMS program in Internal Medicine, General Surgery, and Hematology departments. The intervention focused on post-prescription review of carbapenems, new beta-lactam/beta-lactamase inhibitors, and cefiderocol. Multiple outcome measures were assessed, including prescription appropriateness, intervention effects, microbiological patterns, antibiotic consumption, and costs, with comparison to the corresponding period in 2023. Results We analysed 210 antibiotic prescriptions (64 in Internal Medicine, 40 in General Surgery, 106 in Hematology). Overall appropriateness was 50.0% (95% CI: 43.2–56.8%), with therapy duration being the principal factor of inappropriateness (75.0% of inappropriate cases). Inappropriate therapy was associated with a significantly higher risk of unfavourable outcomes (χ2 = 9.41; p = 0.002) and longer hospital stays (median difference: 2 days; p < 0.001). Antibiotic consumption increased significantly (+ 41.93%), primarily in Hematology (+ 54.17%), with overall costs rising by 56.12%. The prevalence of multidrug-resistant organisms increased substantially, with NDM-producing Klebsiella spp. showing increases in both colonization (+ 77.58%) and infection (+ 95.10%). There was a significant association between inappropriate prescriptions and subsequent modification (χ²=6.42; p = 0.011), more evident for targeted than for empirical therapies. Conclusions The pilot AMS program identified significant challenges in optimizing antibiotic use amid increasing resistance rates. Department-specific responses suggest tailored approaches may be more effective than uniform strategies. Enhanced infection control, targeted economic stewardship, and an improved handshake model of intervention are recommended to improve future outcomes.