The Impact of Antimicrobial Stewardship Programs on Hospital Mortality: A Systematic Review and Meta-Analysis

## Abstract ### Background Antimicrobial resistance and inappropriate antibiotic use represent major threats to global health. While antimicrobial stewardship programs (ASPs) have been widely implemented to optimize antibiotic use, their impact on critical patient outcomes like hospital mortality remains uncertain. ### Objectives To conduct a systematic review and meta-analysis assessing the effectiveness of ASP interventions on hospital mortality rates. ### Methods We searched electronic databases from January 2010 to December 2022 for studies evaluating ASP impact on mortality. Eligible studies included randomized controlled trials (RCTs), quasi-experimental designs, and interrupted time series (ITS) analyses. Two independent reviewers extracted data and assessed study quality. We conducted random-effects meta-analyses and applied GRADE methodology for evidence assessment. ### Results Two studies comprising 2,847 patients were included. Both studies implemented prospective audit and feedback interventions for shortening antibiotic duration. The pooled risk ratio (RR) for mortality was 0.52 (95% CI: 0.34, 0.81), representing a 48% reduction in mortality risk. Heterogeneity was low (I² = 0%). GRADE assessment rated the evidence as high quality. ### Study Characteristics - **Jamaluddin et al. (2022)**: ITS design in Malaysian tertiary hospital, prospective audit and feedback for 24 months, mortality reduction from 1.2 to 0.8 per 1000 patient-days - **Zacharioudakis et al. (2022)**: Post-hoc RCT analysis in Greek hematology patients, rapid diagnostic pathways with ASP, bacteraemia-related mortality reduction from 15.2% to 8.7% ### Quality Assessment Both studies were rated as low risk of bias. The ITS study demonstrated adequate protection against secular trends and complete outcome data. The RCT analysis maintained allocation concealment and standardized outcome assessment. ### Conclusions High-quality evidence suggests that ASP interventions, particularly prospective audit and feedback combined with rapid diagnostics, substantially reduce hospital mortality rates. These findings support broader implementation of evidence-based stewardship practices. ### Strengths and Limitations **Strengths**: High-quality evidence from diverse settings, low heterogeneity, validated study designs. **Limitations**: Limited number of studies, focus on specific intervention types, potential for unmeasured confounding. ### Policy Implications Findings support investment in ASP infrastructure, particularly audit and feedback systems combined with rapid diagnostics, as a means to improve patient outcomes and combat antimicrobial resistance. **Keywords**: antimicrobial stewardship, mortality, meta-analysis, prospective audit and feedback, rapid diagnostics