Effectiveness and safety of strategies to optimise antimicrobial use in solid organ transplant recipients. Systematic review and meta-analyses.

Background: Solid organ transplant recipients (SOTr) are at high risk of infectious complications, and effective antimicrobial stewardship (AMS) programmes need to be developed. We aimed to review the available evidence on the effectiveness and safety of different strategies to optimise antibiotic use in SOTr. Methods: In our systematic review and meta-analyses, we searched MEDLINE (via PubMed), EMBASE, and SCOPUS for original research articles published up to 06 March 2025.Studies with a control group evaluating different strategies to optimise antimicrobial use in adult SOTr were included. The outcomes assessed were mortality, transplant-related complications, infectious outcomes, development of antimicrobial resistance, antimicrobial consumption, hospital related variables, and antimicrobial toxicities. A risk-of-bias assessment was performed using the Cochrane EPOC group's criteria. Data from included studies were pooled in meta-analyses if three or more studies had the same type of intervention and comparison group and reported sufficient data on infection outcomes to be combined. Meta-analyses were performed using a random-effects model and the inverse variance method with the I Findings: Of the 4050 articles identified, 34 studies met the inclusion criteria. Seventeen studies addressed perioperative antimicrobial prophylaxis (seven of which evaluated specifically duration of antimicrobial prophylaxis), two reported information about decolonisation strategies, three addressed duration of antimicrobial treatment as target therapy, one evaluated antibiotic oral step-down strategy, and six reported the impact of AMS implementation approach on SOTr. The other five studies evaluated specific targeted prophylaxis. All the studies had a moderate or high risk of bias. The meta-analysis of three studies on the effect of AMS programmes showed that this intervention may reduce the rate of surgical site infections (OR 0·57, 95% CI 0·35-0·94). For perioperative antimicrobial prophylaxis, the meta-analysis of six trials showed results in favour of prophylaxis in terms of reducing surgical site infections (risk ratio 1·93, 95% CI 1·14-3·27) in kidney SOTr, but prolonging prophylaxis beyond 24 h was not associated with improved SSI rates (RR 0·87, 95% CI 0·51-1·48). Regarding the duration of antimicrobial treatment for uncomplicated graft-related infections (liver and kidney SOTr), the meta-analyses found no difference in terms of recurrence between short and long antimicrobial regimens (0·86, 95% CI 0·55-1·34). The four meta-analyses had low heterogeneity between studies. Interpretation: Strategies to optimise antimicrobial use are safe, with no negative impact on mortality or transplant-related complications, and appear to improve some clinical outcomes in SOTr, particularly when using perioperative antimicrobial prophylaxis in kidney SOTr and when implementing AMS programmes. No difference in the rate of surgical site infection was found between short and extended duration of antimicrobial prophylaxis for kidney and liver SOTr. This suggests that a shorter duration of antimicrobial surgical prophylaxis may be safe for transplant recipients. Short courses of antibiotics were not associated with an increased rate of relapses for uncomplicated graft infections, according to observational studies pooled in our meta-analysis. However, further high-quality clinical trials are needed to better understand the effects of these strategies in SOTr and to design optimal AMS interventions in this population. Funding: This study was supported by the