Diagnostic stewardship for optimizing blood culture practices: a systematic review of clinical practice guidelines and evidence-based recommendations.

Blood cultures (BCs) are fundamental for diagnosing bloodstream infections (BSIs), yet pre-analytical errors and inappropriate use undermine their value. Within the EU-JAMRAI 2 (Second edition of the European Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections) framework, we conducted a systematic review to formulate evidence-based diagnostic stewardship (DS) recommendations for optimizing BC practices across the entire testing pathway, aiming to strengthen antimicrobial stewardship (AMS) programs. Following a scoping review identifying existing documents through 2023, we systematically searched Medline, the Cochrane Library, and grey literature for 2023-2025. From 2440 records, we included 14 clinical practice guidelines and 3 systematic reviews. Methodological quality was assessed using Appraisal of Guidelines for Research and Evaluation II and Assessing the Methodological Quality of Systematic Reviews II tools, and key recommendations were synthesized across all BC phases. Strong consensus emerged on several DS interventions: testing guided by clinical suspicion of sepsis, avoiding routine use in low-yield scenarios; single-site collections sufficient for most cases except endovascular infections; optimal blood volumes (8-10 mL per bottle in adults); and skin antisepsis with 2% chlorhexidine in 70% alcohol. Rapid molecular assays expedite pathogen identification but have limited sensitivity directly from blood. Quality improvement, including contamination monitoring and mandatory training, is essential for sustainability. A key limitation was heterogeneous guideline reporting formats complicating direct comparison. Standardized, evidence-based DS protocols are crucial for accurate BSI diagnosis. This work provides harmonized recommendations applicable across Europe and underscores the urgent need for EU-wide guidelines ensuring consistent, high-quality BC practices that directly strengthen AMS efforts.