Enhancing detection and management of bloodstream infection and/or sepsis caused by multi-drug resistant microorganisms integrating rapid molecular diagnostic tests and culture-based methods. A living Evidence Synthesis.

Background: Sepsis caused by multidrug-resistant organisms (MDROs) poses significant diagnostic and therapeutic challenges. Rapid diagnostic tests, including nucleic acid amplification tests (NAATs), in Situ Hybridization-Based Methods and Mass Spectral Methods have emerged as promising tools to improve time to detection and guide early, appropriate treatment.Objective: To establish a baseline synthesis of the current evidence on the diagnostic accuracy and clinical impact of molecular diagnostic tests for sepsis due to MDROs. Methods: We performed a living evidence systematic review. Searches were conducted in the Epistemonikos L·OVE platform without restrictions. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using AMSTAR II, and certainty of evidence with GRADE. Diagnostic accuracy and clinical outcomes were narratively synthesized due to heterogeneity. Subgroup and sensitivity analyses were planned. The evidence will be updated bi-monthly throughout the 12-month LES cycle.Results: Three systematic reviews were included, covering diagnostic and clinical outcomes of rapid molecular tests versus culture-based methods in patients with suspected bloodstream infections or sepsis caused by MDROs. NAATs showed high specificity and moderate-to-low sensitivity for MSSA and MRSA detection, with better performance in ruling out infections. Clinical outcomes suggested shorter time to appropriate treatment and reduced hospital stay, though effects on mortality were inconsistent. Certainty of evidence ranged from moderate to very low due to study heterogeneity and risk of bias.Conclusion: Rapid molecular tests show high specificity and potential to reduce time to appropriate treatment in sepsis caused by MDROs, particularly MSSA and MRSA. However, their diagnostic sensitivity is variable, and evidence on clinical outcomes remains limited and of low certainty. Further high-quality research is needed to confirm their impact on patient management and outcomes.