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Many strategies and technologies are available to improve blood culture (BC)-based diagnostics. The ideal approach to BCs varies between healthcare institutions. Institutions need to examine clinical needs and practices in order to optimize BC-based diagnostics for their site. Before laboratories consider offering rapid matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) or expensive rapid panel-based molecular BC diagnostics, they should optimize preanalytical, analytical, and postanalytical processes and procedures surrounding BC systems. Several factors need to be considered, including local resistance rates, antibiotic prescribing patterns, patient- and provider-types, laboratory staffing, and personnel available to liaise with clinicians to optimize antibiotic use. While there is much excitement surrounding new high-technology diagnostics, cost-neutral benefits can be realized by optimizing existing strategies and using available tools in creative ways. Rapid BC diagnostics should be implemented in a manner that optimizes impact. Strategies to optimize these BC diagnostics in individual laboratories are presented here. [ABSTRACT FROM AUTHOR]