Rapid Microbiological Diagnostics for Sepsis: Narrative Review of Current and Prospective Approaches

In this review, we aim to provide critical care clinicians with a concise introduction to the current and prospective tools that exist for rapid diagnostics in sepsis employed in the microbiology laboratory. Our objective is to provide a primer for clinicians to engage with their colleagues in the microbiology laboratory for the selection and implementation of new and emerging tools.

The primary literature, restricted to peer-reviewed sources, was queried using relevant search terms (e.g., sepsis, rapid diagnostics, microbiology, etc) using PubMed and Google Scholar (until February 2025), as well as review of citations of relevant articles.

After initial searches, literature was screened by each author responsible for the sections of this review: blood culture-based methods (L.B.H.), nonblood culture-based molecular diagnostics (D.L.), and antigen-based methods (Z.N.S.). Titles and abstracts of individual articles were reviewed by the respective section authors and articles describing microbiological diagnostic techniques that decrease the turnaround time for the identification of microorganisms and/or antimicrobial susceptibility testing with relevance to the diagnosis of sepsis were retained.

Data from individual studies was extracted by each respective section author using Zotero reference management software and synthesized narratively.

Rapid diagnostics for sepsis can be broadly divided into three categories: those applied to incubated positive blood culture specimens, and culture-independent approaches applied directly to clinical specimens, which can be further divided into those based on the direct detection of the nucleic acids of microorganisms, and those based on the detection of antigens. Blood culture-based approaches rely on biological amplification of microorganisms present but aim to measure this amplified signal directly to speed identification of microorganisms or antimicrobial resistance relative to traditional plate-culture-based workflows. Nucleic acid and antigen detection methods can be performed directly on clinical specimens, and so promise more rapid diagnostics in sepsis, but with method-specific tradeoffs in sensitivity, specificity, and interpretation.

Evolutionary refinements of blood culture-based diagnostic approaches have decreased time to actionable information significantly while emerging and established culture-independent approaches can reduce time to actionable information to a few hours. In aggregate these interventions may have important clinical benefits, yet significant heterogeneity exists in the applicability and availability of technologies.