Clinical Efectiveness of a Multiplex PCR-Based Rapid Diagnostic Method in Bloodstream Infections

Condition(s) studied

Investigational drug(s) / intervention(s)

Multiplex PCR-Based Rapid Diagnostic Test: The intervention consists of a real-time multiplex polymerase chain reaction (PCR)-based in vitro diagnostic test applied directly to positive blood culture bottles. Following detection of a positive blood culture signal, an aliquot of the sample is processed for rapid nucleic acid extraction and analyzed using a multiplex PCR panel designed to identify predefined bacterial and fungal pathogens and selected antimicrobial resistance genes. Test results are available within approximately one hour and are reported to the treating clinical team. The multiplex PCR results may be used to inform antimicrobial treatment decisions, including escalation, de-escalation, or optimization of therapy, in conjunction with standard microbiological findings.

Standard Microbiological Diagnostic Methods: Standard microbiological diagnostics include routine processing of positive blood cultures according to institutional practice. This consists of Gram staining, subculture on appropriate agar media, organism identification using conventional and automated methods, and antimicrobial susceptibility testing performed using standardized techniques. Results are reported to the clinical team as they become available and guide antimicrobial management according to usual care.

Study summary

Bloodstream infections (BSIs) are associated with high morbidity and mortality, and delays in initiating appropriate antimicrobial therapy significantly worsen clinical outcomes. Conventional culture-based microbiological methods require 24-72 hours to provide definitive pathogen identification and antimicrobial susceptibility results, often leading to prolonged use of broad-spectrum empirical therapy. Rapid multiplex PCR-based diagnostic tests have the potential to shorten diagnostic timelines by identifying pathogens and resistance genes within approximately one hour; however, data on their real-world clinical impact remain limited.

This prospective, randomized, controlled, single-center study aims to evaluate the clinical effectiveness and diagnostic performance of a multiplex PCR-based rapid diagnostic method applied directly to positive blood culture bottles in adult patients with bloodstream infections. A total of 300 patients (≥18 years) with positive blood culture signals will be randomized 1:1 to either a study group or a control group. In the study group, positive blood cultures will be analyzed using both standard microbiological methods and a multiplex PCR panel, while the control group will undergo standard microbiological diagnostics alone.

The primary endpoint is time to optimal antimicrobial therapy (OTT), defined as the time from blood culture collection to initiation of the narrowest-spectrum, guideline-recommended antimicrobial agent active against the identified pathogen. Secondary endpoints include time to effective antimicrobial therapy (ETT), time to pathogen identification, antimicrobial escalation or de-escalation rates, length of hospital stay, total duration of antimicrobial therapy, and 28-day all-cause mortality.

Clinical, demographic, and microbiological data will be collected prospectively, including comorbidity indices and severity scores. Randomization will be stratified by ICU versus ward admission, presence of neutropenia, and Charlson Comorbidity Index to ensure balanced groups. Diagnostic accuracy of the multiplex PCR panel will be assessed by calculating sensitivity, specificity, predictive values, and agreement with standard culture methods.

This study seeks to determine whether rapid multiplex PCR diagnostics can meaningfully improve antimicrobial stewardship and clinical outcomes in patients with bloodstream infections compared with conventional diagnostic workflows.

Eligibility

Primary outcome measure(s)

• Time to Optimal Antimicrobial Therapy — Through hospitalization, up to 28 days
  Time from blood culture collection to administration of the first dose of the narrowest-spectrum, guideline-recommended first-line antimicrobial therapy active against the isolated microorganism.

Trial sites (1)

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