Overview
The goal of this clinical trial is to learn whether integrating rapid multiplex molecular microbiology results with predefined clinical and laboratory criteria into an antimicrobial stewardship program improves antimicrobial use in hospitalized adults receiving empiric high-impact antimicrobial therapy.
The main questions it aims to answer are:
Does this strategy reduce the duration of exposure to high-impact antimicrobial therapy compared with standard antimicrobial stewardship practice? Does this strategy improve the appropriateness of antimicrobial treatment? Does this strategy affect clinical outcomes, including hospital readmission, intensive care unit admission, infection recurrence, mortality, and healthcare costs? Researchers will compare a protocolized antimicrobial stewardship strategy that incorporates multiplex molecular microbiology results and predefined clinical criteria with the standard antimicrobial stewardship strategy currently used in the hospital.
Participants will:
Receive antimicrobial management according to the stewardship strategy assigned to their hospital unit during the study period.
Undergo molecular microbiology testing and routine clinical and laboratory assessments as part of standard hospital care when indicated.
Be followed to evaluate antimicrobial exposure, treatment appropriateness, safety outcomes, hospital readmission, intensive care unit admission, infection recurrence, mortality, and healthcare costs.
Description
Antimicrobial resistance is one of the greatest challenges facing modern healthcare and is largely driven by inappropriate antimicrobial use. Antimicrobial stewardship programs (ASPs) have become a cornerstone strategy to optimize antimicrobial prescribing and reduce the emergence of antimicrobial resistance. However, antimicrobial decision-making is frequently limited by delays in microbiological diagnosis, often resulting in prolonged exposure to broad-spectrum antimicrobial therapy.
Recent advances in multiplex molecular microbiology allow rapid identification of pathogens and resistance markers directly from clinical samples, frequently several days earlier than conventional microbiological methods. Despite their excellent diagnostic performance, evidence supporting their impact on antimicrobial use and patient outcomes remains inconsistent. Most previous studies have focused on the diagnostic accuracy of these technologies or on their isolated implementation, while the optimal strategy for incorporating molecular results into real-world antimicrobial decision-making remains unclear.
A major unanswered question is not whether multiplex molecular diagnostics can identify microorganisms faster, but how these results should be integrated with clinical and laboratory information to guide antimicrobial prescribing decisions. Current evidence suggests that rapid molecular diagnostics alone may be insufficient to improve outcomes unless they are incorporated into structured antimicrobial stewardship interventions.
The present study addresses this knowledge gap by evaluating an innovative antimicrobial stewardship strategy that combines real-time multiplex molecular microbiology results with predefined clinical and laboratory criteria within an established multidisciplinary ASP. Rather than assessing a diagnostic test in isolation, this study evaluates a standardized decision-making framework designed to translate rapid microbiological information into actionable antimicrobial recommendations.
This is an open-label, pragmatic, cluster-randomized crossover clinical trial conducted at Hospital General Universitario de Elche. Hospital units constitute the clusters and are grouped according to the type of care provided. Clusters are randomized to either the intervention strategy or the standard antimicrobial stewardship strategy during an initial study period.
All eligible patients admitted to a given unit during each study period receive the stewardship strategy assigned to that unit. Individual patients are not randomized.
After completion of the first intervention period, a washout period is implemented to minimize potential carry-over effects. Subsequently, the clusters cross over and receive the alternative stewardship strategy for a second study period. This design allows each participating unit to act as its own control while reducing the impact of differences in patient populations and clinical practice patterns between units.
Eligible participants are hospitalized adults receiving empiric high-impact antimicrobial therapy under ASP supervision. The intervention evaluates whether integrating molecular microbiology into a structured stewardship algorithm enables earlier and more appropriate antimicrobial optimization than conventional stewardship practice.
The primary objective is to determine whether this strategy reduces exposure to high-impact antimicrobial therapy. Secondary objectives include evaluating antimicrobial appropriateness, infection-related outcomes, intensive care unit admission, hospital readmission, recurrence of infection, mortality, adverse events related to antimicrobial therapy, and healthcare costs.
By focusing on the implementation of a standardized stewardship strategy rather than on the diagnostic technology itself, this study seeks to generate clinically relevant evidence regarding how rapid molecular microbiology can be effectively incorporated into routine antimicrobial stewardship programs. The results may contribute to the development of more effective and reproducible antimicrobial optimization strategies and help define the role of molecular diagnostics in everyday clinical practice.
Eligibility
Inclusion Criteria:
- Age ≥18 years
- Hospitalized in one of the participating study units at Hospital General Universitario de Elche.
- Initiation of empiric high-impact antimicrobial therapy subject to antimicrobial stewardship program (ASP) review.
- Provision of written informed consent by the participant or, when applicable, by a legally authorized representative.
Exclusion Criteria:
- Severe immunosuppression with profound neutropenia (\<100 neutrophils/mm³).
- Previous enrollment in this clinical trial.
- Expected survival of less than 48 hours.
- Documented microbiological identification of the presumed causative pathogen by conventional methods in a representative and/or sterile sample before randomization and before availability of multiplex molecular microbiology results.
