Molecular Microbiology- Guided Antimicrobial Stewardship Versus Standard Stewardship in Hospitalized Patients

Official title

Impact of Molecular Microbiology Integrated With Clinical Data on Antimicrobial Therapy Optimization: An Open-Label Cluster-Randomized Crossover Trial

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.

Detailed 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.

Interventions

• Behavioral Protocolized Antimicrobial Stewardship Strategy
  A standardized antimicrobial stewardship strategy integrating multiplex molecular microbiology results with predefined clinical and laboratory criteria to support antimicrobial prescribing decisions.
• Behavioral Standard Antimicrobial Stewardship
  Routine antimicrobial stewardship practice based on standard clinical assessment and conventional microbiological information.

Primary outcome measures

• Duration of Exposure to High-Impact Antimicrobial Therapy [Time frame: Up to 30 days after initiation of high-impact antimicrobial therapy]

Secondary outcome measures (9)

• Infection-Related Mortality [Time frame: 30 days]
• Antimicrobial-Related Adverse Events [Time frame: Up to 30 days after randomization]
• Appropriate Antimicrobial Therapy at 24 Hours [Time frame: 24 hours after randomization]
• Appropriate Antimicrobial Therapy at 72 Hours [Time frame: 72 hours after randomization]
• Intensive Care Unit Admission [Time frame: Up to 30 days after randomization]
• Hospital Readmission [Time frame: Within 10 days after hospital discharge]
• Recurrence of Infection [Time frame: 30 days]
• Healthcare Costs [Time frame: Up to 5 days after discharge]
• Infection-Related Complications [Time frame: Up to 30 days after randomization]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Health services research

Study locations

Spain · 1 center

• Hospital General Universitario de Elche — Elche

Publications

• Holma T, Torvikoski J, Friberg N, Nevalainen A, Tarkka E, Antikainen J, Martelin JJ. Rapid molecular detection of pathogenic microorganisms and antimicrobial resistance markers in blood cultures: evaluation and utility of the next-generation FilmArray Blood Culture Identification 2 panel. Eur J Clin Microbiol Infect Dis. 2022 Mar;41(3):363-371. doi: 10.1007/s10096-021-04314-2. Epub 2021 Aug 5. PMID 34350523
• Murphy CN, Fowler R, Balada-Llasat JM, Carroll A, Stone H, Akerele O, Buchan B, Windham S, Hopp A, Ronen S, Relich RF, Buckner R, Warren DA, Humphries R, Campeau S, Huse H, Chandrasekaran S, Leber A, Everhart K, Harrington A, Kwong C, Bonwit A, Dien Bard J, Naccache S, Zimmerman C, Jones B, Rindlisbacher C, Buccambuso M, Clark A, Rogatcheva M, Graue C, Bourzac KM. Multicenter Evaluation of the Bio PMID 32350043
• Moy AC, Kimmoun A, Merkling T, Bercot B, Camelena F, Poncin T, Deniau B, Mebazaa A, Dudoignon E, Depret F; PCR Multiplex Study group (PMS group). Performance evaluation of a PCR panel (FilmArray(R) Pneumonia Plus) for detection of respiratory bacterial pathogens in respiratory specimens: A systematic review and meta-analysis. Anaesth Crit Care Pain Med. 2023 Dec;42(6):101300. doi: 10.1016/j.accpm. PMID 37709201
• Horcajada JP, Grau S, Pano-Pardo JR, Lopez A, Oliver A, Cisneros JM, Rodriguez-Bano J. Antimicrobial stewardship in Spain: Programs for Optimizing the use of Antibiotics (PROA) in Spanish hospitals. Germs. 2018 Sep 3;8(3):109-112. doi: 10.18683/germs.2018.1137. eCollection 2018 Sep. No abstract available. PMID 30250829
• Peri AM, Chatfield MD, Ling W, Furuya-Kanamori L, Harris PNA, Paterson DL. Rapid Diagnostic Tests and Antimicrobial Stewardship Programs for the Management of Bloodstream Infection: What Is Their Relative Contribution to Improving Clinical Outcomes? A Systematic Review and Network Meta-analysis. Clin Infect Dis. 2024 Aug 16;79(2):502-515. doi: 10.1093/cid/ciae234. PMID 38676943
• Enne VI, Stirling S, Barber JA, High J, Russell C, Brealey D, Dhesi Z, Colles A, Singh S, Parker R, Peters M, Cherian BP, Riley P, Dryden M, Simpson R, Patel N, Cassidy J, Martin D, Welters ID, Page V, Kandil H, Tudtud E, Turner D, Horne R, O'Grady J, Swart AM, Livermore DM, Gant V; INHALE WP3 Study Group and Committees. INHALE WP3, a multicentre, open-label, pragmatic randomised controlled trial PMID 39961847

Identifiers

NCT: NCT07684300 · 2026.002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗