Impact of BioFire FilmArray Pneumonia Panel vs Routine Diagnostics on Antimicrobial Outcomes (DOOR-MAT)

• Multiplex PCR-based pneumonia panel (BIOFIRE® FILMARRAY® Pneumonia Panel) (Diagnostic test): The BIOFIRE® FILMARRAY® Pneumonia Panel is a rapid, automated molecular diagnostic test designed to detect a broad range of respiratory pathogens directly from lower respiratory tract samples, such as sputum, tracheal aspirates, or bronchoalveolar lavage. The system integrates sample preparation, nucleic acid extraction, amplification, and detection into a single, fully automated platform. The test can identify multiple bacterial and viral pathogens, as well as key antimicrobial resistance genes, within approximately one hour. It provides semi-quantitative results for selected bacteria, which may help differentiate colonization from infection. The panel is designed for ease of use and requires minimal hands-on time. By delivering rapid and comprehensive microbiological results, the BIOFIRE® FILMARRAY® Pneumonia Panel has the potential to support earlier optimization of antimicrobial therapy, improve clinical decision-making, and contribute to antimicrobial stewardship efforts, partic

Primary outcomes

• Adequacy of antimicrobial prescriptions using the Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR-MAT). [24 hours after the sample receipt in the microbiology laboratory]: Adequacy of antimicrobial prescriptions using the following scoring system based on DOOR-MAT analysis within the first 24 hours after the sample receipt. Antimicrobial therapy will be evaluated on the first day after inclusion and classified by two blinded infectious disease physicians according to the criteria described below. In case of disagreement, a third evaluator will adjudicate using the same criteria. : * Ideal treatment (most desirable): Preferred antibiotic, without unnecessary additional antimicrobials. 100 points. * Overtreatment: Preferred antibiotic + combination with unnecessary antimicrobials or active antimicrobials with a broader spectrum than necessary. 50 points. * Inactive or suboptimal treatment* (least desirable). 0 points. Patients with no diagnosis (negative culture and Biofire negative)-0 points. *Patients receiving active drugs in vitro, but not preferred in clinical practice.

Secondary outcomes

• Proportion of days in under-treatment and/or overtreatment [7 days]: Proportion of days in under-treatment and/or overtreatment during the first 7 days (D1-D7) after study inclusion and time to ideal therapy in both groups. DOOR - Response Adjusted for Duration of Antibiotic Risk (RADAR).
• Simulated ideal Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR-MAT) scores [24 hours]: Antimicrobial prescription convenience scores on the first day, simulating these choices made by physicians following the BIOFIRE® FILMARRAY panels' results (ideal scores): - Ideal treatment (most desirable): Preferred antibiotic, without unnecessary additional antimicrobials. 100 points. - Overtreatment: Preferred antibiotic + combination with unnecessary antimicrobials or active antimicrobials with a broader spectrum than necessary. 50 points. - Inactive or suboptimal treatment* (least desirable). 0 points. Patients with no diagnosis (negative culture and Biofire negative)-0 points.
• Agreement between real Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR-MAT) scores and ideal scores [24 hours]: Agreement between real desirability DOOR-MAT scores and ideal scores considering the rapid test results were followed (this is only within the intervention arm): - Ideal treatment (most desirable): Preferred antibiotic, without unnecessary additional antimicrobials. 100 points. - Overtreatment: Preferred antibiotic + combination with unnecessary antimicrobials or active antimicrobials with a broader spectrum than necessary. 50 points. - Inactive or suboptimal treatment* (least desirable). 0 points. Patients with no diagnosis (negative culture and Biofire negative)-0 points.
• 30-day mortality [30 days]: Comparison of 30-day mortality rates between the intervention and control arms.
• Clinical outcomes from Desirability of Outcome Ranking (DOOR) [2, 7 and 14 days]: Clinical outcomes will be assessed using the DOOR at days 2, 7, and 14. Patients will be assigned a score from 1 (most desirable outcome) to 5 (least desirable outcome) based on the occurrence of the following events: (1) absence of clinical response, (2) infectious complications, and (3) serious adverse events. Patients who do not develop any of these events will be assigned a score of 1; those who develop one, two, or all three events will be assigned scores of 2, 3, and 4, respectively. Patients who die will be assigned a score of 5.
• Agreement between Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR-MAT) and Clinical DOOR scores [14 days]: Agreement between DOOR-MAT scores at 24 hours (desirability scale ranging from 0 \[least desirable\] to 100 \[most desirable\]) and clinical outcome scores at 14 days (ordinal scale ranging from 1 \[most desirable\] to 5 \[least desirable\]) will be evaluated in a two-dimensional space.
• Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR-MAT) scores in subgroups [24 hours]: DOOR-MAT scores in subgroups with microbiologically confirmed infections, viral infections, gram-positive infections, gram-negative infections, and carbapenem-resistant gram-negative infections: - Ideal treatment (most desirable): Preferred antibiotic, without unnecessary additional antimicrobials. 100 points. - Overtreatment: Preferred antibiotic + combination with unnecessary antimicrobials or active antimicrobials with a broader spectrum than necessary. 50 points. - Inactive or suboptimal treatment* (least desirable). 0 points. Patients with no diagnosis (negative culture and Biofire negative)-0 points. *Patients receiving active drugs in vitro, but not preferred in clinical practice.
• Cost-effectiveness analysis [through study completion, an average of 1 year]: To compare cost-effectiveness between the BioFire arm and the control arm using retrospectively collected data from the hospital management system.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age ≥18 years.
* Clinical diagnosis of hospital-acquired pneumonia or clinically relevant tracheobronchitis requiring antimicrobial treatment, with or without mechanical ventilation.
* No respiratory cultures collected in the last 72 hours (except for the culture that will potentially be evaluated in the study-trigger for inclusion).
* Agreement from the patient or legal representative to sign the Informed Consent Form (ICF).

Exclusion Criteria:

* Inadequate respiratory samples according to laboratory cutoffs for squamous epithelial cells and polymorphonuclear leukocytes (sputum or endotracheal aspirate).
* Incarcerated populations.
* Pregnant women.

• Evans SR, Rubin D, Follmann D, Pennello G, Huskins WC, Powers JH, Schoenfeld D, Chuang-Stein C, Cosgrove SE, Fowler VG Jr, Lautenbach E, Chambers HF. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015 Sep 1;61(5):800-6. doi: 10.1093/cid/civ495. Epub 2015 Jun 25. PMID 26113652
• Wilson BM, Jiang Y, Jump RLP, Viau RA, Perez F, Bonomo RA, Evans SR. Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR MAT): A Framework for Assessing Antibiotic Selection Strategies in the Presence of Drug Resistance. Clin Infect Dis. 2021 Jul 15;73(2):344-350. doi: 10.1093/cid/ciaa1769. PMID 33245333
• Howard-Anderson J, Hamasaki T, Dai W, Collyar D, Rubin D, Nambiar S, Kinamon T, Leister-Tebbe H, Hill C, Geres H, Holland TL, Doernberg SB, Chambers HF, Fowler VG Jr, Evans SR, Boucher HW; Antibacterial Resistance Leadership Group. Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia. Clin Infect Dis. 2024 Feb 17;78(2):259-268. doi: 10.1093/cid/ciad576. PMID 37740559

• Maria Helena Rigatto, MD, PhD, Principal investigator, Hospital de Clinicas de Porto Alegre