Prediction of Infectious Agents in the Biofire® FilmArray bioMérieux Meningitis/Encephalitis Panel Based on Clinical Syndrome and Cerebrospinal Fluid Parameters: a Diagnostic Stewardship Proposal.

Overview

Background: Infections of the central nervous system (CNS) are associated with high morbidity, mortality, and high resource consumption. The BioFire FilmArray is a molecular diagnostic panel capable of identifying 14 pathogens in approximately one hour, including bacteria, viruses, and fungi. However, it is not yet widely available in the Brazilian public health system. Objective: The primary objective of this study is to evaluate the pre-test probability of positivity of the Biofire FilmArray bioMérieux Meningitis/Encephalitis panel in patients with clinical syndrome of meningitis and/or encephalitis and pleocytosis (CSF ≥ 5 cells). As secondary objectives, the study aims to: Determine the clinical impact of using the panel through variables such as total hospital stay and length of stay in the intensive care unit. Compare the duration of antibiotic use in non-bacterial cases between groups. Compare the time to reduction of acyclovir use in etiologies without proven benefit. Compare the time for identification of the causative pathogen and mortality rates between the study groups. Perform a cost-effectiveness analysis of the test. Compare the request for imaging exams, such as brain MRI and CT scan, between the groups. Methods: This is a prospective, transversal, and multicenter study conducted at Santa Casa de Porto Alegre and Hospital Dom João Becker. Patients will be compared with a retrospective cohort used as a control group.

Detailed description

This will be a prospective study, conducted at Santa Casa de Porto Alegre, a philanthropic tertiary university hospital with 1,400 beds and at Hospital Dom João Becker, which has 173 inpatient beds and 20 ICU beds. Adult patients with clinical symptoms compatible with CNS infection that began less than 30 days prior, for whom cerebrospinal fluid collection has been indicated by the attending physician, will be included. Participation in the study will be subject to the signing of an informed consent form (ICF) by the patient or their legal representative. The patient will then be included in the study. Samples will be processed with qualitative and quantitative cytology, protein, glucose, and lactate analysis, as well as specific tests as requested by the attending physician. Patients will be compared with a retrospective cohort used as a control group (patients with clinical CNS infection who underwent cerebrospinal fluid collection but were not tested with the FilmArray panel) over the past 4 years.

Interventions

• Diagnostic test Biofire FilmArray Meningitis/Encephalitis Panel
  The Biofire FilmArray is a multiplex molecular diagnostic test that will be performed on 0.2 mL of cerebrospinal fluid (CSF) collected from patients via lumbar or suboccipital puncture. The system automatically performs DNA/RNA extraction, purification, multiplex PCR, and identification of 14 different pathogens (6 bacteria, 7 viruses, and 1 fungus). The complete process takes approximately one hour and provides qualitative results to guide therapeutic decisions such as antibiotic stewardship.

Primary outcome measures

• Rate of BioFire® FilmArray® Meningitis/Encephalitis Panel Positivity [Time frame: At the time of BioFire® FilmArray® result availability, assessed up to 24 months]

Secondary outcome measures (9)

• Total hospital length of stay in days [Time frame: From hospital admission until hospital discharge or death, whichever occurs first, assessed up to 24 months.]
• Intensive care unit length of stay in days [Time frame: From intensive care unit admission until intensive care unit discharge or death, whichever occurs first, assessed up to 24 months.]
• Duration of antibiotic therapy in participants without confirmed bacterial infection [Time frame: From antibiotic initiation until discontinuation, hospital discharge, or death, whichever occurs first, assessed up to 24 months.]
• Duration of acyclovir therapy in participants without confirmed indication [Time frame: From acyclovir initiation until discontinuation, hospital discharge, or death, whichever occurs first, assessed up to 24 months.]
• Time to pathogen identification [Time frame: From cerebrospinal fluid collection until pathogen identification, when available, assessed up to 24 months.]
• In-hospital mortality [Time frame: From hospital admission until death or hospital discharge, whichever occurs first, assessed up to 24 months.]
• Need for hemodialysis [Time frame: From hospital admission until hospital discharge or death, whichever occurs first, assessed up to 24 months.]
• Direct medical costs [Time frame: From hospital admission until hospital discharge or death, whichever occurs first, assessed up to 24 months.]
• Use of neuroimaging [Time frame: From hospital admission until hospital discharge or death, whichever occurs first, assessed up to 24 months.]

Eligibility criteria

Inclusion criteria

Patients aged 18 years or older, of any gender.

Presence of at least two of the following symptoms: fever, lethargy, altered level of consciousness, seizures, acute focal deficit, signs of meningeal irritation, or headache.

Symptoms must have started within the last 30 days.

Obligatory presence of pleocytosis (CSF white blood cell count ≥ 5 cells/mm³).

Provision of written Informed Consent (TCLE) by the patient or their legal representative.

Exclusion criteria

• Failure to sign the Informed Consent Form.

Clinical manifestations lasting more than 30 days.

Patients under 18 years of age.

Patients who have undergone neurosurgery within 30 days prior to the onset of symptoms (applies to both prospective and control groups).

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Brazil · 1 center

• Irmandande Santa Casa de Porto Alegre — Porto Alegre

Publications

• Cailleaux M, Pilmis B, Mizrahi A, Lourtet-Hascoet J, Nguyen Van JC, Alix L, Couzigou C, Vidal B, Tattevin P, Le Monnier A. Impact of a multiplex PCR assay (FilmArray(R)) on the management of patients with suspected central nervous system infections. Eur J Clin Microbiol Infect Dis. 2020 Feb;39(2):293-297. doi: 10.1007/s10096-019-03724-7. Epub 2019 Nov 12. PMID 31720944
• Duff S, Hasbun R, Balada-Llasat JM, Zimmer L, Bozzette SA, Ginocchio CC. Economic analysis of rapid multiplex polymerase chain reaction testing for meningitis/encephalitis in adult patients. Infection. 2019 Dec;47(6):945-953. doi: 10.1007/s15010-019-01320-7. Epub 2019 May 20. PMID 31111325
• Soucek DK, Dumkow LE, VanLangen KM, Jameson AP. Cost Justification of the BioFire FilmArray Meningitis/Encephalitis Panel Versus Standard of Care for Diagnosing Meningitis in a Community Hospital. J Pharm Pract. 2019 Feb;32(1):36-40. doi: 10.1177/0897190017737697. Epub 2017 Nov 1. PMID 29092659
• Trujillo-Gomez J, Tsokani S, Arango-Ferreira C, Atehortua-Munoz S, Jimenez-Villegas MJ, Serrano-Tabares C, Veroniki AA, Florez ID. Biofire FilmArray Meningitis/Encephalitis panel for the aetiological diagnosis of central nervous system infections: A systematic review and diagnostic test accuracy meta-analysis. EClinicalMedicine. 2022 Feb 14;44:101275. doi: 10.1016/j.eclinm.2022.101275. eCollection PMID 35198914

Identifiers

NCT: NCT07432113 · 88825625.5.0000.5335 · U1111-1334-6700

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗