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The purpose of this study was to assess the clinical impact of the BioFire FilmArray Meningitis/Encephalitis (ME) panel on antimicrobial use and clinical outcomes. This retrospective, quasi-experiment evaluated adult and pediatric patients with suspected ME, evidenced by cerebrospinal fluid (CSF) culture. Hospital-acquired meningitis patients and patients who received antimicrobials >48 h prior to lumbar puncture were excluded. The primary endpoint was days of antimicrobial therapy pre- and post-implementation of the ME panel. Secondary endpoints included total length of stay, 30-day readmission, and individual days of antimicrobial therapy. Two hundred and sixty-four total adult and pediatric patients were included. Antimicrobial days of therapy had a median of 3 days (IQR 0–5) in the pre vs. post group with a median of 2 days (2–5) (<i>p</i> = 0.099). Days of therapy for acyclovir were significantly decreased in the post group (median 2 days [IQR 1–3] vs. 3 days [IQR 2.5–4.5], <i>p</i> = 0.0002). There were no significant differences in the secondary endpoints. Overall, implementation of the ME panel impacted the duration of antimicrobials, particularly acyclovir; however, opportunities for further education regarding antimicrobial de-escalation and utilization of the panel were identified. Antimicrobial stewardship program intervention is critical to maximize benefit of this rapid diagnostic test.