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A2617 - Clinical Evaluation and Potential Impact of a Semi-Quantitative Multiplex Molecular Assay for the Identification of Pathogenic Bacteria and Viruses in Lower Respiratory Specimens
Author Block: B. Buchan1, S. Windham1, M. Faron1, J. Balada-Llasat2, R. Relich3, R. Humphries4, S. Miller4, A. Harrington5, C. Murphy6, A. Leber7, J. Dien Bard8, C. Zimmerman9, S. Kerr10, C. Graue10, N. Ledeboer1, A. Huang11; 1Pathology, The Medical College of Wisconsin, Milwaukee, WI, United States, 2Pathology, The Ohio State University, Columbus, OH, United States, 3Pathology, Indiana University, Indianapoilis, IN, United States, 4Pathology, The University of California - Los Angeles, Los Angeles, CA, United States, 5Pathology, Loyola University Medical Center, Maywood, IL, United States, 6Pathology, University of Nebraska Medical Center, Omaha, NE, United States, 7Pathology, Nationwide Childrens Hospital, Columbus, OH, United States, 8Pathology, Childrens Hospital of Los Angeles, Los Angeles, CA, United States, 9MRI Global, Palm Bay, FL, United States, 10BioFire Diagnostics, Salt Lake City, UT, United States, 11Pharmacy, Froedtert Hospital, Milwaukee, WI, United States.
Rationale: Rapid identification of organisms causing lower respiratory tract infections is central to appropriate antimicrobial utilization; however, culture methods are slow and insensitive, and molecular tests are not available or are not routinely ordered. We evaluated the FilmArray Pneumonia Panel (FA-Pneumo) (BioFire Diagnostics, Salt Lake City, UT) for detection of respiratory pathogens in bronchoalveolar lavage (BAL) specimens.
Methods: BAL (n=259) were collected from inpatients with symptoms of respiratory tract infection at 8 US hospitals. Specimens were tested using an Investigational Use Only (IUO) version of the FA-Pneumo, which identifies 17 bacterial agents (14 reported semi-quantitatively) in addition to 9 viral agents. FA-Pneumo results were compared to standard of care (SOC) methods including culture and PCR based on clinician order. Chart review was conducted to determine type and duration of antibiotic (abx) therapy for each subject.
Results: The FA-Pneumo demonstrated a positive percent agreement of 96.2% (84/87) and a negative percent agreement of 97.6% (3464/3548) for bacterial targets in BAL specimens. The three “false-negative” results included P. aeruginosa reported as “few” and 3log10 cfu/mL, and S. aureus reported as 3log10 cfu/mL by SOC culture. Among 84 “false-positive” results, 50% occurred in patients that received effective abx within 72 h prior to specimen collection. An additional 42% of specimens “false-positive” results contained significant normal oral flora that potentially obscured the pathogen. Multiple bacterial targets were identified by the FA-Pneumo in 32 specimens; in 28/32 (88%) the bacterium identified as predominant matched the predominant organism identified by SOC culture. The FA-Pneumo identified a viral pathogen in 48/259 (18.5%) specimens. A SOC test capable of detecting the identified viral agent was ordered in only 11/48 (22%) of specimens. Results from the FA-Pneumo could have been used to alter abx prescription in 175/243 (68%) of evaluable patients. This included de-escalation of at least one antibiotic for 122/175 (70%) patients totaling a combined 18,284 antibiotic hours. Antibiotics were escalated in 5/175 (3%) patients who were not covered by empirical therapy.
Conclusions: The FA-Pneumo demonstrated high PPA compared to culture and identified potential pathogens in ~70% more specimens than SOC. Use of a comprehensive molecular panel may aid in the identification of potential pathogens in complex specimens or after the initiation of antibiotics resulting in earlier identification of respiratory pathogens and optimization of antibiotic therapy. Data presented were generated using assays that have not been reviewed by regulatory agencies for in vitro diagnostic use.