Evaluation of two rapid molecular test systems to establish an algorithm for fast identification of bacterial pathogens from positive blood cultures

Abstract

Fast identification of pathogens directly from positive blood cultures is of highest importance to supply an adequate therapy of bloodstream infections (BSI). There are several platforms providing molecular-based identification, detection of antimicrobial resistance genes, or even a full antimicrobial susceptibility testing (AST). Two of such test systems allowing rapid diagnostics were assessed in this study: The Biofire FilmArray® and the Genmark ePlex®, both fully automated test system with a minimum of hands-on time. Overall 137 BSI episodes were included in our study and compared to conventional culture–based reference methods. The FilmArray® is using one catridge including a panel for the most common bacterial and fungal BSI pathogens as well as selected resistance markers. The ePlex® offers three different cartridges for detection of Gram-positives, Gram-negatives, and fungi resulting in a broader panel including also rare pathogens, putative contaminants, and more genetic resistance markers. The FilmArray® and ePlex® were evaluated for all 137 BSI episodes with FilmArray® detecting 119 and ePlex® detecting 128 of these. For targets on the respective panel of the system, the FilmArray® generated a sensitivity of 98.9% with 100% specificity on Gram-positive isolates. The ePlex® system generated a sensitivity of 94.7% and a specificity of 90.7% on Gram-positive isolates. In each case, the two systems performed with 100% sensitivity and specificity for the detection of Gram-negative specimens covered by each panel. In summary, both evaluated test systems showed a satisfying overall performance for fast pathogen identification and are beneficial tools for accelerating blood culture diagnostics of sepsis patients.

Evaluation of Microbiological Performance and the Potential Clinical Impact of the ePlex® Blood Culture Identification Panels for the Rapid Diagnosis of Bacteremia and Fungemia

“…Identification to the species level was obtained for 61% of GP bacteria, 90% of GN bacteria, and 87.5% of fungi. Identification to the genus level increased detection rate of GN pathogens to 93%, while 87 and 88% had been previously detected in other studies analyzing 125 and 33 positive blood cultures respectively (Huang et al, 2019;Oberhettinger et al, 2020). Identification to the genus level increased identification rate to 91% for the GP strains, mainly because putative contaminants such as Coagulase-negative Staphylococcus species, Corynebacterium and Micrococcus strains are only identified to the genus level, with the exception of S. epidermidis and S. lugdunensis species identified by the BCID-GP Panel.…”

“…Gram stain is required prior to performing the test to choose the appropriate ePlex BCID Panel(s) and prevents the user from running the test on false-positive blood cultures. The list of targets present on the panels seems well designed, as only 9% of GP bacteria, 5% of GN bacteria, and 13% of fungi were not included on the panels in our study, while previous reports found between 2.2% (for the BCID-GP Panel only) and 6% of pathogens untargeted by the panels (Maubon et al, 2018;Huang et al, 2019;Carroll et al, 2020;Oberhettinger et al, 2020). Identification to the species level was obtained for 61% of GP bacteria, 90% of GN bacteria, and 87.5% of fungi.…”

“…Identification to the genus level increased identification rate to 91% for the GP strains, mainly because putative contaminants such as Coagulase-negative Staphylococcus species, Corynebacterium and Micrococcus strains are only identified to the genus level, with the exception of S. epidermidis and S. lugdunensis species identified by the BCID-GP Panel. Three recent evaluations of 98, 94, and 1,297 positive blood cultures with GP bacteria, respectively, also accurately identified 91% of the strains to the species or genus level (Huang et al, 2019;Carroll et al, 2020;Oberhettinger et al, 2020). Importantly, the ePlex BCID-GP Panel permitted the distinction between E. faecalis and E. faecium species for 14 strains, allowing an earlier switch toward beta-lactam antibiotics if E. faecalis was identified (i.e.…”

“…As only a limited number of genera or species represent over 80% of BSI, molecular methods have been developed and implemented in several laboratories. Large syndromic multiplex PCR panels such as the ePlex BCID Panels are now able to provide identification and detection of clinically relevant pathogens and antimicrobial resistance genes in one to two hours (Altun et al, 2013;Banerjee et al, 2016;Fiori et al, 2016;Kim et al, 2016;Timbrook et al, 2017;Beckman et al, 2019;Huang et al, 2019;Oberhettinger et al, 2020). Gram stain is required prior to performing the test to choose the appropriate ePlex BCID Panel(s) and prevents the user from running the test on false-positive blood cultures.…”

“…The ePlex BCID-GP Panel also identifies GP rods belonging to the genera Corynebacterium, Lactobacillus, Bacillus (B. subtilis group and B. cereus group) and the anaerobic species Cutibacterium acnes, authorizing faster deescalation of antibiotic therapy if a contaminant is identified. Recent comparison of the FilmArray ® and ePlex BCID Panel performances on 98 GP bacterial samples respectively showed 29 versus 68% identification of GP bacteria to the species level and 88 versus 91% identification to the genus level (Oberhettinger et al, 2020).…”