Reviewed by Dr. Michael Payne, MD, London Health Sciences Centre
Rapid pathogen identification and antimicrobial susceptibility testing (AST) from patients with blood stream infections (BSI) can improve patient management and assist with antimicrobial stewardship interventions. Two recent studies evaluated rapid BSI diagnostics. Both studies found the rapid diagnostic methods to be accurate and provide results before standard identification and AST would be routinely available. Molecular diagnostic platforms provide the most rapid ID/AST results but may be limited where resistance mechanisms are complex/multiple genetic markers (eg third-generation cephalosporin resistance in Enterobacterales). Rapid phenotypic AST utilizing direct disk diffusion (dDD), is accurate, cost effective, and although less rapid than molecular methods, is able to detect resistance independent of genetic mechanism.
The first study utilized a commercial molecular platform to provide pathogen identification and detect genotypic resistance markers. The Biofire FilmArray BCID2 panel, is an update to the original BCID panel, identifying 33 species and 10 genetic resistance markers, including common carbapenemase encoding genes (i.e. blaKPC, blaIMP, blaNDM, blaOXA-48-like, blaVIM), the most common ESBL-gene (blaCTX-M) along with mecA, vanA/B and mcr-1. The study evaluated the BCID2 assay performance for species identification in 180 positive blood cultures. BCID2 results were concordant with standard identification in 159/180 (88.3%) blood cultures. Identification was concordant for 68/74 (91.9%) and 71/74 (96.0%) of all samples growing mono-bacterial, Gram-positive or Gram-negative pathogens, respectively. Non-concordance was related to the detection of additional pathogens by the BCID2 (n= 4), discrepant species identification (n= 4), or failure of BCID2 to detect on-panel pathogens (n= 1). A number (12/31; 38.7%) of discordant results were detected in poly-microbial specimens. BCID2 identified presence of blaCTX-M carrying species in 12 specimens but failed to predict a third-generation cephalosporin resistance in four isolates exhibiting independent cephalosporin-resistance mechanisms. Carbapenem-resistance related to the presence of bla VIM-2 or bla Oxa-48-like was correctly predicted in two isolates. The BCID2 assay is a rapid and accurate platform for species identification and resistance genetic marker identification. However, due to the multifactorial mechanism of β-lactam resistance in Gram-negative organisms, consideration should be given to combining BCID2 results with rapid phenotypic AST in order to inform antimicrobial stewardship interventions.
The second study utilized standard MALDI-TOF for identification, as well as dDD from positive blood culture broth for rapid AST. The retrospective cohort study included 582 blood cultures from 495 pediatric patients with bacteremia. They evaluated the Antibiotic Spectrum Index of prescribed antibiotics to assess change in antibiotic prescribing after availability of Gram stain, dDD, and AST results. dDD results were available a median of 21 h before AST results. dDD had positive predictive values of 96% for most organism-antibiotic pairs, including 100% (CI 96 to 100%) for Staphylococcus aureus with oxacillin and 99% (CI 93 to 100%) for Enterobacterales with ceftriaxone. Very major errors and major errors occurred in 31/5,454 (0.6%) and 231/5,454 (4.2%) organism-antibiotic combinations, respectively. Antibiotics therapy was narrowed in 30% of cases after dDD results and a further 25% of cases after standard AST results. dDD is a rapid, cost effective and accurate method to predict pathogen susceptibility, allowing for potential narrowing of antibiotic therapy one day earlier than with standard AST reporting.