Susceptibility Testing by Volatile Organic Compound Detection Direct from Positive Blood Cultures: A Proof-of-Principle Laboratory Study

Background: Bacteria produce volatile organic compounds (VOCs) during growth, which can be detected by colorimetric sensor arrays (CSAs). The SpecifAST (R) system (Specific Diagnostics) employs this technique to enable antibiotic susceptibility testing (AST) directly from blood cultures without prior subculture of isolates. The aim of this study was to compare the SpecifAST (R) AST results and analysis time to the VITEK (R) 2 (bioMerieux) system. Methods: In a 12-month single site prospective study, remnants of clinical positive monomicrobial blood cultures were combined with a series of antibiotic concentrations. Volatile emission was monitored at 37 degrees C via CSAs. Minimal Inhibitory Concentrations (MICs) of seven antimicrobial agents for Enterobacterales, Staphylococcus, and Enterococcus spp. were compared to VITEK (R) 2 AST results. MICs were interpreted according to EUCAST clinical breakpoints. Performance was assessed by calculating agreement and discrepancy rates. Results: In total, 96 positive blood cultures containing Enterobacterales, Staphylococcus, and Enterococcus spp. were tested (269 bug-drug combinations). The categorical agreement of the SpecifAST (R) system compared to the VITEK (R) 2 system was 100% and 91% for Gram-negatives and Gram-positives, respectively. Errors among Gram-positives were from coagulase-negative staphylococci. Overall results were available in 3.1 h (+/- 0.9 h) after growth detection without the need for subculture steps. Conclusion: The AST results based on VOC detection are promising and warrant further evaluation in studies with a larger sample of bacterial species and antimicrobials.

Automated summary

Bacteria produce VOCs during growth, which can be detected by CSAs. The SpecifAST (R) system enables AST directly from blood cultures, with results available within 3.1 hours of growth detection without subculture steps. In a 12-month study, the system showed 100% and 91% categorical agreement with VITEK (R) 2 for Gram-negatives and Gram-positives, respectively. Further evaluation with a larger sample of bacterial species and antimicrobials is needed.