Potentially Erroneous Antimicrobial Susceptibility Testing Results when Tobramycin Minimum Inhibitory Concentration was 2 mg/L and the Implications for Pediatricians
Eugene Y H YeungAbstract
Background
Biomerieux VITEK2 system is a fast, automated instrument for microbial identification and antibiotic susceptibility testing (AST) and commonly used in clinical laboratories. However, Clinical & Laboratory Standards Institute (CLSI) recommends verification of commercial AST with selected microorganism-antimicrobial combinations prior to diagnostic use in clinical laboratories. Tobramycin is an aminoglycoside antimicrobial which is generally effective against Enterobacterales and commonly used for infections in pediatrics. Our clinical laboratory incidentally found a Enterobacterales clinical isolate with tobramycin susceptible result (minimum inhibitory concentration or MIC = 2 mg/L) on VITEK2 (with AST-N391 card) but intermediate result on traditional Etest, indicating a minor error. In both the EUCAST and CLSI 2024 guidance, MIC <=2 would indicate susceptible. We subsequently carried out an ad-hoc verification study in hope of reassuring the validity of tobramycin AST results on VITEK2.
Methods
The current study was conducted in LifeLabs microbiology regional laboratories, connected with 129 collection centers in urban and rural communities in in British Columbia, Canada. Thirty consecutive Enterobacterales clinical isolates with MIC of 2 mg/L on VITEK2 were selected to undergo AST by traditional Etest, using the recommended methods in CLSI M100 (2024) and M52 (2015). The MIC breakpoints used were as per CLSI (2024): susceptible <=2 mg/L; intermediate = 4 mg/L; resistant => 8 mg/L.
Results
Despite achieving MIC of 2 mg/L on VITEK2, 16 and 3 of the isolates showed intermediate (MIC = 4 mg/L) and resistant (MIC => 8 mg/L) AST results with tobramycin Etest. respectively, equivalent to 53.3% minor error and 27.3% major error rates.
Conclusions
Our laboratory decided not to automatically release VITEK2 tobramycin AST results for Enterobacterales and will perform Etest when tobramycin AST is requested. Other microbiology laboratories are encouraged to perform their internal verification study to confirm the validity of tobramycin AST results on VITEK2. Pediatricians should be cautious when they encounter tobramycin MIC of 2 mg/L from the automated VITEK2 system.