Abstract
We prospectively evaluated EUCAST rapid antimicrobial susceptibility testing methodology for susceptibility testing directly from blood culture bottles in comparison to CLSI disk-diffusion method. During May-November 2019, positively flagged blood culture bottles showing Gram-negative micro-organisms were simultaneously processed by rapid antimicrobial susceptibility testing and CLSI methodology. Antibiotics tested were cefotaxime, ceftazidime, piperacillin-tazobactam, imipenem, meropenem, gentamicin, tobramycin and trimethoprim-sulphamethoxazole. Overall, 80 isolates identified as Escherichia coli (n = 24, 30%), Klebsiella pneumoniae (n = 15, 18.7%), Pseudomonas aeruginosa (n = 16, 20%) and Acinetobacter baumannii (n = 25, 31.2%) were included. Categorical agreements of rapid antimicrobial susceptibility testing at 4-, 6- and 8-hour reading times were 88.1% (304/345), 90.8% (425/468) and 92.3% (467/506), respectively. Major Error rates were 14% (21/150), 4.9% (10/206) and 4/236 (1.7%), whereas Very Major Error rates were 1.1% (2/177), 1.3% (3/232) and 3.3% (8/243), respectively. Results categorized as "Area of Technical Uncertainty" were significantly lower at 8-hour {10.2% (39/384) vs 5.2% (28/534), 4- vs 8-hour, p = 0.003, Fischer's exact test}. Except for a slightly higher Very major error rate, rapid antimicrobial susceptibility testing at 8-hour is equivalent to Disk-diffusion method (CLSI-M100) using CLSI-M52 criteria for equivalence: (Categorical agreement ≥ 90%, Very major error ≤ 1.5% and Major error ≤ 3%). Poor Categorical agreements at all reading times were noted for piperacillin-tazobactam, ciprofloxacin and E. coli. Performance of rapid antimicrobial susceptibility testing methodology in resource limited settings brings unique challenge of identifying micro-organisms within 8 hours. We suggest reading and reporting of results at a single time point using rapid antimicrobial susceptibility testing method i.e. at 8-hour.
Highlights
We prospectively evaluated EUCAST rapid antimicrobial susceptibility testing methodology for susceptibility testing directly from blood culture bottles in comparison to Clinical and Laboratory Standards Institute (CLSI) disk-diffusion method
Our study showed that results of rapid antimicrobial susceptibility testing (RAST) methodology at 6- and 8-hour were equivalent to disk-diffusion method [11], except for slightly higher Major error (ME) rate at 6-hour (4.9%) and Very Major Error (VME) rate at 8-hour (3.3%), when standard cutoffs for equivalence in susceptibility testing methods i.e. Categorical agreement (CA) ≥ 90%, VME ≤ 1.5% and ME ≤ 3%), were applied [14]
Both studies found RAST to be equivalent to AST by VITEK®-2 system, the former [17] at all time points
Summary
We prospectively evaluated EUCAST rapid antimicrobial susceptibility testing methodology for susceptibility testing directly from blood culture bottles in comparison to CLSI disk-diffusion method. Categorical agreements of rapid antimicrobial susceptibility testing at 4-, 6- and 8-hour reading times were 88.1% (304/345), 90.8% (425/468) and 92.3% (467/506), respectively. Conclusions: Except for a slightly higher Very major error rate, rapid antimicrobial susceptibility testing at 8-hour is equivalent to Diskdiffusion method (CLSI-M100) using CLSI-M52 criteria for equivalence: (Categorical agreement ≥ 90%, Very major error ≤ 1.5% and Major error ≤ 3%). Performance of rapid antimicrobial susceptibility testing methodology in resource limited settings brings unique challenge of identifying micro-organisms within 8 hours. We suggest reading and reporting of results at a single time point using rapid antimicrobial susceptibility testing method i.e. at 8-hour. With currently available microbiological diagnostic tools, turnaround time (TAT) of a positive blood culture report with antimicrobial susceptibility testing (AST) results is about 72-96 hours. There is a dire need to provide AST results in clinically meaningful timeframes to improve patient outcomes, reduce broad-spectrum antimicrobial use and limit AMR
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