Establishing piperacillin-tazobactam susceptibility in ceftriaxone non-susceptible Enterobacterales: comparing disk diffusion, Etest, and VITEK 2 automated minimal inhibitory concentration measurements vs. broth microdilution

Objectives: Post-hoc analyses of the MERINO trial highlight the uncertainty associated with establishing piperacillin-tazobactam (PTZ) susceptibility in extended-spectrum beta-lactamase-producing Enterobacterales. Herein, we compare the concordance of susceptibility for PTZ among the VITEK 2, disc diffusion, and Etest with broth microdilution (BMD) as the reference standard.

Methods: Ninety-four consecutive ceftriaxone non-susceptible Escherichia coli and Klebsiella pneumoniae bloodstream isolates were identified from patients at three hospitals in Montréal, Québec. BMD was used as the reference standard against which disc diffusion, VITEK 2 (AST-N391), and Etest susceptibility testing were compared. Errors were categorized as very major (false susceptible), major (false resistant), and minor (other).

Results: Overall, 68/94 (72.3%) of isolates were susceptible to PTZ by BMD. Disc diffusion made no major or very major errors (0%; 97.5% CI: 0-3.8%). The VITEK 2 system had a major error rate of 2.5% (95% CI: 0.003-0.089%) and a very major error rate of 26.7% (95% CI: 0.08-0.55%); however, all isolates with VITEK 2 minimal inhibitory concentrations (MICs) of ≤4 μg/mL were susceptible. Finally, the Etest had a major error rate of 6.3% (95% CI: 0.02-0.14%), but no very major errors. Combining VITEK 2-determined susceptibility with a second test led to an increase in the number of correctly classified susceptible organisms.

Discussion: The VITEK 2 system, and to a lesser extent the Etest, risk major errors. Used alone, the VITEK 2 system also risks very major errors if the estimated MIC is > 4 μg/mL. Combining VITEK 2 with disc diffusion in isolates with an estimated MIC of 8-16 μg/mL could prevent both major and very major errors.