A Comparison of Ceftazidime-avibactam Antimicrobial Susceptibility Testing Methods (Disk Diffusion, Gradient Diffusion and Broth Micro-dilution) amongst Klebsiella pneumoniae OXA-48-like producing isolates

Abstract

Background: The use of ceftazidime-avibactam for the treatment of infections caused by Enterobacterales harbouring serine carbapenemases, most notably Klebsiella pneumoniae, is well established worldwide. This agent is particularly useful for blaOXA-48-like infections. However, there is currently no data from the South African setting for the comparison of manual susceptibility testing methods against reference method for this agent. It was the aim of this study to determine the performance of disk diffusion and gradient diffusion antibiotic susceptibility testing methods compared to broth microdilution (BMD) in a collection of OXA-48-like producing Klebsiella pneumoniae isolates. Methods: De novo ceftazidime-avibactam susceptibility testing was performed on 100 stored Klebsiella pneumoniae blaOXA-48-like clinical isolates collected between 2017 and 2023. Disk diffusion and gradient diffusion testing was conducted as per Clinical Laboratory and Standards Institute guidelines and BMD using Sensititre™ (Thermo Fischer, Massachusetts, USA). Categorical and essential agreement as well as precision were compared to BMD. Results: Categorical agreement for disk diffusion and gradient diffusion was 100% (100/100) while essential agreement was 97% (86/88) for gradient diffusion versus BMD. No major or very major errors were observed. All isolates tested susceptible to ceftazidime-avibactam, with the BMD MIC50/90 at 1/4 and 2/4 μg/mL and gradient diffusion MIC50/90 at 0.5/4 and 1/4 μg/mL, respectively. 2 Conclusions: Disk diffusion and gradient diffusion are reliable alternative methods for determining ceftazidime-avibactam susceptibility in susceptible isolates of Klebsiella pneumoniae OXA- 48-like producers.