Performance of ceftazidime/avibactam susceptibility testing methods against clinically relevant Gram-negative organisms

Abstract

Objectives To ensure the accuracy of susceptibility testing methods for ceftazidime/avibactam. Methods The performances of the Etest (bioMérieux), 30/20 μg disc (Hardy diagnostics) and 10/4 μg disc (Mast Group) were evaluated against the reference broth microdilution (BMD) method for 102 clinically relevant Gram-negative organisms: 69 ceftazidime- and meropenem-resistant Klebsiella pneumoniae and 33 MDR non-K. pneumoniae. Essential and categorical agreement along with major and very major error rates were determined according to CLSI guidelines. Results A total of 78% of isolates were susceptible to ceftazidime/avibactam. None of the three methods met the defined equivalency threshold against all 102 organisms. The Etest performed the best, with categorical agreement of 95% and major errors of 6.3%. Against the 69 ceftazidime- and meropenem-resistant K. pneumoniae, only the Etest and the 10/4 μg disc met the equivalency threshold. None of the three methods met equivalency for the 33 MDR isolates. There were no very major errors observed in any analysis. These results were pooled with those from a previous study of 74 carbapenem-resistant Enterobacteriaceae and data from the ceftazidime/avibactam new drug application to define optimal 30/20 μg disc thresholds using the error-rate bound model-based approaches of the diffusion breakpoint estimation testing software. This analysis identified a susceptibility threshold of ≤19 mm as optimal. Conclusions Our data indicate that the Etest is a suitable alternative to BMD for testing ceftazidime/avibactam against ceftazidime- and meropenem-resistant K. pneumoniae. The 30/20 μg discs overestimate resistance and may lead to the use of treatment regimens that are more toxic and less effective.

Performance Evaluation of the Gradient Diffusion Strip Method and Disk Diffusion Method for Ceftazidime–Avibactam Against Enterobacterales and Pseudomonas aeruginosa: A Dual-Center Study

“…All these three values are very close to 20 mm. The findings were consistent with those of a previous report when the disk diffusion method had more VME and was a universal result ( Zhou et al, 2018 ; Wenzler et al, 2019 ; Wang et al, 2020 ). Most of carbapenemase-non-producing resistant P. aeruginosa isolates (11/14) exhibited low-level resistance (MIC was 16/4 or 32/4 mg/l), which is a point of concern.…”

Performance of Ceftazidime-Avibactam 30/20-μg and 10/4-μg Disks for Susceptibility Testing of Enterobacterales and Pseudomonas aeruginosa

“…The two ceftazidime-avibactam disk diffusion tests with Enterobacterales isolates reached 95% CA, and the VME rates (0.5% and 1.5%) were acceptable ( 13 , 14 ). The ceftazidime-avibactam 10/4-μg disk diffusion test performed well with the tested Enterobacterales isolates (CA, 99.8%) and P. aeruginosa isolates (CA, 87.9%), but a high ME rate (15.5%) occurred with P. aeruginosa isolates.…”

“…Concerningly, the ceftazidime-avibactam automated susceptibility system is not widely applied in China, and the reference broth microdilution (BMD) method is difficult for routine microbiology laboratories to perform. Although Etest has demonstrated exemplary performance for ceftazidime-avibactam susceptibility testing with Enterobacterales and P. aeruginosa isolates ( 11 – 13 ), it is costly. To sum up, the disk diffusion test is the optimal option in most laboratories, because it is convenient, economical, and practical; however, there are some drawbacks to the disk diffusion test, such as different specifications and manufacturers, subjective measurements, and inoculum effects.…”

Susceptibility of Meropenem-Resistant and/or Carbapenemase-Producing Clinical Isolates of Enterobacterales (Enterobacteriaceae) and Pseudomonas aeruginosa to Ceftazidime-Avibactam and Ceftolozane-Tazobactam as Assessed by In Vitro Testing Methods

“…We purposely tested Enterobacteriaceae or P. aeruginosa isolates for which the probability of being resistant to CZA and/or C/T was relatively high [ 14 , 15 , 16 ]. Indeed, our reliability assessment of (VITEK 2 AST-N397 card or ETEST) AST methods used Enterobacteriaceae (66/153 and 153/153) or P. aeruginosa (26/52 and 31/52) isolates whose Micronaut AST MICs to CZA and C/T, respectively, fall within the EUCAST resistant category (CZA MICs, >8/4 µg/mL; C/T MICs, >2/4 µg/mL for Enterobacteriaceae and >4/4 µg/mL for P. aeruginosa ).…”