Multicenter Evaluation of the Etest Gradient Diffusion Method for Ceftolozane-Tazobactam Susceptibility Testing of Enterobacteriaceae and Pseudomonas aeruginosa

Abstract

Ceftolozane-tazobactam (C/T) is a novel beta-lactam-beta-lactamase inhibitor combination antibiotic approved by the U.S. Food and Drug Administration in 2014 for the treatment of complicated intra-abdominal infections (in combination with metronidazole) and complicated urinary tract infections. In this study, we evaluated the performance of the C/T Etest, a gradient diffusion method. C/T Etest was compared to broth microdilution (BMD) for 51 challenge isolates and 39 challenge isolates at three clinical sites. Essential agreement (EA) between the methods ranged from 47 to 49/51 (92.2 to 96.1%) for the , and categorical agreement (CA) ranged from 49 to 51/51 (96.1 to 100.0%). EA and CA for were 100% at all sites. The C/T Etest was also compared to BMD for susceptibility testing on 966 clinical isolates (793 , including 167 and 159 isolates, in addition to 173 isolates) collected at four clinical sites. EA between Etest and BMD was 96.9% for isolates and 98.8% for isolates. Within the , isolates from each species examined had>96% CA. For the clinical isolates, no very major errors were identified but two major errors were found (one for and one for). By BMD, 47.0% of and 46.2% of challenge strains were nonsusceptible to C/T by CLSI breakpoint criteria; 8.2% of clinical isolates and 12.1% of clinical isolates were nonsusceptible to C/T by CLSI breakpoint criteria. In conclusion, Etest is accurate and reproducible for C/T susceptibility testing of and.

Comparative Evaluation of Vitek 2 and Etest versus Broth Microdilution for Ceftazidime/Avibactam and Ceftolozane/Tazobactam Susceptibility Testing of Enterobacterales and Pseudomonas aeruginosa

“…As far as the P. aeruginosa isolates, the C/T Etest yielded excellent results, which were similar to those previously found in a multicenter evaluation using the EUCAST breakpoint [29]. On the contrary, Daragon et al reported higher VME (5.0% and 25.0% when the total number and the number of C/T-resistant isolates were used as the denominator for calculation, respectively) due to a high proportion of strains (19.5%) had C/T MICs close to the EUCAST breakpoint [19].…”

“…On the contrary, Daragon et al reported higher VME (5.0% and 25.0% when the total number and the number of C/T-resistant isolates were used as the denominator for calculation, respectively) due to a high proportion of strains (19.5%) had C/T MICs close to the EUCAST breakpoint [19]. Following the CLSI criteria, previous studies have also confirmed the excellent performance of C/T Etest strips when applied to P. aeruginosa [27,29,30].…”

“…Excellent CA (99%), as well as ME (0%) and VME (1%) rates, were recorded while EA was somewhat lower (88%). Notably, earlier observations reported the Etest as a reproducible and accurate method for C/T susceptibility testing of Enterobacterales using the CLSI (R ≥ 8/4 mg/L) and the former EUCAST (R > 1/4 mg/L) categorization criteria [ 29 ]. Studies using larger numbers of clinical and challenge isolates are needed to assess whether the Etest is reliable for C/T MIC of Enterobacterales based on the current EUCAST breakpoint.…”

Higher MICs (>2 mg/L) Predict 30-Day Mortality in Patients With Lower Respiratory Tract Infections Caused by Multidrug- and Extensively Drug-Resistant Pseudomonas aeruginosa Treated With Ceftolozane/Tazobactam

“…P. aeruginosa was classified as MDR or XDR, as previously defined [20]. C/T susceptibility was determined by e-test [21]. The strain was classified as susceptible if the C/T MIC was ≤4 mg/L, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST).…”

Contemporary analysis of ETEST for antibiotic susceptibility and minimum inhibitory concentration agreement against Pseudomonas aeruginosa from patients with cystic fibrosis

“…All ETEST strips evaluated in this study are cleared by FDA 510 k guidance for P. aeruginosa. Specific to the newer agents, CZA and C/T, a number of studies have reported acceptable performance for ETEST relative to reference BMD [21][22][23][24][25][26]. Notably, none of these studies reported inclusion of CF isolates, which not only may have higher rates of antibiotic resistance, but also more likely to overexpress the alginate exopolysaccharide, develop biofilms, and have a number of unique growth characteristics and phenotypes [27,28].…”