Comparison of methods to analyse susceptibility of German MDR/XDR Pseudomonas aeruginosa to ceftazidime/avibactam

•64.1% of multi-drug-resistant/extensively drug-resistant (MDR/XDR) Pseudomonas aeruginosa were susceptible to ceftazidime/avibactam.•Only one gradient diffusion test was acceptable as an alternative to broth microdilution for susceptibility testing.•Ceftazidime/avibactam-resistant MDR/XDR P. aeruginosa mainly belong to blaIMP-positive ST235. Ceftazidime/avibactam (CZA) is a new β-lactam/β-lactamase inhibitor combination with promising properties as avibactam can inhibit a broad range of β-lactamases (e.g. blaKPC, blaOXA-48). The objectives of this study were: (i) to assess CZA susceptibility rates; (ii) to compare gradient and disk diffusion tests with broth microdilution (BMD) for CZA susceptibility testing; and (iii) to study the clonal structure and antimicrobial resistance genes in multi-drug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa. Isolates (n=192) from routine diagnostics (Germany, 2013–2018) were tested by BMD reference method, gradient diffusion test (Etest, bioMérieux and MIC Test Strip, Liofilchem) and disk diffusion test (MAST and Oxoid). All isolates were whole-genome sequenced to screen for metallo-β-lactamases and to assess the clonal structure using core-genome multi-locus sequence typing. In total, 64.1% of isolates (n=123) were susceptible to CZA (minimum inhibitory concentration required to inhibit the growth of 50% of organisms 8 mg/L, minimum inhibitory concentration required to inhibit the growth of 90% of organisms >256 mg/L, range 0.5–>256 mg/L). Susceptibility rates were higher in MDR (85.0%) than in XDR (49.1%) P. aeruginosa. Among commercial susceptibility testing methods, Etest showed highest accuracy in comparison to BMD (essential agreement 94.8%, categorical agreement 94.3%). CZA-resistant isolates (n=69) mainly belonged to ST235 (n=29, blaIMP-positive). In conclusion, CZA is a promising treatment option for infections caused by MDR P. aeruginosa. CZA-resistant P. aeruginosa mainly belong to the pandemic ST235 high-risk clone. Etest can be considered as an alternative to BMD.