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

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.