Susceptibility of MDR Pseudomonas aeruginosa to ceftolozane/tazobactam and comparison of different susceptibility testing methods

Abstract

Background: Infections caused by MDR Pseudomonas aeruginosa are on the rise, particularly in critically ill patients. Therefore, there is a need to evaluate new antimicrobial regimens. The objectives of this study were to investigate the ceftolozane/tazobactam resistance rates of MDR and XDR P. aeruginosa, the underlying resistance genes, the clonal structure and different antimicrobial susceptibility testing (AST) methods regarding their accuracy for ceftolozane/tazobactam testing.

Methods: In total, 112 MDR and XDR P. aeruginosa (from infection and colonization) from one German tertiary care hospital were included (2013-16). AST was done using broth microdilution (BMD), gradient diffusion test strips and disc diffusion. Resistance genes were screened by PCR. A randomly selected subset of 77 isolates was subjected to WGS to assess the clonal structure.

Results: In total, 38 isolates (33.9%) were resistant to ceftolozane/tazobactam according to the BMD reference method. Resistance was significantly lower in MDR P. aeruginosa (4.8%) compared with XDR P. aeruginosa (50%, P < 0.0001). The underlying mechanism in carbapenemase-positive ceftolozane/tazobactam-resistant isolates (n = 38) was blaIMP (n = 25), blaVIM (n = 4) and blaGES (n = 1). The resistance mechanism of the remaining eight ceftolozane/tazobactam-resistant isolates remained unclear. Although our strain collection was diverse, resistance to ceftolozane/tazobactam was almost exclusively associated with MLST ST235. The disc diffusion method was accurate for ceftolozane/tazobactam AST (no false-susceptible results, categorical agreement = 92.9%).

Conclusions: Ceftolozane/tazobactam resistance was low in MDR P. aeruginosa, but higher in XDR P. aeruginosa. The disc diffusion method showed an acceptable accuracy for ceftolozane/tazobactam AST.