Aminoglycoside resistance in clinical Gram-negative isolates from Norway

Abstract

Aminoglycosides represent an important class of antimicrobial agents. The prevalence of aminoglycoside resistance among Gram-negative bacteria in Norway is low, but an increased prevalence among clinical isolates of Escherichia coli has been observed during the last years. The most prevalent resistance mechanism is aminoglycoside modifying enzymes. In addition, resistance may occur when bacteria produces 16S rRNA methylases, which causes high level and broad-spectrum aminoglycoside resistance. In this study, we analysed the susceptibility pattern of different aminoglycosides in different Norwegian strain collections of E. coli, Klebsiella spp. and Pseudomonas aeruginosa. Among E. coli and Klebsiella spp. isolates from the Norwegian surveillance programme for antimicrobial resistance (NORM) 2009 the prevalence of reduced susceptibility to tobramycin (4.1%) was slightly higher compared to gentamicin (3.8), in blood culture isolates of E. coli and 2% and 1.4% in in blood culture isolates of Klebsiella spp., respectively. The prevalence of reduced susceptibility to amikacin was low in both species; 0.6% in E. coli and 0.4% in Klebsiella spp. In a collection of ESBLA-positive Enterobacteriaceae isolates the prevalence of reduced susceptibility was much higher with 56% and 44% of the isolates showing reduced susceptibility to tobramycin and gentamicin, respectively. The prevalence of reduced susceptibility to amikacin (7%) was also lower than for tobramycin and gentamicin in the ESBLA-positive isolates. The same pattern was also observed in the collection of carbapenem non-susceptible P. aeruginosa isolates. In both Enterobacteriaceae collections the aminoglycoside modifying enzymes AAC(3)-II and AAC(6’)-Ib were the dominating enzymes causing aminoglycoside resistance. The 16S rRNA methylases rmtB and rmtD were detected in one E. coli and one P. aeruginosa isolate resistant to all aminoglycosides tested, respectively. Three different methods for detection of reduced susceptibility were used; Etest, EUCAST disk diffusion and VITEK2 AST. The results from the three methods were compared. Discrepancies were mainly observed when comparing Etest and EUCAST disk diffusion for detecting tobramycin resistance in Enterobacteriaceae, and comparing Etest and EUCAST disk diffusion for detecting gentamicin resistance in P. aeruginosa. In conclusion, aminoglycoside resistance in Norway is low, but increasing. Worryingly, aminoglycoside resistance is coupled with other resistance mechanisms such as ESBLA resulting in multidrug resistance limiting treatment options. Method comparison indicates a need for evaluation and frequent maintenance of breakpoints.