Klinisk institutt 2

Midtveisevaluering - Christoffer Lindemann




Aminoglycoside resistance in Escherichia coli


During the past decade, gentamicin resistance in E. coli has reached 8 % in Norway. This increasing aminoglycoside resistance is of great concern as it threatens our current empirical treatment of sepsis. Aminoglycoside modifying enzymes (AME) encoded by genes situated on mobile genetic elements, is the most frequent mechanism of resistance. This project aims to investigate the prevalence and cause of aminoglycoside resistance in Norway. Through in depth investigation of resistant isolates by whole genome sequencing and advanced proteomic analysis, the project will provide a better understanding of mechanisms involved in aminoglycoside resistance and regulatory control of relevant resistance genes. Investigation of the transferability of AME will give insights into the horizontal spread of aminoglycoside resistance among bacteria. 


Results has so far shown a prevalence in Western Norway comparable to the rest of Norway. Two AME were found to be the most prevalent cause of resistance to gentamicin and tobramycin. There is a high level of co-resistance, especially to ciprofloxacin. Resistance to aminoglycosides occurs more frequently in isolates producing extended spectrum beta-lactamases (ESBL). The genome of twelve clinical isolates of E. coli has been sequenced and will provide important information for both proteomic analysis and the investigation for regulatory control and transferability of the resistance genes.


Preliminary results suggest that the cause of aminoglycoside resistance in Norway is not solely due to the use of gentamicin and tobramycin, but is more likely to be a consequence of co-selection from increased use of quinolones and broad-spectrum beta-lactam antibiotics.