Statement on the assessment of the safety of Cylactin® ( Enterococcus faecium) used in animal nutrition

The European Food Safety Authority (EFSA) published a Scientific Opinion on the safety and efficacy of the product Cylactin® (Enterococcus faecium) as a feed additive for chickens for fattening. In that opinion, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that Enterococcus faecium NCIMB 10415 is free of known virulence factors. Resistance to kanamycin shown in this strain is most likely to be caused by an unknown mechanism that potentiates the effect of the sfkmr gene, and not by acquisition of genes coding for aminoglycosides-modifying enzymes; and is thus not a cause for concern. The European Commission requested EFSA to evaluate the comments raised by the Austrian Authorities thereof during a meeting of the Standing Committee. The Austrian Authorities presented their concerns under eight key points; five of those regarded fundamental statements relating to the use of antibiotics and developing resistance amongst bacteria, which are shared by the FEEDAP Panel. The potential for horizontal gene transfer amongst bacteria is the basis for all the FEEDAP Panel assessments of bacterial additives safety. Consequently, the assessment of Cylactin®, being related to antibiotic resistance, followed the approach documented in the relevant Technical Guidance document prepared by the FEEDAP Panel; in this case, it focused on kanamycin resistance. The minimum inhibitory concentration of E. faecium NCIMB 10415 for kanamycin was found to be higher than the breakpoint identified by the FEEDAP Panel, which triggered a need for the determination of the genetic nature of this resistance. Bioinformatic analyses of the genome sequence of E. faecium NCIMB 10415 demonstrated that none of the known genes coding for high-level aminoglycoside resistance were present. The available evidence demonstrated that the low level resistance to kanamycin shown by this strain of E. faecium results from the presence of two chromosomal genes (aac(6’)-Ii and efmM, synonymous with sfkmr), which are intrinsic to all E. faecium strains studied to date. Gene inactivation experiments conducted with this strain confirmed that no other genetic determinants of resistance to kanamycin were involved. The gene aac(6’)-Ii does not confer high-level resistance to amikacin in E. faecium. The FEEDAP Panel reiterates its former conclusions that: (i) the genetic determinants conferring kanamycin resistance to E. faecium NCIMB 10415 are intrinsic to E. faecium, (ii) the risk of horizontal transfer of these genes is minimal, and (iii) the use of Cylactin® in animal nutrition would not increase the prevalence of aac(6’)-Ii and efmM genes in the environment.