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U.S. Department of Health and Human Services

Animal & Veterinary

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by Simjee S, White DG, McDermott PF, Wagner DD and Walker RD
FDA Veterinarian Newsletter 2002 Volume XVI, No IV

There have been several worldwide studies docu-menting the relatedness of vancomycin resistant Enterococcus faecium (VREF) isolates and a Tn1546 element, which confers glycopeptide resistance, found in animals and humans. Recently, 24 Tn1546 types were described from Europe and the United States. Some types were specific to human or animal VREF isolates, while others were common to both human and animal VREF isolates. Of the 24 VREF Tn1546 types two specific forms of Tn1546 (designated F1 and F2) are unique to human VREF isolates found only in the USA (Figure). In isolates unique to the United States, Tn1546 shows a deletion of 889 bp in ORF1and an insertion of IS1216V. In addition there is an insertion of IS1251 between vanS and vanH. The only difference between F1 and F2 types is a single base change, C9692 Õ T.

Epidemiological studies from Europe suggest that VREF are horizontally transmitted from animals to humans. However, there have been no reports of high-level vancomycin resistance (>32 µg/ml) in E. faecium from animals in the United States. In view of the possible involvement of companion animals in the spread of antibiotic resistant enterococci to humans, we conducted a study to characterize gentamicin and vancomycin resistance among enterococci isolated from dogs presented with urinary tract infections at the Veterinary Teaching Hospital at Michigan State University over a two-year period (1996-1998).

Isolated species included E. faecium (n=13), E. faecalis (n=7), E. gallinarum (n=11), and E. casseliflavus (n=4). We found a single canine E. faecium isolate that showed both high level aminoglycoside and high level vancomycin resistance. Gene transfer experiments concluded that the vancomycin and gentamicin resistance genes were transferable independently of each other, ruling out the possibility of gene linkage. When we further characterized the vancomycin resistance determining elements we found that the vanA gene was part of Tn1546. Detailed molecular analysis of Tn1546 showed it to be identical to the F1 type described above and shown in the Figure.

To determine whether this isolate was a canine E. faecium clone or a human VREF clone we conducted pulsed field gel electrophoresis (PFGE) studies. When we compared the canine VREF PFGE pattern to more than 63 different human VREF PFGE types no match was found. However, a match was found with another, non-VREF, canine E. faecium isolate that displayed high level gentamicin resistance but was susceptible to vancomycin. This would lead us to conclude that the canine VREF is indeed a canine E. faecium clone that has acquired the Tn1546 from an external source.

Several speculations can be made as to how a canine E. faecium strain may have acquired a Tn1546 that, to date, has only been described in VREF isolated from humans in the United States. Although direct selection pressure would be the most likely cause of acquisition of Tn1546, there is no record of the dog being administered vancomycin for treatment of its UTI. Additionally, it may be possible that either the dog owner or a member of the veterinary hospital staff attending to the dog was the source of the bacterium carrying the VREF transposon. Although this seems like a feasible route, no samples from either the dog owner or attending hospital staff are available for analysis.

In summary, we have described the first U.S. report of a Tn1546 transposon in a VREF canine isolate that is indistinguishable from Tn1546 found in VREF human isolates. These data demonstrate that exchange of resistance determinants between human and canine enterococcal strains can occur. The potential role that companion animals may play in the dissemination of genes conferring clinically relevant resistance among enterococci requires further study.