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Journal of Clinical Microbiology, June 2001, p. 2298-2299, Vol. 39, No. 6
Department of Cell Biology and Molecular
Genetics1 and Department of Biological
Resources Engineering,4 University of
Maryland, College Park, Maryland 20742; Veterans Affairs
Maryland Health Care System, University of Maryland School of
Medicine, Baltimore, Maryland 21201-15952; and
Center for Veterinary Medicine, U.S. Food and Drug
Administration, Laurel, Maryland 207083
Received 6 November 2000/Returned for modification 1 February
2001/Accepted 27 March 2001
The occurrence of resistance to the streptogramin
quinupristin-dalfopristin in Enterococcus faecium isolates
from chickens on the Eastern Seaboard, was evaluated.
Quinupristin-dalfopristin resistance was found in 51 to 78% of
E. faecium isolates from the food production environment.
The high level of resistance in this organism suggests that this
reservoir of resistance may compromise the therapeutic potential of
quinupristin-dalfopristin.
Vancomycin has largely been reserved
to treat multiresistant Enterococcus sp. infections and
methicillin-resistant Staphylococcus aureus (MRSA)
infections; however, resistance has become so prevalent over the past
10 years as to present a crisis situation. Faced with a potentially
untreatable pathogen, the U.S. Food and Drug Administration (FDA) has
approved use of the streptogramin quinupristin-dalfopristin (Synercid)
to treat infections caused by vancomycin resistant enterococci (VRE).
Reports from German health agencies suggest that human carriage of
quinupristin-dalfopristin-resistant Enterococcus faecium
occurs at a rate of 14% (11). Although resistance to quinupristin-dalfopristin has been observed in the United States, there
is insufficient information, as yet, to determine the incidence in the
nonhospitalized community. These observations illustrate that a pool of
resistance to this antibiotic can be found in the human microbiota. In
the absence of selective pressure through clinical administration of
the drug, the means by which these isolates acquired resistance has yet
to be fully clarified. One possible source of resistance development
may have been the use of an analogue of quinupristin-dalfopristin,
virginiamycin, in poultry production. Virginiamycin has been used in
the United States for more than 25 years to control clostridial
diseases and subtherapeutically to promote the growth of commercial
poultry. As part of a larger study examining multiresistant enterococci from poultry in a region of the Eastern Seaboard, we have discovered an
unusually high prevalence of quinupristin-dalfopristin resistance in
E. faecium isolated from chickens.
Sixty-seven samples were collected from poultry transport containers
(PTC), litter samples, and cloacal swabs. Swabs taken from nine PTC
from six farms were used to inoculate colistin-nalidixic acid (CNA)
agar plates. Seventeen poultry floor litter samples from 14 different
farms were added at a 1:4 dilution to nalidixic acid-brain heart
infusion-salt (NABS) enrichment broth for incubation at 35°C and were
subsequently streaked onto CNA agar plates (5). Forty-one
cloacal swabs were rinsed in tryptic soy broth (TSB) and spread plated
onto either CNA or cephalexin aztreonam arabinose (CAA) agar
(3) supplemented with 10 µg of
quinupristin-dalfopristin/ml and 4 µg of ampicillin/ml. Colonies
suspected to be Enterococcus spp. were isolated and
identified using a modification of the protocol described by Facklam
and Collins (2). Susceptibilities of E. faecium
isolates to quinupristin-dalfopristin were assayed using the
Kirby-Bauer disk diffusion methodology on Mueller-Hinton agar (with
resistance defined as a zone of >15 mm) or by use of the Sensititre
antimicrobial testing system with a breakpoint MIC of >2 µg/ml
(7, 8).
Twenty-one (51.2%) of 41 E. faecium isolates from cloacal
swabs taken from chickens were resistant to quinupristin-dalfopristin. Of the 27 E. faecium isolates from PTC swabs and litter
samples, 21 (77.7%) were resistant (Table
1). Variance in the observed quinupristin-dalfopristin resistance incidence is likely due to the
differences in sampling methodology as well as to differences in
colonization or carriage rates among flocks.
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.6.2298-2299.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
High-Frequency Recovery of Quinupristin-Dalfopristin-Resistant
Enterococcus faecium Isolates from the Poultry
Production Environment
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TABLE 1.
Profile of susceptibilities of E. faecium
isolates of poultry origin to quinupristin-dalfopristin
The high rate of recovery of quinupristin-dalfopristin-resistant E. faecium from chickens in the United States was troubling, but not surprising, given the routine application of the selective agent virginiamycin to poultry feed. Welton et al. have reported that virginiamycin-resistant E. faecium prevalence in domestic turkeys from Michigan can be as high as 100% because of the lengthy exposure of flocks to virginiamycin (10). Resistance development in chickens is significant in that the growout period for broiler chickens is 6 to 8 weeks versus the 16 to 19 weeks required for turkeys. In addition, per capita consumption of chicken products in the United States exceeds that of turkey by a factor of 4.3 (9).
Various plasmid-borne genetic elements, which carry quinupristin-dalfopristin resistance in agriculturally derived E. faecium, have been demonstrated to cross into E. faecium isolates of human origin in vitro (4). This finding was unsettling because of the problems that hospital physicians currently encounter in controlling nosocomial VRE. While VRE with resistance to quinupristin-dalfopristin have not yet emerged as a problem in the clinical setting, it is possible that this resistance pattern will eventually occur. Indeed, the incidence of quinupristin-dalfopristin-resistant VRE has been reported to be 7.4% in German hospitals in 1998 (6). In fact, a recent report has shown that genes for quinupristin-dalfopristin resistance and vancomycin resistance were found on the same plasmid in an Enterococcus isolate from France (1).
Although the use of antibiotics at subtherapeutic concentrations in agriculture in the United States has not been definitively established as a contributor to the rising problem of antibiotic resistance in human clinical medicine, the presence in the food production environment of a population of E. faecium that harbors mobile resistance elements to quinupristin-dalfopristin is cause for concern. The European Union has banned the use of subtherapeutic antibiotics in agriculture as a precautionary measure due to a presumed risk to human health. The possibility that these strains may infect humans or that resistance elements may cross to the human microbiota, notably E. faecium, represents sufficient risk to warrant broader and continuous surveillance in the United States.
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ACKNOWLEDGMENTS |
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This research was supported by a grant from the Joint Institute for Food Safety and Applied Nutrition (JIFSAN), University of Maryland, College Park.
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FOOTNOTES |
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* Corresponding author. Mailing address: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742. Phone: (301) 405-5452. Fax: (301) 314-9489. E-mail: sj13{at}umail.umd.edu.
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