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Commentary
Antibiotics in Animal Feed
and Spread of Resistant Campylobacter from Poultry to Humans
Nicole M. Iovine* and Martin J. Blaser*†
*New York University School of Medicine, New York, New York, USA; †and
New York Harbor Department of Veterans Affairs Medical Center, New York,
New York, USA
Suggested citation
for this article:
Iovine NM, Blaser MJ. Antibiotics in animal feed and spread of resistant
Campylobacter from poultry to humans. Emerg Infect Dis [serial
on the Internet]. 2004 Jun [date cited]. Available from: http://www.cdc.gov/ncidod/EID/vol10no6/04-0403.htm
Contamination of food with potentially dangerous human pathogens has
been recognized since the time of Pasteur (1) and is
well-documented in the modern era (2), but the development
of antimicrobial agents has helped limit the consequences of such infections.
Concomitantly, the widespread use of antimicrobial agents has also led
to the emergence of antimicrobial drug–resistant organisms (3,4).
Gupta et al. demonstrate the increasing prevalence in the United States
of ciprofloxacin-resistant Campylobacter species isolated from
humans and poultry from 1990 to 1997, and their studies implicate the
prophylactic treatment of poultry with fluoroquinolones in this emerging
problem (5). Their report indicates that the source of
fluoroquinolone-resistant Campylobacter infections was consuming
poultry colonized with resistant strains (Figure),
rather than selection for Campylobacter resistance in the human
gut after clinical fluoroquinolone use to treat the diarrheal illness
(5). This work provides further evidence that fluoroquinolone
use in poultry promotes the emergence of resistant Campylobacter
strains that subsequently infect humans (6). That persons
infected with these fluoroquinolone-resistant strains had 3 additional
days of illness and were more likely to be hospitalized demonstrates the
harm caused by such resistant stains (5).
Since campylobacters are normal enteric flora in many avian species,
poultry represents a model system to test the hypothesis that prophylactic
and growth-promoting use of antimicrobial agents in food animals selects
for the emergence of antimicrobial drug–resistant organisms. In one study,
chickens that were naturally colonized with fluoroquinolone-susceptible
Campylobacter strains began to excrete resistant strains after
2 days of doses of enrofloxacin (7), which is commonly
used for prophylaxis in the poultry industry. A single point mutation
in gyrA encoding the bacterial DNA gyrase was sufficient to confer
high-level resistance (7,8). This small genetic change
apparently has a low "fitness cost" to the organism, as evidenced
by fluoroquinolone-resistant strains' rapidly replacing susceptible Campylobacter
in treated chickens (7). Developing an animal reservoir
of fluoroquinolone-resistant Campylobacter has been the major factor
behind transmission of quinolone resistance to humans (8,9).
In contrast, among poultry treated therapeutically with enrofloxacin,
no resistance was observed in the 13 C. jejuni isolates tested
(9). Similarly, after the prophylactic and growth-promoting
uses of macrolides in swine were banned in Denmark, the prevalence of
macrolide-resistant C. coli declined (10). Thus,
the major determinant of developing resistance appears to be use of subtherapeutic
antimicrobial doses. The antimicrobial drug ban in Denmark did not decrease
the amount of meat produced by the poultry and pig production industries,
which removed a major concern (10). Evidence suggests
that restricting fluoroquinolone use to therapeutic indications only in
food animals could decrease rates of fluoroquinolone-resistant Campylobacter,
and the Danish experience with macrolide restriction proves that such
limitations need not harm the husbandry of food animals.
The increased likelihood of foreign travel in persons infected with ciprofloxacin-resistant
strains (5) illustrates the global threat posed by resistant
strains. Appreciating such realities favors concerted efforts to limit
use of fluoroquinolones (and other antimicrobial drugs) to therapy only
in food animals. This view was supported by a recent (March 2004) landmark
decision by Federal Drug Administration Administrative Law Judge Daniel
J. Davidson, withdrawing approval for the new animal drug application
to use enrofloxacin for prophylaxis or growth-promotion in poultry (11).
This decision was the first occasion that a previously approved antimicrobial
agent was removed from the U.S. veterinary market because of concerns
about antimicrobial drug resistance. With this decision as precedent,
we should follow the examples set in Europe and ban use of all antimicrobial
agents in food animals, except when necessary for therapy of ill animals.
Dr. Iovine is a
fellow in the Division of Infectious Disease and a post doctoral fellow
in the Department of Microbiology at New York University. She studies
the interactions between human enteric pathogens and innate host immunity.
Dr. Blaser is the
Frederick H. King Professor and chair of the Department of Medicine,
and Professor of microbiology at New York University. He has been studying
Campylobacter infections since 1977.
References
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