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U.S. Department of Health and Human Services

Animal & Veterinary

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Use of Antimicrobials in Hatcheries: A Field Assignment

by Linda E. Silvers, D.V.M., M.P.H. and Charlotte D. Spires, D.V.M., M.P.H., D.A.C.V.P.M.
FDA Veterinarian Newsletter January/February 2002 Volume XVII, No 1

Recently, the Centers for Disease Control and Prevention (CDC) reported the emergence of domestically acquired ceftriaxone-resistant Salmonella in humans in the U.S. This antimicrobial resistance was detected by the routine surveillance of the National Antimicrobial Resistance Monitoring System (NARMS). Because ceftriaxone-resistant Salmonella has become a public health concern, the Center for Veterinary Medicine (CVM) Office of Surveillance and Compliance issued a high priority assignment directed at identifying the use of ceftiofur and other antimicrobial drugs in a nationally representative sample of poultry hatcheries in the United States.

Historically, populations of bacteria have impacted human and animal health, without facing much of a challenge to their own well-being. That situation changed in the early 1940's, as antimicrobial drugs, the first significant weapons in the fight against bacterial illnesses, were widely marketed. While antimicrobial drugs have been an extremely effective treatment, over time, bacteria that are resistant to antimicrobial drugs have emerged.

Today, almost all bacteria that were universally susceptible to antibiotics are now resistant to at least some of these drugs, and some bacteria are resistant to many different antibiotics.1 Selective pressure exerted by antimicrobial drug use can result in the development of antimicrobial resistance.2 The use of antimicrobials in human medicine as well as in food animal production may promote this type of selection.3 Antimicrobial drugs are used in animal agriculture to treat disease, to prevent disease, and to promote growth/feed efficiency. While it is known that the administration of antimicrobials to food animals can select for resistance among bacteria which may subsequently be passed to humans through the consumption of food or by direct contact, the exact magnitude of the human health impact has been difficult to quantify.

Some human bacterial infections acquired from food animal sources may not respond to antimicrobial drugs chosen for treatment because a similar drug was given to the food animal and resulted in the development of resistant organisms.

Approximately 1.4 million cases of salmonellosis occur in the U.S. each year, most in children and the elderly, and an estimated 600 of these cases are fatal.4 Ceftriaxone, a third generation cephalosporin, is the drug of choice for treating invasive Salmonella infections. Resistance to this drug is a concern, particularly in children, since fluoroquinolones, an alternative treatment, are not approved for use in children.4

Because of cross-resistance between the veterinary drug ceftiofur and the human drug ceftriaxone, and because food animals are the predominant source of domestically acquired Salmonella infections, ceftiofur use may be contributing to ceftriaxone-resistant Salmonella which are subsequently acquired by people via food consumption or by direct contact. Ceftiofur is the only expanded spectrum cephalosporin drug approved for systemic use in food animals in the U.S. This drug is currently approved for therapeutic use in cattle, swine and poultry. The majority of cephalosporin-resistant Salmonella express an extended-spectrum -lactamase, which is able to hydrolyze oxyimino cephalosporins and monobactams, but not the cephamycins. However, recent reports indicate that several organisms of Enterobacteriaceae have obtained plasmids encoding AmpC-like-lactamases that hydrolyze the cephalosporins as well as the cephamycins such as cefoxitin and ceftriaxone. Resistance to ceftriaxone and ceftiofur is mediated by a cephalomycinase (CMY) encoded by the blaCMY gene, and eleven blaCMY variants have been described to date. Recent research conducted in the Office of Research at CVM identified plasmid-mediated AmpC-like-lactamases in E. coli and Salmonella isolated from food animals and retail meats. These blaCMY genes were further shown to be transferred between different bacteria.5

The Assignment Memorandum included a six-page questionnaire to identify hatchery compliance with 21 CFR Part 530, which addresses extralabel drug use in animals. Extralabel drug use is legal if requirements in the regulation are satisfied (e.g., use of the drug by or on the lawful order of a licensed veterinarian within the context of a valid veterinary-client-patient relationship). Prior notice was not given to personnel at inspected sites. The Assignment Memorandum, which was sent to District Directors, Directors of Investigation Branches, and FDA District Offices, required the following actions: Inspection of the hatchery to determine compliance with 21 CFR 530, completion of all inspections during FY01, coordination of follow-ups by Districts so that as many visits as possible could be conducted on the same day and collaboration with CVM so that a representative from the Division of Epidemiology could work with Field Personnel during each inspection. Directions to Field Personnel included: 

  1. Review all medication/treatment records to identify antimicrobials used by the firm, 
  2. Review labels on the drugs found at each site to ensure that use is per approved label directions, and 
  3. Evaluate any extralabel use to determine if the drug was prescribed by a veterinarian within the context of a valid veterinary-client-patient relationship and satisfied other requirements of 21 CFR Part 530.

The hatcheries inspected were randomly selected in an effort to focus on use patterns that are representative of most poultry hatcheries in the U.S. Epidemiologists and microbiologists from CVM's Division of Epidemiology collaborated with local FDA field investigators as well as with members of CVM's Division of Compliance to inspect 37 chicken and turkey hatcheries. The size of the hatcheries and the types of operations varied. A questionnaire that captured use information for ceftiofur and other antimicrobials such as gentamicin (an aminoglycoside antimicrobial drug approved for use in poultry), was administered, and a site inspection was conducted at each hatchery. Data collected included demographic information, current and past ceftiofur and gentamicin usage, routes of administration, doses administered, number of chicks or poults produced at the facility and the proportion of chicks or poults treated with the antimicrobial drug.

Biosecurity suits, hats and shoe covers were necessary in several hatcheries. In most instances, the hatcheries supplied the inspectors with all of the necessary items that were needed to meet their biosecurity requirements. These ranged from no precautions to shower in-shower out facilities.

On September 11th, when the terrorism attacks occurred, six Division of Epidemiology members were in travel status due to this field assignment. As a consequence, several travel itineraries were affected. This disruption necessitated extension of the assignment beyond the FY01 deadline for completion.

Generally, interviewees from the various hatcheries were very cooperative and provided all of the information that was requested. Some hatcheries were not inspected for various reasons. In some instances, the hatcheries were no longer operational. In one instance, the hatchery was at a university research facility which only raised chicks for research purposes. When possible, alternate hatcheries in the area were identified. A total of 27 commercial hatcheries (22 chicken, 4 turkey, 1 combination) were actually inspected. The data is currently being compiled and analyzed.

References

  1. Levy SB. The antibiotic paradox. New York: New York; 1992.
  2. American Society of Microbiology. Report of the ASM Task Force on Antimicrobial Resistance. Washington, DC March 1995.
  3. Smith KE, Bender JB, Osterholm MT. Antimicrobial resistance in animals and relevance to human infections. In: Nachamkin I, Blaser MJ, editors. Campylobacter. 2nd ed.Washington, DC: ASM Press; 2000. P.483-138.
  4. Fey PD, Safranek TJ, Rupp ME, Dunne EF, Ribot E, Iwen PC, Bradford PA, Angulo FJ Hinrichs SH. Ceftriaxone-resistant Salmonella infection acquired by a child from cattle. New England Journal of Medicine 2000;342(7):1242-1249.
  5. Zhao S, White GD, McDermott FP, Friedman S, English L, Ayers S, Meng J, Maurer JJ, Holland R, Walker DR. Identification and Expression of Cephamycinase blaCMY Genes in Escherichia coli and Salmonella Isolated from Food Animals and Ground Meat. 2001. Antimicrob. Agents Chemother. 45: 3647-3650.

Dr. Silvers is a Veterinary Medical Officer in CVM's Division of Epidemiology. Dr. Spires is an Epidemiologist in CVM's Division of Epidemiology.