Index

A

Accountability for drug use, 4, 5, 6, 27, 46, 62, 81, 98-99, 174, 178

Administration regimens.

See also Subtherapeutic antibiotic use

and antibiotic resistance, 31, 33, 72, 151, 163-164

combinations of drugs, 160, 163-164, 197

gradient approach, 72, 157-158

in rotation, 31, 33, 72, 160

routes, 34-37, 82, 83, 85, 103

subtherapeutic doses, 71-72, 151

therapeutic doses, 157, 158

Aerococcus viridans, 59

Aeromonas spp., 130-131

A. hydrophila, 127, 128-129, 132-135

A. liquefaciens, 59

A. salmonicida, 59

Agalactia, 43

AGRICOLA, 14

Agricultural Marketing Service, 110-111

Agricultural Research Service, 89, 139, 174, 190

Alabama, 30

Allergenicity of antibiotics, 6, 69, 82, 84-85, 144

American Feed Industry Association, 13

American Sheep Industry Association, 60

American Veal Association, 60

American Veterinary Medical Association, 13, 63-64

Amoxicillin, 42, 45, 52, 54

Ampicillin, 42, 52, 54, 146, 162, 164, 165, 166, 167, 172

Amprolium, 32, 33, 57

Anaplasmosis, 44, 50

Animal and Plant Health Inspection Service (APHIS), 139, 162, 174, 190

Animal Drug Availability Act (ADAA), 6, 10, 99-100, 107

Animal health industry, economics of subtherapeutic drug use, 180, 186

Animal Health Institute (AHI), 81, 148, 149, 171

Animal management practices

and antibiotic resistance, 9, 150-153, 159, 160

aquaculture, 58, 206

beef cattle, 50, 67, 191, 206

behavioral stress, 193

biosecurity techniques, 197-199

dairy cattle, 44, 64-65, 191-192, 197, 199, 201, 203-205

fly control, 50, 199

heat stress management, 190-193

immune-function enhancers, 200-202

intensive management and confinement operations, 31



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The Use of Drugs in Food Animals: Benefits and Risks Index A Accountability for drug use, 4, 5, 6, 27, 46, 62, 81, 98-99, 174, 178 Administration regimens. See also Subtherapeutic antibiotic use and antibiotic resistance, 31, 33, 72, 151, 163-164 combinations of drugs, 160, 163-164, 197 gradient approach, 72, 157-158 in rotation, 31, 33, 72, 160 routes, 34-37, 82, 83, 85, 103 subtherapeutic doses, 71-72, 151 therapeutic doses, 157, 158 Aerococcus viridans, 59 Aeromonas spp., 130-131 A. hydrophila, 127, 128-129, 132-135 A. liquefaciens, 59 A. salmonicida, 59 Agalactia, 43 AGRICOLA, 14 Agricultural Marketing Service, 110-111 Agricultural Research Service, 89, 139, 174, 190 Alabama, 30 Allergenicity of antibiotics, 6, 69, 82, 84-85, 144 American Feed Industry Association, 13 American Sheep Industry Association, 60 American Veal Association, 60 American Veterinary Medical Association, 13, 63-64 Amoxicillin, 42, 45, 52, 54 Ampicillin, 42, 52, 54, 146, 162, 164, 165, 166, 167, 172 Amprolium, 32, 33, 57 Anaplasmosis, 44, 50 Animal and Plant Health Inspection Service (APHIS), 139, 162, 174, 190 Animal Drug Availability Act (ADAA), 6, 10, 99-100, 107 Animal health industry, economics of subtherapeutic drug use, 180, 186 Animal Health Institute (AHI), 81, 148, 149, 171 Animal management practices and antibiotic resistance, 9, 150-153, 159, 160 aquaculture, 58, 206 beef cattle, 50, 67, 191, 206 behavioral stress, 193 biosecurity techniques, 197-199 dairy cattle, 44, 64-65, 191-192, 197, 199, 201, 203-205 fly control, 50, 199 heat stress management, 190-193 immune-function enhancers, 200-202 intensive management and confinement operations, 31

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The Use of Drugs in Food Animals: Benefits and Risks moisture management, 39, 199-200 nutrition, 50, 192, 202-206 overcrowding, 193 pasture management, 50 poultry, 61, 191, 192-193 probiotics (direct-fed microbial), 195-197 recommendations, 11, 208-209 sheep, 54-55 subtherapeutic drug-use alternatives, 181, 182, 189-190 swine, 41, 181, 191, 197-198, 206 vaccination, 193-195 Animal Medicinal Drug Use Clarification Act (AMDUCA), 5, 10, 97-99, 107 Anthelmintic, 54, 55-56, 82 Antibiotic drug use. See also Ban on subtherapeutic antibiotic use; Subtherapeutic antibiotic use animal management alternatives to, 9, 190-202 applications, 2, 4, 19, 28, 71 for aquaculture, 59 for beef cattle, 52, 175 benefits, 1-2, 4, 13, 21, 25, 29, 68, 72, 73-75, 107, 174-175 case studies, 166-176 concerns, 15, 24, 25-26, 142-143, 155 in dairy industry, 45, 46, 47-48, 52, 119-120 disease eradication and, 190, 206 genetics and, 207-208 growth promotion with, 28, 31, 34, 51-53, 81, 153-154 hazards (potential), 6, 75-81 history, 20-22, 153-154 illegal, 182 issues, 19-26 literature review, 3, 14, 15-19 magnitude of, 24-25 for minor species, 56, 57 multidrug therapy, 147-148 nutrition and, 202-206 in poultry industry, 18, 32, 175 recommendations, 10, 177-178 in sheep industry, 55 in swine industry, 41-42, 175 therapeutic, 13, 28, 72-73, 103, 153-161 trends, 25 in veal industry, 53, 54 Antibiotic drugs. See also specific drug allergenicity in humans, 6, 69, 82, 84-85, 144 availability concerns, 4, 7, 10, 24, 81, 107, 143, 148-149, 176-177 bactericidal, 147-148 bacteriostatic, 147-148 banned, 77, 78, 83-84, 97, 101-102 cell division targets, 147 defensins, 147 DNA gyrase inhibitors, 147 endotoxin blockers, 146 human last line of defense, 35, 168-169, 175 identifying and screening new drugs, 145-148 mechanisms of action, 28, 143-145, 154-155 metabolism modifiers administered with, 146 nonsystemic, 82 over-the-counter availability, 4, 6, 46, 65, 81, 182, 186 protein secreton inhibitors, 147 protein synthesis inhibitors, 146-147 residues in foods, 14, 21, 63, 116-117, 118 synthetic, 146, 163, 168 systemic, 82 toxicity to humans, 6, 77, 81-82, 83-84, 144 Antibiotic resistance administration regimen and, 31, 33, 72, 151, 160, 162, 163-164 animal management practices and, 150-153, 159 age of animal population and, 166 assessment methods, 8-9, 170 and availability of drugs, 4, 7, 9, 24, 81, 107, 143, 148-149, 168-169 causes, 69, 70, 81, 86 cross-genera transfer, 152-153 cross-resistance, 178 data availability, 69, 70, 73 definition of, 7-8, 21, 166, 170, 171, 176 development and transmission, 7, 76-77, 78, 79, 150, 151-153, 155-156, 161, 168, 171, 172, 176 economic factors, 150, 182-183 fluoroquinolone controversy, 166, 168-175, 182-183 food-borne pathogens, 2, 8, 23, 70-71, 86, 87, 138, 140, 155, 166, 168, 171, 172 and human health risk, 2, 4, 7, 9, 13, 21, 22-26, 69, 70, 76-78, 79, 86-87, 138, 143, 150, 155, 160, 161-166, 168, 172

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The Use of Drugs in Food Animals: Benefits and Risks literature review, 3, 22 mechanisms of action, 146, 151, 154-155, 169 multidrug, 21, 23-24, 78, 79, 80, 107, 138, 149, 152, 153, 154, 159, 162, 170, 176, 183 nonpathogenic bacteria, 8-9, 176, 196 plasmid transfer, 22, 152-153, 169 productivity effects, 43 recommendations, 10, 177-178 regulatory and approval process and, 7, 9, 166, 168-176 reservoirs of bacteria, 79, 80, 87, 153, 155, 159, 160, 161, 166, 168, 169, 172 selection pressures, 77, 150, 154, 169, 176 sentinel organisms, 172, 174, 177 Subtherapeutic drug use and, 7, 18, 79, 81, 150, 151, 154, 156, 160 therapeutic doses and, 7, 72-73, 79, 150-151, 156, 158, 160-161, 169, 176 tracking emergence of, 7, 10, 70, 140, 157, 160, 162-166, 168, 172, 173-174, 176, 177 trends, 78-81, 161-166, 183, 196 vancomycin-like, 18, 22, 152-153 veterinary clinical implications, 161-166, 176-177 virginiamycin controversy, 175-176 Antioxidant therapy, 202-206 Antiparasitic drugs, 2, 14, 41-42, 45, 51, 58 Antiprotozoal compounds, 31, 33, 59, 82 Antiseptics, topical literature, 14 uses, 1, 12 AOAC INTERNATIONAL, 112, 125, 126 Apramycin, 42, 164, 165, 167 Aquaculture industry compassionate INADs, 94 drug use in, 2, 13, 58-60, 94, 101, 119, 149. See also Fish and shellfish growth and structure, 56-58 management strategies, 58, 206 quality assurance, 58 residues in fish and shellfish, 119 Arcobacter spp., 127, 128-129 Arizona, 192 Arkansas, 30 Arsanilate, 32 Arsanilate sodium, 43 Arsenical compounds, 14, 31, 33, 34, 38, 116-117, 118 Arsenilic acid, 42, 43 Association of American Feed Control Officials, 197 Atrophic rhinitis, 43 Avian influenza, 31, 33, 61, 206 Avian leukosis, 207 Avoparcin, 18, 79, 166, 168, 171 Azithromycin, 170 B Bacillus cereus, 128-131, 134-135 Bacitracin, 21, 32, 38, 39, 42, 52, 57, 75, 82 Bacterial hemorrhagic septicemia, 59 Bacterial infections categories of, 71 stress and, 71 Bactericides, uses, 2, 12 Bambermycin, 32, 42, 82 Ban on subtherapeutic antibiotic use consumer costs, 181-182, 183-184 economics analysis, 180-186 effect of, 15, 18, 180-184 extra-label, 107 fluoroquinolones, 107 and management practices, 181, 182 measurement of costs, 180-182 petitions for, 156-157 recommendations, 15 total vs. partial, 182-183 Banned drugs, 77, 78, 83-84, 97, 101-102 Beef cattle production. See also Meat and antibiotic resistance, 162, 167, 169 breeding programs, 207 disease prevention, 50, 51-53, 159, 175, 180 economics, 25, 51, 180, 181, 182, 184, 185, 187 growth promotion, 50, 51, 53, 56, 154 history and growth, 48-49, 102 management strategies, 50, 67, 191, 206 microbiological hazards, 75, 130-131 quality assurance program, 67-68 residues in slaughtered animals, 83 specialty producers, 181 structure of industry, 30, 49 therapeutic drug use, 51-53, 74, 180, 182 trends in drug use, 25, 50-51 vaccinations, 50, 53 Beef Quality Assurance program, 67-68

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The Use of Drugs in Food Animals: Benefits and Risks Behavioral stress, management of, 193 Beta-carotene, 204-205 Beta-lactam antibiotic residues, 84, 119, 120, 123, 143, 144. See also Penicillin Biosecurity measures, 35, 159, 197-199 BIOSIS, 14 Bison, 56 Blackhead, 33 Bloat, 2, 13 Bluetongue, 50, 55 Bodo spp., 59 Bordetella spp., 194 B. avium, 31 B. pertussis, 194 Bovine leukocyte adhesion deficiency, 207 Bovine lingual antimicrobial peptide, 147 Bovine lymphocyte antigen, 207-208 Bovine respiratory syncytial virus, 45 Bovine somatotropin, 2, 13, 48 Bovine viral diarrhea, 45 Breeding, 40, 44, 47, 48, 49 for disease resistance, 35, 206-208 Brucella spp., 127 B. melitensis, 136 Brucellosis, 45, 50, 53, 72, 136, 190, 206 Buquinolate, 32 C California, 54, 98, 136, 191 Campylobacter spp. antibiotic-resistant, 159-160, 166, 170, 171, 172, 196 C. coli, 127 C. fetus, 74 C. jejuni, 23, 127, 130-135, 197 food-borne illness in humans, 86, 127-135, 137 vaccination against, 194 Campylobacteriosis, 23 Canada, 104-105, 164, 165 Carbadox, 43 Carbenicillin, 162 Carcinogenic compounds, 6, 33, 82, 84, 102 Catfish Farmers of America, 60 Ceftiofur, 25, 52 Ceftiofur sodium, 34 Center for Drug Evaluation and Research, 174 Center for Food Safety and Applied Nutrition, 174 Center for Veterinary Medicine, FDA, 2, 13, 33, 88. See also Regulatory and approval process criticisms of policies of, 95-96 extra-label use policy, 5, 96-99, 142 Office of New Animal Drug Evaluation, 89 Office of Surveillance and Compliance, 89 organizational structure, 5, 89, 90 practices and procedures, 91-92, 100, 107 residue monitoring, 112-113, 114, 123, 126 responsibilities, 5, 10, 89, 112, 173-174, 197 trends in drug approvals, 94, 101, 169 Centers for Disease Control and Prevention, 22, 85-86, 88, 127, 130, 133, 139, 140, 170, 174 Cephalosporins, 77, 161, 162 Cephalothin, 162, 165 Cephapirin, 45 Chemical residues in animals, 58, 61, 161 Chemotherapeutic compounds, 43 Chickens. See Poultry Chilodonella spp., 59 Chloramphenicol, 77, 78, 83-84, 97, 119, 120, 162, 163, 164, 165, 166, 167, 172 Chlortetracycline, 21, 32, 42, 52, 55, 57, 75, 154, 158 Cholera, 31, 41, 190 Chromium, 205-206 Ciprofloxacin, 169, 170, 172-173 Classes of food-animal drugs, 2, 12 Clean Water Act, 139 Cleidodiscus spp., 59 Clenbuterol, 116-117, 118 Clinton administration, 91-92, 100, 138-139, 195-196 Clopindol, 32 Clostridium spp. in beef cattle, 50, 53, 130-131 C. botulinum, 128-129 C. perfringens, 39, 40, 43, 55, 128-135 in poultry, 39-40, 134-135 resistant strains, 39-40 in sheep, 55, 132-133 in swine, 43, 128-129 vaccination against, 194 Cloxacillin, 45 Coccidia, resistant, 31, 33 Coccidiosis, 31, 39, 44, 54, 56 Coccidiostats, 31, 32, 33, 34, 38, 39, 45, 51, 56, 57, 82

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The Use of Drugs in Food Animals: Benefits and Risks Codex Alimentarius Commission, 114 Codex Committee on Residues of Veterinary Drugs in Foods, 106 Colemon Natural Beef, 181 Colibacillosis, 55 Coliform plasmid transfer, 22 Colisepticemia, 72 Colony stimulating factors, 200-202 Colorado, 54 Committee on Drug Use in Food Animals charge to, 2, 13-14 process, 3 Competitive exclusion products, 39, 196-197 Compliance Policy Guides, 63 Consumer concerns, 13, 21-22, 69 costs of ban on subtherapeutic antibiotic use, 181-182, 183-184 education, 175, 178 Continuing education programs, 67 Copper, 205, 206 Corynebacterium bovis, 204 Cost of medications, 31, 35, 36-37, 51 Costia spp., 59 Council on Agriculture and Science Technology (CAST) report, 15, 16, 18, 21, 75, 160, 182 Coxiella burnetti, 127 Cryptosporidium parvum, 127 Culicoid control, 50 Cysticercus spp., 127 Cytidine monophosphate-KDO synthetase, 146 Cytokines, 29, 195, 200, 202 D Dactylogyrus spp., 59 Dairy industry. See also Drug residues in milk antibiotic drug use, 45, 46, 47-48, 52, 119-120, 162 breeding programs, 208 disease control, 44, 45-47, 52, 162, 191, 197 economics, 25, 45-46 food-borne pathogens from, 75 heat stress management, 191-192 history and growth of, 44, 102 human health risks, 46-47, 162-163 integration of, 30, 44 management strategies, 44, 64-65, 191-192, 197, 199, 201, 203-205 production enhancers, 2, 13, 48, 52, 205-206 prophylactic treatments, 45, 197 quality assurance program, 46, 63-67, 119, 122 therapeutic treatments, 45-47, 51-53 Databases, 14, 67, 98, 99, 120, 140, 176, 177 Decoquinate, 54, 57 Delaney Clause, 102 Denmark, 168 Dequinate, 32 Development of new drugs. See also Regulatory and approval process approval process and, 5, 9-10, 91, 96, 99-100, 101-103, 106-109, 114, 143, 149, 166 ban on subtherapeutic antibiotics and, 186 corporations, number of, 101 costs, 96, 99, 101, 103, 106-107, 149 efficacy requirements, 5, 94, 95, 99-100, 103, 104, 108, 175 environmental evaluation, 96, 101, 175 field trials, 94-95, 99-100, 108 food safety requirements, 83, 100-103, 104, 114 identifying and screening new compounds, 145-148 incentives for, 9, 175 length of time for, 91-92, 103 for minor species, 101 recommendations, 10, 177, 178 target-animal safety studies, 95, 103, 104 Diarrhea, 50, 52. See also Scours Diethylstilbestrol, 82, 97, 102 Dihydroseptomycin, 52 Dimetridazole, 97 Direct-fed microbial products, 195-197 Disease control. See also Therapeutic drug use; Subtherapeutic drug use; Vaccination in beef cattle, 50, 51-53 breeding programs, 207-208 culling, 47-48, 206 in dairy industry, 44, 45-47, 52, 162 eradication programs, 55, 60-61, 190, 206 in poultry, 31-33, 34, 38-40, 60-61, 158-159, 169-170, 171-172, 175, 180, 206 prophylactic treatments, 45 in sheep, 55-56 spontaneous recovery, 47, 48 in swine, 41-42, 43, 74, 75, 158-159, 163, 175, 180, 190, 206 Drug Importation Act, 88

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The Use of Drugs in Food Animals: Benefits and Risks Drug residues in foods. See also Drug residues in milk action levels, 114 administration route and, 82, 85, 103 anabolic compounds, 50 analytical methods, 111-112, 113-115, 119, 123, 140, 141 carcinogenic, 82 Compound Evaluation System, 116 defined, 112 exposure potential, 113, 116 in fish and seafood, 58, 119, 140 foreign standards, 104-105 human health risks from, 6, 50, 81-86, 87, 100-103, 116 maximum residue levels, 82, 114 in meat and poultry, 33, 41, 51, 83, 115-119 microbial contamination risks compared, 85-86, 87 monitoring and enforcement, 67, 84, 111, 113-114, 115-119, 123, 140, 141 pharmacokinetics in diseased animals and, 140-141 recommendations, 141 regulatory and approval process, 82, 100-103, 107, 110-111, 114-115 risk assessment, 100-103, 116, 117 safe levels, 114 screening, 6, 65-66, 111-112 surveillance testing, 115-116, 123-124, 140 standard setting, 84, 105-106, 108-109, 111-113 target tissue sites, 113-114, 117 tolerance levels, 104-105, 108, 111, 114, 117, 119 toxicity, 81-82, 103, 112-113 tracking, 41, 113-115 violations, 83, 115, 116-117, 118, 183 Drug residues in milk analytical methods, 119, 122, 124-126 controversies, 125-126 database program, 120 monitoring and enforcement, 120, 124-125 Pasteurized Milk Ordinance, 63, 64, 66, 119, 121-122, 123, 125, 126 testing for, 65-66, 122-124, 125-126 tracking, 46 violation rates, 120-121 Duck, 57 Dysentery, 75 Dystocia, 44 E Echinococcus multilocularis, 194 Economics issues antibiotic resistance, 150 cost of medications, 31, 35, 36-37, 51 drug development costs, 96, 99, 101-103, 106-107, 149 food-animal production, 1, 4, 21, 24-25, 75 food-borne illnesses, 38, 138 subtherapeutic drug use, 179-187 testing for residues, 125 Economic Research Service, USDA, 13 Ectoparasites, 31, 50 Edwardsiella ictaluri, 59 Efrotomycin, 25, 42 Egg Products Inspection Act, 111 Eimeria, 39, 194 Endectocides, 51 Endotoxins, 146 Enforcement of regulations product labeling, 96-97 recommendations, 141 residues in foods, 115 responsibility for, 84 Enteric septicemia, 59, 73 Enteritis, 44, 54, 57, 127, 164, 165 Enterococcus spp., 74, 79, 152-153 Enterotoxemia, 47, 55 Enzootic abortion, 55 Epididymitis, 55 Epistylis spp., 59 Erysipelas, 31, 41, 43 Erysipelothrix rhusiopatheae, 75, 128-129, 194 Erythromycin, 32, 42, 45, 52, 55, 75, 82, 160, 162 Escherichia coli in cattle, 130-131, 193, 201 compounds available for treating infections, 35, 163-164 drug-resistant, 22, 39, 153, 155, 156, 159, 163-164, 165, 166, 169, 174, 196 enterotoxigenic, 196 immune function mediators and, 201 in meat and meat products, 128-133 monitoring, 140 nonpathogenic, in gut flora, 39 nutrition and, 203 O157:H7 strain, 72, 74, 127, 128-135, 138, 155, 193, 194 in poultry, 35, 39, 134-135, 153, 194, 196 scours, 43

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The Use of Drugs in Food Animals: Benefits and Risks in swine, 43, 128-129, 194 vaccinations, 193, 194 Estradiol, 53 Estradiol/progesterone, 53 Estradiol/testosterone, 53 Estrus synchronizers, 51, 55 European Economic Community, 104, 105, 106 Extra-label use of drugs, 5, 10, 67, 92, 96-99, 107, 140, 142 F Farm Bill of 1990, 13 Federal Food, Drug, and Cosmetic Act, 5, 88, 93, 96, 111 Food Additives Amendment, 102 n.2 Federal Insecticide, Fungicide, and Rodenticide Act, 111 Federal Meat Inspection Act (FMIA), 111 Federal Security Agency, 88 Feed poultry, 34 Fish and shellfish, drug residues in, 119, 140 Florida, 98, 192 Fluoroquinolones, 25, 32, 35, 107, 160, 166, 168-175, 182-183 Fly control, 50, 55 Food and Agriculture Organization, 106 Food and Drug Administration (FDA), 73, 130. See also Center for Veterinary Medicine Bureau of Veterinary Medicine, 89, 96 Compliance Policy Guides, 63 food safety responsibilities, 138, 139, 140 Grade A Pasteurized Milk Ordinance, 63, 64, 66, 121-122 history, 88 milk safety program, 119, 120, 123 monitoring activities, 5, 85-86, 115, 119 Office of Seafood, 119 Officer of the Commissioner, 174 quinolone policy, 170 residue standard setting and enforcement, 84, 99, 111 Food Animal Residual Avoidance Databank (FARAD) project, 5, 67, 98, 99 Foodborne Diseases Active Surveillance Network, 140 Food-borne pathogens, 126-127. See also Microbial contamination of food antibiotic resistance in, 8, 70-71, 86, 87, 138, 140, 171 determination of, 71, 127-133 hazardous organisms, 73-74, 75, 126-127 outbreaks of illness, 22-23, 25-26, 85-86, 122, 133, 136-137, 146, 155, 172 selection of, 80 sentinel organisms, 127, 136-137, 172 surveillance barriers, 71 Food handling, 7, 8, 139, 172 FoodNet, 140 Food poisoning. See Food-borne pathogens Food safety, responsibility for, 98, 139, 195-196 Food Safety and Quality national initiative, 98 Food Safety Inspection Service (FSIS), 5, 63, 83, 85, 86, 88, 111, 112, 113, 115, 116, 117, 127, 130, 141, 174 Foot-and-mouth disease, 50 Foot rot, 44 Formalin, 59, 94 France, 164, 165, 166 Fungi, 31 Fungicides, 2, 12, 33, 59 Furamazone, 52 Furazolidone, 33, 165, 167 Furunculosis, 59 G Gaffkemia, 59 Gastroenteritis, 43 Gastrointestinal diseases, 50 Geese, 56 Genetic selection strategies, 35, 207-208 Gentamycin, 32, 42, 52, 83, 162, 165, 169 Gentamycin sulfate, 34 Georgia, 30 Germany, 38, 166, 169, 170 Goats, 56, 57, 83, 101, 102, 149 Gonadotropins, 55 Good laboratory practice (GLP) regulations, 89, 95 Grade A Pasteurized Milk Ordinance (PMO), 63, 64, 66, 119, 121-122, 123, 125 Gram-negative bacteria, 146 Growth promotion and feed efficiency with antibiotics, 28, 31, 34, 51-53, 81, 153-154 in beef cattle, 50, 51-53, 56, 154 in dairy cattle, 52 in minor species, 57 in poultry, 31, 34, 38, 56, 154

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The Use of Drugs in Food Animals: Benefits and Risks in sheep, 55-56 with steriodal and nonsteroidal estrogenic agents, 29, 31 in swine, 42-43, 154 Grub control, 57 Guidelines definition, 95-96 dosage, 10 testing, 100, 108, 123, 126 Gyrodactylus spp., 59 H Halofuginone, 116-117, 118 Hazard Analysis and Critical Control Points, 62, 68, 137, 139 Heat stress management, 190-193 Helminth control, 42 Hemophilus piscium, 59 Hemophilus pleuropneumonia, 43 Hemorrhagic enteritis, 31 Hetacillin, 45 Hill Farm Research Station, 199 Histomonas influenza, 155 Histomoniasis, in poultry, 33 Hospital-acquired (nosocomial) bacterial infections, 22, 24, 69 Human health risks animal-to-human transfer of disease, 78, 79, 80, 86-87, 143, 161-162, 168, 171, 172 antibiotic resistance and, 2, 4, 7, 9, 13, 21, 22-26, 69, 70, 76-78, 79, 86-87, 138, 150, 154-155, 160, 161-166, 168, 172 carcinogens, 82 cases of disease, 3, 22-23 from dairy cattle, 46-47 hospital-acquired infections compared, 22, 24, 69 magnitude of threat, 2, 3, 9, 23-24, 70, 77-78, 86 manure exposure and, 79, 87 mathematical model, 18 from poultry, 38-40 regulatory and approval process and, 100-103 from residues in food, 81-86, 100-103, 116 sensitive populations, 8, 9, 25-26, 70 steroid growth promoters, 50 of subtherapeutic antibiotic use in animals, 18, 75, 76, 150, 160 toxicity of antibiotics, 6, 77, 81-82, 83-84 I Icthyopthirius spp., 59 Identification of treated animals, 65 Immunostimulants, 200-202 Imported foods, 140 Infectious bovine rhinotracheitis, 45, 53 Influenza, 31, 33 Injection site tissue damage, 67 Insecticides and insecticidal ear tags, 51 Inspection at slaughter, 75 Institute of Medicine (IOM), 15, 17, 18, 150, 156 International Conference on Harmonization, 104 International Meeting on Nucleic Acid Vaccines for Prevention of Infectious Diseases, 195 Ionophores, 2, 12 antiprotozoals, 33 coccidiostats, 31, 32, 33 for growth promotion, 50, 56 Iowa, 40 Ipronidazole, 33, 97 Irradiation of food, 71, 175 Iron, 206 Israel, 192 Ivermectin, 57, 116-117, 118 J Japan, 104, 105 Joint Expert Committee on Food Additives, 106 K Kanamycin, 162, 165 L Labels/labeling, drug, 65, 67, 96, 100 Lactobacillus spp., 39-40, 196 Laminitis, 44 Lasalocid, 32, 52, 56 Leptospira interrogans, 127 Leptospirosis, 43, 45, 53, 72, 74 Levamisole, 116-117, 118 Lice, 43 Lincoln, Abraham, 88

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The Use of Drugs in Food Animals: Benefits and Risks Lincomycin, 38, 39, 42, 82, 162 Lincosaminides, 160 Listeria spp., 127 L. monocytogenes, 75, 128-135 Literature review databases, 14 major reports, 3, 15-19, 22 Litter, water activity of, 39 Liver abscesses, 50, 75, 180 Louisiana State University, 199 Lyme disease, 70 M Maduramycin, 32 Manure, environmental exposure to, 79, 80, 159, 161, 166 Marek’s disease, 31, 34, 207 Mange, 43, 55 Mastitis, 43, 44, 45, 46, 47, 52, 162, 191-192, 199-200, 201, 203-205, 208 Meat bacterial contamination, 74, 75, 127-137 drug residues in, 47, 63, 64, 83, 85, 113, 115-119 inspection, 111 Melengestrol, 53 Methicillin, 162 Metritis, 43, 44, 45, 205 Microbial contamination of food. See also Food-borne pathogens; specific pathogens costs of, 138 illness determinants, 131-133 magnitude and severity of threat, 69, 86, 87, 137-138 meat and meat products, 127-136, 141 milk and other dairy products, 121-122, 133, 136 poultry, 35, 38-40, 75, 134-135 prevention, 71, 195-196 recommendations, 141 residue risks compared, 85-86, 87 risk assessment, 140 routes of, 127 surveillance and monitoring of, 85-86, 138, 139, 140, 141 Milk. See also Drug residues in milk pathogen contamination, 121-122, 133, 136, 163-164 Milk and Dairy Beef Quality Assurance Program, 63 Milk and Dairy Beef Residue Prevention Protocol, 63, 66, 123 Minnesota, 137 Minor species. See also individual species drug use in, 5, 56, 57, 149 veal calves as, 54 Mite control, 55 Moisture management, 39, 199-200 Monensin, 32, 52, 57 Monitoring antibiotic resistance in pathogens, 7, 70, 140, 157, 160, 162-166, 168, 174, 176 disease outbreaks, 85-86 drug residues in food, 5, 6, 34, 71, 86, 113-114, 115, 124-125, 140 microbial contamination, 86 Monogenetic trematodes, 59 Montana, 54 Morantel tartrate, 118 Morocco, 39 Mosquito control, 50 Mutagens, 6, 82, 84 Mycobacterium spp., 127, 194 Mycoplasma spp., 194 M. galisepticum, 33, 60 M. meleagridis, 60 M. synovia, 33, 60 N Nalidixic acid, 165, 168, 169, 173 Narasin, 32 National Antimicrobial Monitoring System, 174 National Antimicrobial Susceptibility Monitoring Program, 140 National Aquaculture Association, 60 National Broiler Council, 60, 61 National Cattlemen’s Association, 51 National Cattlemen’s Beef Association, 60, 67 National Committee for Clinical Laboratory Standards (NCCLS), 170, 171 National Conference on Interstate Milk Shipments (NCIMS), 119, 120, 123, 125 National Drug Residue Milk Monitoring Program, 120 National Food Safety Initiative, 139-140

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The Use of Drugs in Food Animals: Benefits and Risks National Institutes of Health (NIH), 195 National Mastitis Council, 125 National Milk Producers Federation, 60, 63-64 National Pork Producers Council (NPPC), 60, 61, 62, 63 National Poultry Improvement Plan, 60-61 National Research Council, 2, 13, 16, 205 National Residue Program, 115 National Surveillance for Antibiotic Resistance in Zoonotic Enteric Pathogens, 174 National Turkey Federation, 60 Chemical Residue Avoidance Program, 61 National Turkey Improvement Plan, 60 National Veterinary Services Laboratory, 162 Necrotic enteritis, 39 Nematode control, 45 Neomycin, 32, 42, 52, 55, 57, 82, 83, 162, 164, 165, 166, 167 Nequinate, 32 Netherlands, 166, 170, 171 Newcastle disease, 31, 61 Nicarbazin, 32 Nitrarsone, 33 Nitrofurans, 25, 33, 35, 82, 84, 97, 102, 164 Nitrofurazone, 82, 165 Nitroimidazole, 82, 84, 102 Nonpathogenic bacteria, 8-9, 176 Nonsteroid growth promoters, 14 North Carolina, 30, 40, 98 Nourseotricin, 153 Novobiocin, 32, 45, 57, 82, 162 Nutrition, 11, 30, 50, 192, 202-206 O Office of Science and Technology Policy, 140 Office of Technology Assessment, 22, 76 Oleandomycin, 32, 42, 82 Organochlorine and organophosphate compounds, 14, 116-117, 118 Ormetoprin, 59 Over-the-counter antibiotic sales, 4, 6, 46, 65, 81, 182, 186 Overcrowding, management of, 193 Oxazolidinones, 146 Oxolinic acid, 119 Oxytetracycline, 32, 33, 42, 45, 52, 53, 55, 59, 75, 94, 154 P Parainfluenza type 3, 45, 53 Parvovirus, 43 Pasteurella spp., 194 P. multocida, 35, 39 pneumonia, 43 Pasteurellosis, 169 Pathogens. See also Antibiotic resistance; Food-borne pathogens; Microbial contamination of food; specific pathogens adaptation to environment, 76-77 animal-to-human transfer, 78, 79, 80, 86-87, 143, 161-162 eradication of, 35 Pathogen Reduction Task Force, 85-86, 130 Penicillin, 18, 20, 21, 32, 38, 39, 42, 45, 51-53, 55, 57, 81, 82, 83, 85, 117, 119, 143, 144, 148, 154, 155, 156, 161, 162, 163-164, 166, 169 Pennsylvania, 204 Peptide production enhancers, 2, 13 Pfisteria, 101 Pheasant, 57 Phenothiazine, 57 Pinkeye, 44, 50 Pirlimycin, 45 Poison Control Center, 95 Porcine stress syndrome, 207 Pork Quality Assurance (PQA) program, 61-63 Poultry and poultry products drug residues in, 33, 83, 115-119 microbial contamination, 35, 38-40, 75, 134-135, 168 Poultry production and antibiotic resistance, 18, 32, 153, 158, 162, 167, 168, 169-170, 171-172 breeding programs, 207 Clostridium infections, 39-40 concerns, 35 cost of medications, 35, 36-37 day-old-chick vaccination, 31, 34 disease control, 31-33, 34, 38-40, 60-61, 158-159, 169-170, 171-172, 175, 180, 206 drug approval process, 103 drug use history and trends, 31-34, 35, 169-170 economics of, 25, 30-31, 181, 184, 185, 186-187

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The Use of Drugs in Food Animals: Benefits and Risks Escherichia coli infections, 35, 39, 196 feed and nutrition, 30, 34 growth promotion, 1, 31, 34, 38, 56, 154 history and growth of industry, 29-30, 102 integration of industry, 30-31, 33, 49 management practices, 61, 191, 192-193 quality assurance program, 34, 60-61 routes of drug administration, 34-37 Salmonella infections, 38-39, 158, 162, 167, 197, 206 vaccinations, 31, 33, 40 water medication, 34-35 withdrawal period, 33, 34, 38 Poultry Products Inspection Act (PPIA), 111 Prevention of bacterial infections, 71-72. See also Prophylactic treatments; Subtherapeutic antibiotic use Probiotics, 39-40, 195-197 Production enhancers, in dairy industry, 48 Production of food animals. See also Animal management practices; individual industries intensiveness, 21, 29 size of industry, 101, 102 trends, 27, 29 Productivity effects of antibiotic resistance, 43 Prophylactic use of drugs in beef industry, 50, 180 in dairy industry, 45, 197 immune function mediators, 200 in poultry industry, 31, 33, 34 risk-benefit analysis, 71-72 Propionibacterium acnes, 202 Pseudomonas spp., 59 Pseudorabies, 43 Psoroptis ovis, 199 Pure Food and Drug Act, 88 Q Quail, 57 Quality assurance programs, 27-28 aquaculture, 58 beef, 67-68 certification, 62, 68, 119 dairy, 63-67, 119 Hazard Analysis and Critical Control Points, 62, 68 incentives for participants, 66 objectives and focus, 60, 68 pork, 61-63 poultry, 34, 60-61 record-keeping, 4, 65, 66, 67 residue screening, 112 VCPR and, 5, 28, 54, 56, 64, 67, 97, 98-99 Quinolones, 147, 159-160, 197 Quinoxaline di-N-oxides, 82, 84 R Rabbits, 57 Rabies, 70, 72 Recombinant bovine somatotropin, 2, 13, 48 Recommendations animal management research, 11, 208-209 antibiotic development and use, 10, 177, 178 antibiotic resistance surveillance, 11, 177-178 consumer education, 178 database, 177 food animal identification, 178 monitoring and enforcement, 141 nutrition research, 11, 208-209 regulatory and approval process, 10, 107-109, 177 vaccination research, 11, 209 Records, treatment, 4, 65, 66, 67 Regulations, 89, 94-95, 96, 97, 106 Regulatory and approval process. See also individual statutes and agencies antibiotic resistance and, 166, 168-176 carcinogenic drugs, 82 compassionate INAD, 94 continuing education programs, 67 direct-fed microbial products, 196-197 dispute settlement, 93, 108 drug development perspectives, 5, 91, 96, 99-100, 101-103, 106-109, 114, 143, 149, 166 efficacy requirements, 6, 94, 95, 99-100, 103, 104, 107, 108 enforcement policies, 96-97 environmental evaluation, 96, 101, 104 extra-label usage, 5, 67, 92, 96-99, 107, 140, 142 field trials, 94-95, 99-100, 108 flexibility in, 91, 108 food-safety research program, 96 guidelines for meeting criteria, 95-96 history, 88

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The Use of Drugs in Food Animals: Benefits and Risks human drug application process compared, 95, 97, 103, 104, 107 human health risks and, 82, 100-103 investigational new animal drug (INAD) application, 89-90, 92, 93, 94, 108 IR4 program, 54 length of, 5, 24, 91, 93, 103, 106-107 monitoring activities, 5, 89 New Animal Drug Application (NADA), 89, 92, 93, 114 organizational structure, 88-89, 90 panel approach, 105-106 preapproval process, 89-91, 92-93, 94-95 quality of sponsor applications, 94 recommendations, 10, 107-109, 177 redirected drug use, 95 redundancy in, 95, 103 reforms needed, 95-96, 99, 107-108 residues in foods, 83, 100-103, 104-106, 107, 108-109, 112, 114 restructuring, 5, 9-10, 91-100, 107, 143 socioeconomic and political pressures, 96, 143 target-animal safety studies, 95, 104 trends in approvals, 94, 101-102 worldwide harmonization of, 104-106, 109, 143 Reindeer, 57 Reinfection and cross-infection of animals, 159 Research barriers, 20, 56 Residues. See Drug residues in food Resistance, defined, 77. See also Antibiotic resistance Respiratory disease complex, 50, 53 Respiratory infections, 44, 50, 52, 54, 55 Rifamycin, 77 Robenidine, 32 Rockefeller University, 80 Roosevelt, Theodore, 88 Roxarsone, 32, 33, 43 Rumen foaming, 2, 13 S Sales of animal drugs, 103 Salmonella spp., 127 animal-to-human transfer, 162-163, 171, 172 in cattle, 162, 167, 169 drug-resistant, 22, 23, 136, 150, 156, 158, 159, 162, 163, 164-166, 167, 169, 171, 172-173, 174, 196 DT-104 strain, 23, 72, 73-74, 138, 149, 155, 170, 172-173 in meat and meat products, 128-133, 162 moisture conditions and, 39 monitoring, 140 in poultry and poultry products, 31, 134-135, 158, 162, 167, 193, 194, 206 reservoirs, 155 S. dublin, 136, 164 S. enteritidis, 136, 164, 165, 194, 206 S. gallinarum, 31, 60-61 S. heidelberg, 163 S. javiana, 136 S. newport, 162-163 S. oranienburg, 136 S. pullorum, 31, 60 S. typhimurium, 136, 155, 159, 164-166, 167, 194 in sheep, 167 in swine, 162, 167 vaccinations, 193 virulence and pathogenicity, 38, 72, 73-74, 138, 150, 155, 159, 196 Salmonellosis economic impacts, 38 in humans, 23, 38, 70, 73-74, 78, 81, 86, 136 in poultry, 38-39 in swine, 74 Salinomycin, 32 Sanitation, 61, 63 satA-gene-mediated streptogramines, 79 Scours, 43, 44 Screening for drug residues in food, 6, 65-66, 111-112, 145-148 analytical approaches, 111-112 confirmatory methods, 112 Screwworm control, 55 Scyphidia spp., 59 Selection pressures, 77, 150, 154, 169, 176 Selenium, 203, 204, 205, 206 Sentinel Site Study, 86, 130 Septicemia, 146 Sheep production antibiotic resistance, 167 disease control, 55-56 drug use in, 55-56, 101, 149 economics, 25 growth of industry, 54, 102 management strategies, 54-55 microbiological hazards, 75, 132-133 residues in slaughtered animals, 83

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The Use of Drugs in Food Animals: Benefits and Risks Shigella sp., 86, 127, 130 Shipping fever, 55 Slaughtered animals residues in, 83 test subjects, 90 South Dakota, 54 Spain, 171 Specific-pathogen-free stock, 35, 206 Spectinomycin, 32, 42 Squab, 56 Staphylococcus spp. multidrug resistant, 153 S. aureus, 35, 46-47, 128-131, 134-135, 201, 203, 205 Sterile packaging, 71, 175 Steroid anabolic growth promoters, 2, 12-13, 14, 50, 53 Storage of drugs, 65 Streptococcus antibiotic resistance, 162 infections, 43 S. agalactiae, 162 S. faecalis, 196 S. suis, 74 Streptomycin, 21, 32, 42, 45, 52, 55, 57, 82, 144, 158-159, 162, 163-164, 165, 166, 172 Streptothricin, 153 Stress, and bacterial infection, 71, 159, 180, 202 Subtherapeutic antibiotic use. see also Ban on subtherapeutic antibiotic use administration strategies, 71-72, 151, 157 and antibiotic resistance, 7, 18, 79, 81, 150, 151, 154, 156, 179 criticisms of, 156 definition of, 4, 15, 28, 180 economic analysis, 107, 179-187 human health risks, 18, 75, 76, 150, 160 importance, 68, 154, 157 low therapeutic dose distinguished from, 51 mechanism of action, 77, 154, 157 substitutes for, 182, 189-190 swine, 41, 42-43 trends, 25 uses, 4, 28, 42-43, 68 Sulfa drugs, 14, 81, 94, 120, 145-146, 148, 160 Sulfabromomethazine, 52 Sulfacetamide, 84 Sulfachloropyrazine, 32, 43, 52, 84 Sulfadimethoxine, 52, 84, 120 Sulfaethoxypyridazine, 43, 52 Sulfamethazine, 32, 43, 50, 52, 63, 84 Sulfamethoxazole, 78, 163-164, 165, 166 Sulfamethoxine, 32, 52, 59 Sulfamyxin, 32 Sulfanilamide, 84 Sulfanitran, 32 Sulfaquinoxaline, 32, 57, 84 Sulfathiazole, 43, 84 Sulfonamides, 32, 33, 51, 52, 54, 55, 84, 116-117, 118, 165, 172 Surveillance testing, drug residues in foods, 115-116, 123-124, 140 Surveys of food-borne illness, 133-137 Swann Committee Report, 15, 16, 156 Sweden, 166 Swine production. See also Pork antibiotic resistance, 43, 158-159, 160-161, 162, 163, 167, 168 breeding programs, 207 disease control, 41-42, 43, 74, 75, 158-159, 163, 175, 180, 190, 206 economics, 25, 40, 75, 181, 182, 185, 186, 187 growth and metabolic performance, 42-43, 154 integration of industry, 30, 40-41, 49 management systems, 41, 181, 191, 197-198, 206 microbiological hazards, 128-129 residues in slaughtered animals, 83, 85 size of industry, 40, 102 slaughter rejection, 75, 76 therapeutic drug use, 182 T Testing feed quality, 61 Testing for drug residues analytical methods, 111-112, 113-115, 119, 123, 140 in milk, 122-124, 125-126 toxicity, 112-113 unresolved issues, 125-126 Tetracycline, 18, 21, 32, 38, 42, 50, 51-53, 78, 81, 82, 83, 120, 152-153, 156, 159, 160, 162, 164, 165, 166, 167, 172 Texas, 54, 136 Thailand, 170 Therapeutic drug use administration regimen, 34-35, 157

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The Use of Drugs in Food Animals: Benefits and Risks and antibiotic resistance, 7, 72-73, 79, 150-151, 156, 157, 158-159, 160-161, 176 in beef cattle, 51-53, 180 in dairy cattle, 45-47 definition, 180 economics of, 74 low-dose, 51, 189 minimal inhibitory concentration (MIC), 150-151, 166, 176 in poultry, 34-35 reduction strategies, 188-189 regulation of, 182 risk—benefit assessment, 72-73, 74, 75, 179 Thiabendazole, 57 Tiamulin, 42 Tilmicosin, 52, 160 Tobromycin, 169 Topical drugs, 1, 12, 82 Toxic shock syndrome, 146 Toxic Substances Control Act, 111 Toxicity of food-animal drugs, 81-82, 83-84, 103, 112-113, 144 Toxoplasma gondii, 127 Toxoplasmosis, 72 Tracking antibiotic resistance, 7, 70, 140, 157, 160, 162-166, 168, 174, 176 drug residues in food, 113-115 Trenbolone, 53 Trends in antibiotic resistance, 78-81 in drug use, 31-34, 50-51 Tricaine methanesulfonate, 59 Trichinella spiralis, 127 Trichodina spp., 59 Trimethoprim, 146, 160, 163, 164, 165, 166, 167, 172 Triple sulfonamides, 162, 165 Trypanosomiasis, 207 Tuberculosis, 31, 50, 72, 190, 206 Turkeys. See Poultry Tylosin, 32, 33, 38, 42, 50, 52, 75, 82 U United Egg Producers, 60 United Kingdom, 75, 155, 164, 168, 170, 171, 172 United States and Canada Free Trade Agreement, 104-105 University of California at Davis, 98 University of Florida, 98 U.S. Department of Agriculture, 2 Bureau of Chemistry, 88 Cooperative State Research, Education, and Extension Service, 98, 139 food safety responsibilities, 138, 140, 174 National Agriculture Library, 14 Pathogen Reduction Task Force, 85-86, 130 residue monitoring and enforcement responsibilities, 111, 114-115 Residue Monitoring Program, 67, 83, 84 U.S. Department of Health and Human Services, 88, 90 U.S. Environmental Protection Agency, 88, 111, 139 U.S. Fish and Wildlife Service, 119 U.S. Public Health Service, 88, 90, 119, 121, 122 U.S. Trout Farmers Association, 60 V Vaccinations, 127 beef cattle, 50, 53, 193 dairy cattle, 45, 193 eradication of disease, 206 mutations introduced by, 194 nucleic acid, 195 pathogen targets, 193-194 poultry, 31, 33, 35, 40, 193, 194 research recommendations, 11, 209 sheep, 55 swine, 41, 43, 194 Vancomycin, 18, 22, 79, 152-153, 166, 168 Veal production, 53-54, 101, 102, 163, 181 Veterinarian-client-patient relationship (VCPR), 5, 28, 54, 56, 64, 67, 97, 98-99 Veterinary feed directive drugs, 100 Vibrio spp., 127 Vibriosis, 55 Virginiamycin, 32, 38, 39, 42, 79, 82, 175-176 Vitamin A, 204-205 Vitamin E, 203, 204, 205, 206 W Water medication, 2, 34-35, 58 quality and availability, 192

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The Use of Drugs in Food Animals: Benefits and Risks Withdrawal diets, 34 intervals, 99 times, 33, 38, 67, 83, 84, 90, 96, 97, 99, 113, 117, 126, 161 World Health Organization (WHO), 17, 18, 78, 106 Worms, 31, 33, 43, 50, 55, 56, 57 Wyoming, 54 Y Yersinia spp., 74 Y. enterolitica, 127, 128-131 Z Zeranol, 53, 55-56 Zinc, 205, 206 Zoalene, 32 Zoonotic disease transfer, 8, 18, 69-70, 72, 74, 87, 150-151, 154, 160, 162-163, 176 Zoothamnium spp., 59