Use of antimicrobial agents in Veterinary Medicine in Malaysia Dr Marzuki Bin Zakaria, Department of Veterinary Services, Malaysia
ANTIMICROBIAL USE IN LIVESTOCK PRODUCTION
What are Antibiotics? Are a type of antimicrobial, specifically, antibiotics are, in most cases, compounds produced by a fungus or another microorganism that kill or inhibit the growth of bacteria that cause disease in humans or animals
WHY DO WE NEED ANTIBIOTICS?
Use Patterns Definition Veterinary examples 1. Antimicrobial Growth Promotion - Group administration - in feed - Long duration Administration of an antimicrobial, usually as a feed additive, over a, period of time to growing animals that results in improved physiological performance (i.e. weight gain, feed conversion) Avilamycin, bambermycin, bacitracin, carbadox, chlortetracycline, tylosin dan virginiamycinin cattle, pigs and 2. Prophylaxis (prevention) - Group administration - in feed and water - Intermediate duration ANTIMICROBIAL USE PATTERNS Administration of an antimicrobial to exposed healthy animals considered to be at risk, but prior to onset of disease, and for which no etiologic agent has yet been confirmed by culture or other detection method(s) poultry Prevention of necrotic enteritis in broilers; intramammary dry cow treatment in dairy cattle; medicated milk replacer in calves to prevent diarrhoea 3. Metaphylaxis - Group administration - injection, in feed and water - Short duration 4. Treatment -targeted invidual (s) - injection, in feed and water - Short duration The mass treatment of animal populations currently experiencing any level of disease before the onset of blatant illness Administration of an antimicrobial to an animal, or group of animals, which exhibits frank clinical disease Control of bovine respiratory disease (BRD) in feedlot cattle Colibacillosis in calves, pigs or poultry; BRD, swine respiratory disease
BENEFITS OF ANTIMICROBIAL USE ON ANIMALS 1.Better animal health 2.Better food safety; 3.Assured continuous food production of livestock sources 4.In terms of economy, direct benefits to livestock producers through reduced number of dead / sick animals 5.Containment of the potential for a massive epidemic which could lead to the death of many animals and negatively affect human life.
RISK USING ANTIBIOTICS IN ANIMALS 1. Contributes to bacterial resistance in animals and complicates the treatment of animal diseases caused by antimicrobial resistant bacteria 2. Contributes to bacterial resistance in humans and complicates the treatment of human disease caused by antimicrobial resistance bacteria 3. Residual antibiotics in livestock meat can be a potential hazard and can cause serious illness to people, such as hypersensitivity and allergic reactions
DATA AND INFORMATION REGARDING ANTIMICROBIAL USAGE IN MALAYSIA
AMOUNT SOLD FOR / USED IN ANIMALS BY ANTIMICROBIAL CLASS AND TYPE OF USE IN MALAYSIA (2015) (SOURCE : MAHNIA) Total amount (AGP + Tx use) Amount for( Tx use + prevention) Amount for AGP Antimicrobial class All animal species (kg) All animal species (kg) All animal species (kg) Aminoglycosides 13475 875 12600 Amphenicols 15225 2625 12600 Arsenicals Cephalosporins (all generations) 120 120 0 1-2 gen. cephalosporins 3-4 gen cephalosporins Fluoroquinolones 4615 4615 0 Glycopeptides Glycophospholipids Lincosamides 3120 120 3000 Macrolides 218290 26490 191800 Nitrofurans Orthosomycins 2520 0 2520 Other quinolones 4000 0 4000 Penicillins 66020 4220 61800 Pleuromutilins 14000 0 14000 Polypeptides 98435 875 97560 Quinoxalines Streptogramins 630 0 630 Sulfonamides (including trimethoprim) 18000 0 18000 Tetracyclines 73920 120 73800 Total kg 532370 40060 492310
LIST OF ANTIBIOTICS UNDER LICENCE B HOLDERS FOR USAGE ANIMAL FEED (2017) (SOURCE: NPRA) Aivlosin Kanamycin Sulfadiazine Amikacin Cifloxacin Kitamycin Sulfadimethoxine Amoxicillin Ciprofloxacin Kitasamycin Sulfadimidine Amphotericin B Clarithromycin Lasalocid Sulfamethazine Ampicillin Clindamycin Leucomycin Sulfamethoxazole Anlamycin Cloxacillin Lincomycin Sulfamethoxine Apramycin Colistin Lindomycin Sulfamethoxypyridazine Aureomycin Danofloxacin Marbofloxacin Sulfanilamide Avilamycin Destomycin Methenamine Sulfamonomethoxin Bacitracin Dihydrostreptomycin Minocycline Bambermycin Doxycycline Nalidixic acid Sulfanilamide/ Sulphanilamide Benzyl Penicillin Enoxacin, Neomycin Sulfaquinoxaline Bicozamycin Enramycin, Norfloxacin Sulfathiazole Cefadroxil Enrofloxacin, Ofloxacin Sulfonamides Cefalexin/ Cephalexin Erythromycin Oleandomycin Terramycin Flavomycin Oxolinic acid Tetracycline Cefaloridin Flavophospholipol Oxytetracycline Tetroxoprim Cefalotin/ Cephalothin Florfenicol Penicillin Thiamphenicol Flumequine Phthalylsulfathiazole Tiamulin Cefamandol Polymyxin Tilmicosin Fosfomycin/ Phosphomycin Cefazolin Robenidine Tobramycin Cefotaxim Gentamicin Semduramicin Trimethoprim Cefoxitin Hetacillin Spectinomycin Trimoxazole Ceftiofur Hydromycin B Spiramycin Tylosin, Cefuroxim Hygromycin Streptinomycin Tylvalosin Cephalosporin Isovaleryl Tylosin Streptomycin Valosin Chlorotetracycline/Chlortetracycline Josamycin Sulfachloropyridazine Virginiamycin
TABLE 1. ANTIBIOTICS USAGE IN FEED LISTED UNDER ANTIMICROBIAL CLASS IN MALAYSIA (2017) AMINOGLYCOSIDES & AMINOCYCLITOLS Amikacin Apramycin Destomycin Dihydrostreptomycin Framycetin Gentamicin Hygromycin b Kanamycin Neomycin Netilmycin Paromomycin Spectinomycin Streptomycin Tobramycin AMPHENICOLS Chloramphenicol Florphenicol Thiamphenicol CEPHALOSPORINS Cephalosporins 1 st Gen Cefacetrile Cefalexin (cephalexin) Cefalotin (cephalothin) Cefapyrin Cefazolin (cephazolin) Cefalonium Cefadroxil (cefadroxyl) Cefaloglycin (cephaloglycin) Cefalonium (cephalonium) Cefaloridine (cephaloradine) Cefapirin (cephapirin) Cefatrizine Cefazaflur Cefazedone Cefradine (cephradine) Cefroxadine Ceftezole Cephalosporins 2 nd Gen Cefuroxime Cefaclor Cefamandole Cefmetazole Cefonicid Cefotetan Cefoxitin Cefprozil (cefproxil) Cefuzonam Cephalosporins 4 th Gen Cefclidine Cefepime Cefluprenam Cefoselis Cefozopran Cefpirome Cephalosporins 3 rd Gen Cefoperazone Ceftiofur Ceftriaxonne Cefquinome Cefcapene Cefdaloxime Cefdinir Cefditoren Cefetamet Cefixime Cefmenoxime Cefodizime Cefotaxime Cefpimizole Cefpodoxime Cefteram Ceftibuten Ceftiolene Ceftizoxime Ceftazidime Cephalosporins 5 th Gen Ceftobiprole Ceftaroline Cephalosporins (Not Classified) Cefaclomezine Cefaloram Cefaparole Cefcanel Cefedrolor Cefempidone Cefetrizole Cefivitril Cefmatilen Cefmepidium Cefovecin Cefoxazole Cefrotil Cefsumide Cefuracetime Ceftioxide
TABLE 2. ANTIBIOTICS USAGE IN FEED LISTED UNDER ANTIMICROBIAL CLASS IN MALAYSIA (2017) FLUOROQUINOLONES Danofloxacin Difloxacin Enrofloxacin Marbofloxacin Orbifloxacin Fluoroquinolones 1 st Gen Piromidic acid Pipemidic acid Rosoxacin Fluoroquinolones 2 nd Gen Cifloxacin Ciprofloxacin Enoxacin Lomefloxacin Nadifloxacin Norfloxacin Ofloxacin Pefloxacin Rufloxacin Fluoroquinolones 3 rd Gen Balofloxacin Gatifloxacin Grepafloxacin Levofloxacin Moxifloxacin Pazufloxacin Sparfloxacin Temafloxacin Tosufloxacin Fluoroquinolones 4 th Gen Besifloxacin Clinafloxacin Gemifloxacin Sitafloxacin Trovafloxacin Prulifloxacin Besifloxacin LINCOSAMIDES Clindamycin Lincomycin Pirlimycin ORTHOSOMYCINS Avilamycins OTHER QUINOLONES Flumequine Nalidixic Acid Oxolinic Acid GLYCOPHOSPHOLIPIDS Bambermycin Flavomycin Flavophospholipol PENICILLINS Narrow-spectrum β- Lactamase-sensitive Penicillins Penicillin G (benzylpenicillin) Penicillin V [ phenoxymethyl-penicillin] Phenethicillin Broad-spectrum β- Lactamase sensitive Penicillins with Extended Spectra carboxypenicillins (carbenicillin) carboxypenicillins (ticarcillin) ureido-penicillins (azlocillin) ureido-penicillins ( mezlocillin) piperazine penicillins (piperacillin) Broad-spectrum β- Lactamase-sensitive Penicillins Ampicillin Amoxicillin Hetacillin Pivampicillin Talampicillin Clavulanate-potentiated amoxicillin Mecillinam Narrow-spectrum β- Lactamase resistant Penicillins oxacillin cloxacillin dicloxacillin flucloxacillin Methicillin nafcillin Temocillin Carbapenems Imipenem meropenem
TABLE 3. ANTIBIOTICS USAGE IN FEED LISTED UNDER ANTIMICROBIAL CLASS IN MALAYSIA (2017) MACROLIDES Aivlosin Amphotericin B Clarithromycin Erythromycin Gamithromycin Josamycin Kitamycin Kitasamycin Leucomycin Oleandomycin Spiramycin Tildipirosin Tilmicosin Tulathromycin Tylosin Tylvalosin Isovaleryl Tylosin ANTIPROTOZOALS Robenidine POLYETHERS IONOPHORES Lasalocid Monensin Salinomicin Narasin Maduramicin Theostrepton Semduramicin POLYPEPTIDES Bacitracin Bicozamycin Capreomycin Colistin sulphomethate Enramycin Gramacidin Polymixin B Theostrepton STREPTOGRAMINS Virginiamycin Dalfopristin/quinupristin Pristinamycin SULPHONAMIDES Phthalylsulfathiazole Sulfachloropyridazine Sulfadiazine Sulfadimethoxine Sulfadimidine Sulfamethazine Sulfamethoxazole Sulfamethoxine Sulfamethoxypyridazine Sulfanilamide Sulfamonomethoxin Sulfanilamide/ Sulphanilamide Sulfaquinoxaline Sulfathiazole Sulfonamides NO CLASSIFICATION Fosfomycin / Phosphomycin Lindomycin Methenamine TETRACYCLINES Anlamycin / Alamycin Aureomycin Chlortetracycline Doxycycline Hydromycin Minocycline Oxytetracycline Terramycin Tetracycline TRIMETHOPRIM Tetroxoprim Trimethoprim Trimoxazole PLEUROMUTILINS Tiamulin
List of Registered Veterinary Products by National Pharmaceutical Regulatory Agency 656 products registered (until July 2017) Macrolide Tilmicosin, Tylosin, Tiamulin (15%) β-lactam Amoxicillin, ceftiofur (9% ) Sulphonamide SDZ, SMZ, SQX (8.2% ) Tetracycline OTC, Doxy, CTC (7.5% ) Fluoroquinolone Enrofloxacin, marbofloxacin (7%) Amphenicol Florfenicol (6.4% ) Aminoglycoside - Gentamycin, neomycin (5%) Anthelmintic Ivermectine (5%) Anticoccidial Salinomycin, nicarbazine (4.9% ) Colistin sulphate (4.3%)
Peratusan (%) penggunaan antibiotik di ladang ayam adalah seperti berikut; Kumpulan Antibiotik Sebatian Bil. Ladang % B-lactam Amoxicillin 106 48.6 Fluoroquinolone Enrofloxacine 98 45 Fluoroquinolone Norfloxacine 41 18.8 Macrolide Tylosin 41 18.8 Anticoccidial Amprolium 41 18.8 Phosphonic a/b Fosfomycin 38 17.4 Aminoglycodie Erythromycin 34 15.6 Macrolide Tilmicosin 27 12.4 piperazine Piperazine 26 11.9 Aminoglycoside Neomycin 15 6.9 Cephalosporin Cephalexin 15 6.9 Polymyxin Colistin 15 6.9 dihydrofolate Reductase Inhibitors Trimethroprim 15 6.9 Sulfonamide Sulfachloropyrazine 15 6.9 Sulfonamide Sulfadiazine 14 6.4
Rational use of antimicrobials with the purpose of optimising both efficacy and safety in animals Comply with the ethical obligation and economic need to keep animals in good health Prevent or reduce as far as possible the emergence and transfer of resistant bacteria within animal populations Maintain the efficacy of antimicrobial agents used in livestock
Prevent or reduce the transfer of resistant bacteria from animals to humans Prevent the contamination of animal-derived food with antimicrobial residues that exceed the established maximum residues level (MRL) Maintain the efficacy of antimicrobial agents used in human medicine and prolong their usefulness Protect consumer health by ensuring the safety of food of animal origin
Communication, consensus, training: between the relevant professionals, acting for the prudent use Need for all countries to start a programme on the responsible and prudent use of antimicrobials
Containment of antibiotic resistance and residues Consumers too have a role to play Responsibilities of regulatory authorities Responsibilities of agriculture producers Antibiotic Use Responsibilities of doctors and veterinarians* Responsibilities of animal feed manufacturers Responsibilities of pharmaceutical industries, distributors *Antibiotic stewardship promotes the use of the right antibiotic, at the right dose, route and duration, for the right bacterial infection at the right time Dryden et al (2009)
Responsible and prudent use of antimicrobial agents in veterinary medicine (1) #Responsibilities of the regulatory authorities Marketing autorisation Submission of data for the granting of the marketing autorisation Market approval registration procedures Quality control of antimicrobial agents Assessment of therapeutic efficacy Assessment of the potential of antimicrobials to select for resistance
# Responsibilities of the regulatory authorities Establishment of acceptable daily intake, maximum residue level and withdrawal periods for antimicrobial compounds Protection of the environment Establishment of a summary of product characteristics for each veterinary antimicrobial product (VAP) Post-marketing antimicrobial surveillance Supply and administration of the antimicrobial agents used in veterinary medicine Control of advertising Training of antimicrobial users Research Responsible and prudent use of antimicrobial agents in veterinary medicine (2)
Responsible and prudent use of antimicrobial agents in veterinary medicine (4) # Responsibilities of wholesale and retail distributors Distribution only on prescription Detailed records Training
Responsible and prudent use of antimicrobial agents in veterinary medicine (5) # Responsibilities of veterinarians Use of antimicrobial agents Choosing an antimicrobial agent Appropriate use of the antimicrobial chosen Recording Labelling Training
Responsible and prudent use of antimicrobial agents in veterinary medicine (6) # Responsibilities of food-animal producers Good farming Practice Use of antimicrobial agents only on prescription Respect the dosages Respect the storage conditions Respect hygienic conditions Respect the recommended withdrawal periods Disposal of surplus antimicrobials under safe conditions for the environment Keeping of adequate records (medicines used; laboratory results) Report to the responsible veterinarian of recurrent disease problems
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