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, antibioticsare, in most cases, compounds produced by a fungusor another microorganism that kill or inhibit thegrowth of bacteria that cause disease in humans oranimals

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

poultry

2. Prophylaxis (prevention)

- Group administration

- in feed and water

- Intermediate duration

‘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)’

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

‘The mass treatment of animal populations

currently experiencing any level of disease before

the onset of blatant illness’

Control of bovine respiratory

disease (BRD) in feedlot cattle

4. Treatment

-targeted invidual (s)

- injection, in feed and water

- Short duration

‘Administration of an antimicrobial to an animal,

or group of animals, which exhibits frank clinical

disease’

Colibacillosis in calves, pigs or

poultry; BRD, swine respiratory

disease

ANTIMICROBIAL USE PATTERNS

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

Antimicrobial classTotal amount (AGP + Tx use) Amount for( Tx use + prevention) Amount for AGP

All animal species(kg)

All animal species(kg)

All animal species(kg)

Aminoglycosides 13475 875 12600Amphenicols 15225 2625 12600ArsenicalsCephalosporins (all generations) 120 120 01-2 gen. cephalosporins3-4 gen cephalosporins

Fluoroquinolones 4615 4615 0GlycopeptidesGlycophospholipidsLincosamides 3120 120 3000Macrolides 218290 26490 191800NitrofuransOrthosomycins 2520 0 2520Other quinolones 4000 0 4000Penicillins 66020 4220 61800Pleuromutilins 14000 0 14000Polypeptides 98435 875 97560QuinoxalinesStreptogramins 630 0 630Sulfonamides (including trimethoprim) 18000 0 18000Tetracyclines 73920 120 73800

Total kg 532370 40060 492310

AMOUNT SOLD FOR / USED IN ANIMALS BY ANTIMICROBIAL CLASS AND TYPE OF USE IN MALAYSIA (2015) (SOURCE : MAHNIA)

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 MinocyclineSulfanilamide/ Sulphanilamide

Bambermycin Doxycycline Nalidixic acid

Benzyl Penicillin Enoxacin, Neomycin Sulfaquinoxaline

Bicozamycin Enramycin, Norfloxacin Sulfathiazole

Cefadroxil Enrofloxacin, Ofloxacin Sulfonamides

Cefalexin/ CephalexinErythromycin Oleandomycin Terramycin

Flavomycin Oxolinic acid Tetracycline

Cefaloridin Flavophospholipol Oxytetracycline Tetroxoprim

Cefalotin/ CephalothinFlorfenicol Penicillin Thiamphenicol

Flumequine Phthalylsulfathiazole Tiamulin

CefamandolFosfomycin/ Phosphomycin

Polymyxin Tilmicosin

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

AMINOGLYCOSIDES &

AMINOCYCLITOLS

Amikacin

Apramycin

Destomycin

Dihydrostreptomycin

Framycetin

Gentamicin

Hygromycin b

Kanamycin

Neomycin

Netilmycin

Paromomycin

Spectinomycin

Streptomycin

Tobramycin

AMPHENICOLS

Chloramphenicol

Florphenicol

Thiamphenicol

CEPHALOSPORINS

Cephalosporins 1st 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 2nd

Gen

Cefuroxime

Cefaclor

Cefamandole

Cefmetazole

Cefonicid

Cefotetan

Cefoxitin

Cefprozil (cefproxil)

Cefuzonam

Cephalosporins 4th

Gen

Cefclidine

Cefepime

Cefluprenam

Cefoselis

Cefozopran

Cefpirome

Cephalosporins 3rd Gen

Cefoperazone

Ceftiofur

Ceftriaxonne

Cefquinome

Cefcapene

Cefdaloxime

Cefdinir

Cefditoren

Cefetamet

Cefixime

Cefmenoxime

Cefodizime

Cefotaxime

Cefpimizole

Cefpodoxime

Cefteram

Ceftibuten

Ceftiolene

Ceftizoxime

Ceftazidime

Cephalosporins 5th Gen

Ceftobiprole

Ceftaroline

Cephalosporins (Not

Classified)

Cefaclomezine

Cefaloram

Cefaparole

Cefcanel

Cefedrolor

Cefempidone

Cefetrizole

Cefivitril

Cefmatilen

Cefmepidium

Cefovecin

Cefoxazole

Cefrotil

Cefsumide

Cefuracetime

Ceftioxide

TABLE 1. ANTIBIOTICS USAGE IN FEED LISTED UNDER ANTIMICROBIAL CLASS IN MALAYSIA (2017)

FLUOROQUINOLONES

Danofloxacin

Difloxacin

Enrofloxacin

Marbofloxacin

Orbifloxacin

Fluoroquinolones 1st

Gen

Piromidic acid

Pipemidic acid

Rosoxacin

Fluoroquinolones 2nd

Gen

Cifloxacin

Ciprofloxacin

Enoxacin

Lomefloxacin

Nadifloxacin

Norfloxacin

Ofloxacin

Pefloxacin

Rufloxacin

Fluoroquinolones 3rd

Gen

Balofloxacin

Gatifloxacin

Grepafloxacin

Levofloxacin

Moxifloxacin

Pazufloxacin

Sparfloxacin

Temafloxacin

Tosufloxacin

Fluoroquinolones 4th

Gen

Besifloxacin

Clinafloxacin

Gemifloxacin

Sitafloxacin

Trovafloxacin

Prulifloxacin

Besifloxacin

LINCOSAMIDES

Clindamycin

Lincomycin

Pirlimycin

ORTHOSOMYCINS

Avilamycins

OTHER QUINOLONES

Flumequine

Nalidixic Acid

Oxolinic Acid

PENICILLINS

Narrow-spectrum β-

Lactamase-sensitive

Penicillins

Penicillin G

(benzylpenicillin)

Penicillin V [

phenoxymethyl-penicillin]

Phenethicillin

Broad-spectrum β-Lactamase-sensitive PenicillinsAmpicillin

Amoxicillin

Hetacillin

Pivampicillin

Talampicillin

Clavulanate-potentiated

amoxicillin

Mecillinam

Broad-spectrum β-Lactamase–sensitive Penicillins with Extended Spectracarboxypenicillins

(carbenicillin)

carboxypenicillins

(ticarcillin)

ureido-penicillins

(azlocillin)

ureido-penicillins (

mezlocillin)

piperazine penicillins

(piperacillin)

Narrow-spectrum β-Lactamase–resistant Penicillinsoxacillin

cloxacillin

dicloxacillin

flucloxacillin

Methicillin

nafcillin

Temocillin

Carbapenems

Imipenem

meropenem

GLYCOPHOSPHOLIPIDS

Bambermycin

Flavomycin

Flavophospholipol

TABLE 2. ANTIBIOTICS USAGE IN FEED LISTED UNDER ANTIMICROBIAL CLASS IN MALAYSIA (2017)

PLEUROMUTILINS

Tiamulin

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

TETRACYCLINES

Anlamycin / Alamycin

Aureomycin

Chlortetracycline

Doxycycline

Hydromycin

Minocycline

Oxytetracycline

Terramycin

Tetracycline

POLYETHERS IONOPHORES

Lasalocid

Monensin

Salinomicin

Narasin

Maduramicin

Theostrepton

Semduramicin

NO CLASSIFICATION

Fosfomycin /

Phosphomycin

Lindomycin

Methenamine

MACROLIDES

Aivlosin

Amphotericin B

Clarithromycin

Erythromycin

Gamithromycin

Josamycin

Kitamycin

Kitasamycin

Leucomycin

Oleandomycin

Spiramycin

Tildipirosin

Tilmicosin

Tulathromycin

Tylosin

Tylvalosin

Isovaleryl Tylosin

ANTIPROTOZOALS

Robenidine

TRIMETHOPRIM

Tetroxoprim

Trimethoprim

Trimoxazole

TABLE 3. ANTIBIOTICS USAGE IN FEED LISTED UNDER ANTIMICROBIAL CLASS IN MALAYSIA (2017)

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

http://www.oie.int/eng/normes/mcode/en_chapitre_1.6.9.htm

• 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 programmeon “the responsible and prudent use of antimicrobials”…

Containment of antibiotic resistance and residues

Antibiotic Use

Responsibilities of regulatory authorities

Responsibilities of doctors and

veterinarians*

Responsibilities of pharmaceutical

industries, distributors

Responsibilities of agriculture producers

Responsibilities of animal feed

manufacturers

*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)

Consumers

too have a role

to play

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 withdrawalperiods for antimicrobial compounds

| Protection of the environment

| Establishment of a summary of product characteristics for each veterinaryantimicrobial product (VAP)

| Post-marketing antimicrobial surveillance

| Supply and administration of the antimicrobial agents used in veterinarymedicine

| Control of advertising

| Training of antimicrobial users

| Research

Responsible and prudent use of antimicrobial agents in veterinary medicine (2)

# Responsibilities of wholesale and retail distributors

| Distribution only on prescription

| Detailed records

| Training

Responsible and prudent use of antimicrobial agents in veterinary medicine (4)

# 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 (5)

# 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

Responsible and prudent use of antimicrobial agents in veterinary medicine (6)

Terima kasih

Thank you