GB2033224A

GB2033224A - Trimethoprim/ sulphachloropyrazine compositions

Info

Publication number: GB2033224A
Application number: GB7934883A
Authority: GB
Original assignee: Marxer SpA
Current assignee: Marxer SpA
Priority date: 1978-10-09
Filing date: 1979-10-08
Publication date: 1980-05-21
Also published as: FR2438480A1; NL7907483A; IT1099795B; IT7828549A0; DE2940934A1; AU5161579A; GR73098B

Abstract

Bacterial infections of poultry, turkeys, rabbits, sucking calves and swine, and coccidiosis of poultry, turkeys and rabbits are treated with a composition comprising sulphachloropyrazine and 5-[(3,4,5- trimethoxyphenyl)-1-methyl]-2,4- pyrimidindiamine (trimethoprim). The compositions are preferably in the form of animal feed or drink compositions.

Description

SPECIFICATION Therapeutical composition for the treatment of infections and diseases of breeding animals.

The present invention relates to a composition useful for the treatment of some infections and diseases of breeding animals, particularly poultry, turkeys, rabbits, sucking calves and swine. More specifically the present invention relates to a therapeutical composition for the treatment of the bacterial infections of the above mentioned breeding animals, as well as of the coccidiosis of poultry, turkeys and rabbits. The importance of the problem faced by the present invention is well known to those skilled in the art and it is not necessary a more detailed illustration thereof.It is to be mentioned the well known fact of the frequency and quickness with which the bacteria responsible of the infections acquire a "resistance" property towards sulphamidic and antibiotic drugs used for the therapy (the same phaenomena occurring in the case of coccidia towards the sulphamides used for the therapy of the coccidiosis).

The problem of the "resistance" can be overcome by using new active principles (thus depending on the basic scientific research work which is not always fruitful and, mainly, does difficulty keep up with the afore mentioned features of frequency and quickness), or by having recourse to novel combinations of known active substances, developing synergies previously unknown.

The present invention fails within said second research approach and consists of a therapeutical composition for the treatment of bacterial infections and coccidiosis of poultry, turkeys, rabbits, sucking calves and swine, characterized by that it contains in combination, as the active ingredients, sulphachloropyrazine and 5-[(3,4,5-trimethoxyphenyl) methyl ]- 2,4-pyrimidindiamine.

More specifically the therapeutical composition of the present invention provides for the combination of the two active ingredients in a ratio between sulphachloropyrazine and 5-[(3,4,5 trimethoxyphenyl)-methyl]-2,4-pyrimidindiamine (also known under the non chemical name "Trimetoprim") of between 4:1 and 8:1 by weight.

The sulphachloropyrazine is a sulphamidic substance known for its anti-coccidic activity or for the inhibition of the growth,of coccidia, whereby it has been always used against aviary coccidiosis (pouitry and turkeys), whereas it has been never used for the therapy of coccidiosis in the rabbits nor as an anti-bacterial compound for the therapy of bacterial infections of poultry, turkeys, rabbits, sucking calves and swine. It is to be remembered that in the known uses of the sulph-chloropyrazine against the coccidiosis, such a substance is active at dosages of 0,6 g/kg of foodstuff as well as of 0,3 g/lt of drinking water, with a duration of the therapeutical treatment of about 6 days. As regards the antibacterial activity, it can be appreciated only for very high doses of about 4g/kg of foodstuff and 2g/lt of drinking water.

It is thus confirmed what has been previously stated, namely that sulphachloropyrazine to date has exclusively found application in the therapy of the aviary coccidiosis.

The Trimetoprim is the sulphamidic substance now used in drugs for human use (Bactrim, Eusaprim) and for veterinary use (Animar, Borgal, Duoprim, Tinkanium) in combination with other sulphamidic compounds having anti-bacterial action onlv.

The Trimetoprim, by itself, shows a rather modest antibacterial action, but has the known property of enhancing the anti-bacterial action of other sulphamidic compounds having such an activity. Lastly, this active compound has never been used to date in preparations for the treatment of aviary and rabbits coccidiosis, nor such an use was foreseeable on the basis of the available information.

The therapeutical composition of the present invention, in which the sulphachloropyrazine and the Trimetoprim are combined, has consequently surprising properties and results under several points of view, since: it permits the sulphachloropyrazine to be used as an anti-bacterial agent at doses which can be used as an alternative with respect to sulphamides and antibiotics of common use; it determines a higher therapeutical efficiency of the sulphachloropyrazine towards the aviary coccidiosis (poultry and turkeys) due to the synergic action with Trimetoprim, the combination being thus a novel anti-coccidic agent; it permits the posology to be reduced both as regards the dosage and as regards the duration of treatment at which the sulphachloropyrazine alone shows its therapeutical activity against aviary.

coccidiosis (poultry and turkeys) the problem of residues in the meat and in the eggs being completely negligible; it permits the therapeutical use, to date never known, of the sulphachloropyrazine against the rabbit coccidiosis; it permits a novel therapeutical use of Trimetoprim as a potentiating agent of anti-coccidic sulphamides, besides the same effect with respect to the anti-bacteria coccidia.

As a confirmation of the preceding considerations, it has been in fact found that by means of the composition of the present invention the anti-bacterial activity occurs at a concentration of the sulphachloropyrazine of about 0.1 g/lt of water, whereas, as already mentioned, the anti-bacterial activity of the sulphachloropyrazine alone is meaningful only for dosages twenty times higher.

In turn, as regards the therapeutical activity against aviary coccidiosis, it becomes remarkable for concentrations of sulphachlbrnpyrazine of 1 g/kg of foodstuff and of 0.05 g/lt of drinking water, which means, if a comparison is made with the data above referred to and relating to the sulphachloropyrazine only, that the combination with the Trimetoprim permits, the therapeutical effect being the same, the dosage of the sulphachloropyrazine to be reduced by more than 83%.

Lastly, also the duration of the therapeutical treatment is reduced since such a duration with the composition of the present invention is reduced to 2-3 days only linstead of 6).

To sum up, the therapeutical composition of the present invention has the following advantages: Is a novel drug for the therapy of bacterial infections and coccidiosis in the animals of zootechnical interest. The two active compounds (sulphachloropyrazine and Trimetoprim), as a matter of fact, are effective in two different and successive steps of the metabolic cycle of bacteria and coccidia. The sulphachloropyrazine prevents the pteroylglutamic acid, and thus the folic acid, from being formed, whereas the Trimetoprim inhibits the synthesis of the purines, and thus of DNA, by inhibiting the dihydrofolic reductase enzime, (by which the conversion of dihydrofolic acid to tetrahydrolic acid is catalytically promoted). It is to be pointed out that no antibiotic has a mechanism of action like that of the above therapeutical composition.On the other side the sulphamides, when used alone, show a therapeutical effect less efficient and less complete than that of the present therapeutical composition, since their action does only refer to the first of the two above described steps, (i.e. inhibition of the formation of the pteroylglutamic acid).

Owing to its different and novel mechanism of action, the composition of the present invention is active against bacteria and coccidia, which became "resistant" towards sulphamides and antibiotics of common use, whereby reliable therapeutic results can be ensured, differently from the prior art sulphamides and antibiotics. The possibility of the growing of "resistant" species is reduced, because the present composition is active in two different and successive steps of the metabolic cycle of bacteria and coccidia.

It is endowed with bactericidal activity, differently from the sulphamides which, when used alone, have a mainly bacteriostatic activity.

With respect to the antibiotics and sulphamides of common use has a definitely lower "suspension time", both because Trimetoprim as a matter of fact does not give place to residues in parenchyma, muscles and eggs, and because the sulphachloropyrazine is present at very reduced doses.

For the clinical experiments the sulphachloropyrazine has been used in combination with the Trimetoprim in preparations having the following composition: Prep. No 1) Sulphachloropyrazine Na 50 g Trimetoprim HCI 12.5 g

} ratio 4:1 Lactose F.U. as needed to get 1,000 g.

Preparation No. 2 sulphachloropyrazine Na 50 g Trimetoprim HCI 10 g

} ratio 5:1 Lactose Fb as needed to get 1,000 g.

Prep. No. 3) Sulphachloropyrazine Na 50 g Trimetoprim HCI 6.25 g

} ratio 8:1 Lactose F.U. as needed to get 1,000 g.

The three preparations have been used either in admixture with the foodstuff, or, due to their complete solubility, as a solution in drinking water and in the (restored) substitutes of the milk for the calves or in the foodstuff for swine. The experiments, the results of which are reported in the tables 14 - have been carried out as follows: Preparation No. 1 Poultry: 10,000 Leghorn cockerels, affected with respiratory chronical disease (MCR) 545 egg layers affected with aviary cholera; 350 breeders affected with coryza; 850 broilers affected with colisepticaemia; 200 chickens experimentally infested with Eimeria tenella (a highly pathogenic coccidium species); 2,500 breeders affected with coccidiosis induced by Eimeria acervulina.

Turkeys: 400 meat turkeys affected with colibacilosis; 250 breeders affected with colibacillosis; 300 young turkeys experimentally infected with Eimeria adenoides (highly' pathogenic coccidium species).

Rabbits: 200 meat rabbits affected with intestinal coccidiosis; 1 50 breeders affected with colibacillosis.

Preparation No. 2 Poultry: 6,000 broilers affected with respiratory chronical disease (MCR); 1,870 egg layers affected with aviary cholera; 1,215 breeders affected with coryza; 4,350 broilers affected with colisepticaemia.

6,000 pullets affected with staphylococcosis; 3,200 pullets affected with intestinal salmonellosis; 1,800 broilers affected with coccidiosis induced by Eimeria tenella: 9,000 broilers affected with coccidiosis induced by Eimeria necatrix; 4,500 pullets affected with coccidiosis induced by Eimeria acervulina.

Turkeys: 1,12z0 meat turkeys affected with respiratory symptomatology (MCR); 560 breeders affected with colibacillosis; 3,000 meat turkeys affected with Leucocytozoonsp.; 5,300 meat turkeys affected with aviary cholera; 1,800 breeders affected with staphylococcosis; 4,100 meat turkeys affected with infection induced by Erysipelothrix rhusiopathiae; 9,600 meat turkeys affected with coccidiosis induced by Eimeria meleagridis; 11,250 meat turkeys affected with coccidiosis induced by Eimeria meleagrimitis.

Rabbits: 425 breeders affected with colibacillosis; 1,200 meat rabbits affected with respiratory simptomatology (pasteurellosis) 1 50 breeders affected with staphylococcosis 950 meat rabbits affected with intestinal coccidiosis.

Preparation No. 3 Poultry: 2,390 egg layers affected with aviary cholera; 2,150 breeders affected with coryza; 6,000 broilers affected with colisepticaemia; 7,500 broilers affected with respiratory symptomatology (CRD); 30,000 quails affected with colibacillosis and salmonellosis; 850 breeders affected with staphylococcosis; 1,800 pullets affected with intestinal salmonellosis; 8,080 broilers affected with coccidiosis induced by E. tenella; 11,600 broilers affected with coccidiosis induced by Eimeria acervulina; 3,850 breeders affected with coccidiosis induced by E. necatrix.

Turkeys: 1,920 meat turkeys affected with colibacillosis; 1,250 breeders affected with colibacillosis; 1,800 meat turkeys affected with respiratory symptomatology (MCR) 4,150 meat turkeys affected with aviary cholera; 1 ,1 00 breeders affected with staphylococcosis; 3,040 meat turkeys affected with infection induced by Erysipelothrix rhusiopathiae; 2,100 meat turkeys affected with coccidiosis induced by E. adenoides; 1,300 meat turkeys affected with coccidiosis induced by E. meiea-grimitis.

4,100 meat turkeys affected with coccidiosis induced by E. meleagridis.

Rabbits: 800 meat rabbits affected with colibacillosis; 450 breeders affected with staphylococcosis; 1,050 meat rabbits affected with respiratory symptomatology (pasteurellosis); 300 meat rabbits affected with pulmonary diplococcosis; 1,400 meat rabbits affected with coryza; 1,750 meat rabbits affected with intestinal coccidiosis.

Sucking Calves: 582 animals affected with enzootic bronchopneumonia; 429 animals affected with shipping fever; 318 animals affected with catarral gastroenteritis; 873 animals affected with infectious polyarthritis; 301 animals affected with infectious onphalo phlebitis; Swine: 1,062 animals affected with respiratory syndrome (enzootic pneumonia); 796 animals affected with catarral gastroenteritis (neonatal collibacillosis): 1,500 animals affected with catarral gastroenteritis (weaning colibacillosis); 560 animals affected with infectious polyarthritis.

It is to be pointed out that: 1) All the tests, apart from the experimental infections (in poultry and turkeys) with Eimeria sp., were effected in field.

2) The preparation No. 1 was used to assess, in an absolute manner, the efficacy of the composition in animals, affected with bacterial infections or coccidiosis, which previously had not been subjected to any therapeutical treatment.

3) The preparations Nos. 2 and 3 were used for several groups of sick animals, which previously had been subjected, without positive effect, to therapeutical treatments with antibiotics or sulphamides.

4) In the sucking calves and in swine only the preparation No. 3 was used, since it had already given highly positive results in the other animals species.

TABLE 1 POUL TRY

1 2 3 4 5 6 7 8 9 10 % % % % % % % % % % No. of re- No. of re- No. of re- No. of re- No. of re- No. or re- No. of re- No. of re- No. of re- No. of re cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery prep. No. 1 10000 86 350 98 545 97 850 95 200 100 2500 96 - - - - - - - prep. No. 2 6000 84 1215 96 1870 98 4350 94 - - 4500 95 6000 91 3200 86 1800 92 9000 94 previous A A E E M A E M M treatments B B F F N F H N N C E G G F G I F F I H L H H prep. No. 3 7500 84 2150 95 2390 95 6000 94 - - 11600 93 850 93 1800 85 8080 91 3860 95 + 30000 88 previous A A E E M A E M M treaiments D E F F N E H N N F H H F H I F F L I H L H H TABLE 1 - LEGEND Posology of the therapeutical treatments carried out before the use of the preparations Nos. 2 and 3 (doses expressed as grams of active compound) A) Spiramycine: 20 g/1 00 Its of drinking water for 4 days.

B) Eritromycin: 25 g/100its of drinking water for 4 days.

C) Spectinomycin: 50 g/100 its of drinking water for 4 days.

D) Tilosine: 50 g/1 00 Its of drinking water for 3 days.

E) Tetracyclines: 80 9/100 kg of foodstuff for 5 days.

(CTC-OTC-TC) F) Sulphametazine: 300 g/l 00 kg of foodstuff for 4 days.

G) Sulphachloropyridazine: 80 9/100 kg of foodstuff for 4 days.

H) Sulphadimethoxine + diaveridine (10 + lOg): 20 g/100 Its of drinking water for 4 days.

I) Furaltadone tartrate: 1 5 g/100its of drinking water for 4 days.

L) Furazolidone: 20 g/1 O0 Its of drinking water for 5 days.

M) Sulphaquinoxaline: 50 9/100 Its of drinking water for 3 days.

N) Amprolium + Etopabate: 25.5 g/100 Its of drinking water for 3 days.

(25 + 1.6g) Posology of the preparations Nos. 1,2,3: 200 g/100 kg of foodstuff or 1 00 g"'1 0O Its of drinking water (these dosages are expressed as grams of preparation namely active compounds and lactose).

Patologies undergoing the treatment 1) Respiratory chronical disease (MCR): treatment in drinking water for 3 days.

2) Infectious coryza: treatment through the foodstuff for 3 days.

3) Aviary cholera: treatment through the foodstuff for 3 days.

4) Colisepticaemia: treatment in drinking water for 3 days.

5) Experimental infection induced by E. tenella: treatment in drinking water for 3 days.

6) Coccidiosis induced by E. acervulina: treatment in drinking water for 3 days.

7) Staphylococcosis: treatment through the foodstuff for 4 days.

8) Intestinal salmonellosis: treatment in drinking water for 4 days.

9) Coccidiosis induced by E. tenella: treatment in drinking water for 3 days.

10) Coccidiosis induced by E. necatrix: treatment in drinking water for 3 days.

TABLE 2 TURKEYS

11 12 13 14 15 16 17 18 19 20 % % % % % % % % % % No. of re- No. of re- No. of re- No. of re- No. of re- No. or re- No. of re- No. of re- No. of re- No. of re cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery Prep. No. 1 400 96 + 300 94 - - - - - - - - - - - - - - - 250 98 Prep. No. 2 560 95 - - 1040 88 3000 79 5300 94 1800 91 4100 90 9600 89 11250 95 - previous E - A H E F E M M treaiments I B M F G H N N L F G E I F F F H F Prep.No. 3 1820 95 - - 1800 95 - - 4150 94 1100 93 3040 89 4100 92 1300 94 2100 94 + 1250 97 previous E - A - E H E M M M treatments H B G G H N N N I C H F G F F F L D H H H G TABLE 2 - LEGEND Posology of the therapeutical treatments carried out before the use of the preparations Nos. 2 and 3 (doses expressed as grams of active compound) A) Spiramycine: 20 9/100 Its of drinking water for 4 days.

B) Eritromycin: 25 g/100 Its of drinking water for 4 days.

C) Spectinomycin: 50 gIl 0O Its of drinking water for 4 days.

D) Tilosine: 50 g/l 00 Its of drinking water for 3 days.

E) Tetracyclines: 80 9/100 kg of foodstuff for 5 days.

(CTC-OTC-TC) F) Sulphametazine: 300 g/l 00 kg of foodstuff for 4 days.

G) Sulphachloropyridazine: 80 g/l 00 kg of foodstuff for4 days.

H) Sulphadimethoxine + diaveridine (10 + 10 g): 20 9/100 Its of drinking water for 4 days.

I) Furaltadone tartrate: 1 5 g/l 00 Its of drinking water for 4 days.

L) Furazolidone: 20 g/l00 Its of drinking water for 5 days.

M) Sulphaquinoxaline: 50 9/100 Its of drinking water for 3 days.

N) Amprolium + Etopabate: 25.5 g/l 00 Its of drinking water for 3 days.

(25 + 1.6 g) Posology of the preparations Nos. 1,2,3: 200 g/l 00 kg of foodstuff or 100 g/l 00 Its of drinking water (these dosages are expressed as grams of preparation, namely active compounds and lactose).

Treated pathologies 11) Colibacillosis: treatment in drinking water for 3 days.

12) Experimental infection induced by E. adenoides: treatment in drinking water for 3 days.

13) Respiratory chronical disease (MCR): treatment in drinking water for 3 days.

14) Infection induced by Leucocytozoon sp.: treatment in drinking water for 4 days.

15) Aviary cholera: treatment in the foodstuff for 3 days.

16) Staphylococcosis: treatment in the foodstuff for 4 days.

17) Infection induced by Erysipelothrixrhusiopathiae: treatment in drinking water for 3 days.

18) Coccidiosis induced by E. meleagridis: treatment in drinking water for 3 days.

19) Coccidiosis induced by E. meleagrimitis: treatment in drinking water for 3 days.

20) Coccidiosis induced by E. adenoides: treatment in drinking water for 3 days.

TABLE 3 RABBITS

21 22 23 24 25 26 % % % % % % % % % % No. of re- No. of re- No. of re- No. of re- No. of re- No. or re- No. of re- No. of re- No. of re- No. of re cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery Prep. No. 1 200 93 150 98 - - - - - - - Prep. No. 2 950 91 425 94 1200 90 150 89 - - - previous O E E E - treatments P P P Q O Q Q P E+Q Prep. NO. 3 1750 90 800 94 1050 91 450 91 300 83 1400 94 previque O E E E E E treatments P P P Q Q P Q Q Q P E+Q E+Q E+Q TABLE 3-LEGEND Posology of the therapeutical treatments carried out before the use of the preparation Nos. 2 or 3 (dosages expressed as grams of active compound) E) Tetracyclines: 80 g/l 00 kg of foodstuff for 5 days.

(CTC-0TC-TC) O) Sulphaquinoxaline: 1 50 g/l 00 kg of foodstuff for 4 days.

P) Sulphadimethoxine: 150g/100kg of foodstuff for 4 days.

Q) Sulphametazine: 200 g/100 kg of foodstuff for 4 days.

Posology of preparations Nos. 1 2,3: 200 g/l 00 kg of foodstuff or 100 g/100 its of drinking water (dosages expressed as grams of preparation, namely active compounds + lactose).

Treated pathologies 21) Intestinal coccidiosis: treatment in drinking water for 3 days.

22) Colibacillosis: treatment in drinking water for 3 days.

23) Respiratory symptomatology (pasteurellosis): treatment in drinking water for 3 days.

24) Staphylococcosis: treatment inthe foodstuff for 4 days.

25) Pulmonary diplococcosis: treatment in drinking water for 3 days.

26) Coryza: treatment in drinking water for 3 days.

TABLE 4 SUCKING CALVES SWINE

27 28 29 30 31 32 33 34 35 % % % % % % % % % No. of re- No. of re- No. of re- No. of re- No. of re- No. or re- No. of re- No. of re- No. of re- No. of re cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery cases covery Prep.NO. 3 582 90 429 85 318 88 873 91 301 76 1602 94 796 79 1500 88 560 92 previous R R V K J X X X X treatments S S R R U Y a a b T U Z V K W b b d U V+S K J R X+Y c c TABLE 4-LEGEND Posology of the therapeutical treatments carried out before the use of the preparation No. 3 {dosages expressed as grams of active compound) CALVES R) Tetracyclines: 5 gr/100 kg. of living weight, (CTC-OTC-TC) in the foodstuff, for 4 days.

S) Spiramycin: 8 gr/100 kg of living weight, in the foodstuff, for 4 days.

T) Sulphamethazine: 1 50 g/l 00 kg of living weight, in the foodstuff, for 4 days.

U) Chlorotetracycline + Sulphamethazine (4 + 129): 169/1 00 kg of living weight, in the foodstuff, for 4 days.

V) Furaltadone tartrate: 2 Q/100 kg of living weight, in the foodstuff, for 4 days.

Z) Formylsulphathiazole: 12 g/l 00 kg of living weight, in the foodstuff, for 4 days.

K) Sulphachloropyridazine: 8 9/100 kg of living weight, in the foodstuff, for 4 days, J) Sulphadimethoxine + diaveridine (1.5 + 1 .5g): 3 g/l 00 kg of living weight, in the foodstuff, for 4 days.

SWINE X) Tetracyclines: 4 9/100 kg of living weight, in the foodstuff, for 4 days.

(CTCTC-TC) Y) Spiramicin: 1.5 g/l 00 kg of living weight, in the foodstuff, for 4 days.

W) Tilosine: 0.4 g/l 00 kg of living weight, in the foodstuff, for 5 days.

a) Formylsulphathiazole: 18 Q/100 kg of living weight, in the foodstuff, for 4 days.

b) Sulphadimethoxine: 5 9/100 kg of living weight, in the foodstuff, for 4 days.

c) Furaltadone tartrate: 2.5 g/l 00 kg of living weight, in the foodstuff, for 4 days.

d) Sulphamethazine: 20 9/100 kg of living weight, in the foodstuff, for 4 days.

Posology of the preparation No. 3.

Calves: 20 9/100 kg of living weight (2 administrations/day).

Swine: 30 Q/100 kg of living weight (2 administrations/day).

(dosages expressed as grams of preparation, namely active compounds + lactose).

Treated pathologies.

Calves 27) Enzootic pneumonia: treatment in the foodstuff for 4 days.

28) Shipping fever: treatment in the foodstuff for 4 days.

29) Neonatal colibacillosis: treatment in the foodstuff for 3 days.

30) Infectious polyarthritis: treatment in the foodstufffor4 days.

31) Infectious onphalophlebitis: treatment in the foodstuff for 3 days.

Treated Pathologies Swine 32) Respiratory syndrome: treatment in the foodstuff for 3 days.

(enzootic pneumonia) 33) Neonatal colibacillosis: treatment in the foodstuff for 3 days.

34) Weaning colibacillosis: treatment in the foodstuff for 3 days.

35) Infectious polyarthritis: treatment in the foodstuff for 4 days.

Both sulphachloropyrazine and Trimetoprim are well known compounds, whereby, for sake of brevity, the processes for their preparation are not described, and reference is made to the technical literature for whatever information in this connection.

Claims

1. An anti-bacterial composition comprising, as an active constituent, a combination of sulphachloropyrazine and trirnethoprim.

2. A composition as claimed in claim 1 , wherein the ratio of sulphachloropyrazine to trimethoprim is from 4:1 to 8:1 by weight.

3. A composition as claimed in either claim 1 or claim 2, wherein the amount of sulphachloropyrazine is present in an amount of about 0.1 g per kg of total composition.

4. A composition as claimed in any one of claims 1 to 3, wherein the active constituent is added to an animal feed or drink composition.

5. A composition as claimed in any one of claims 1 to 4 for use in the treatment of bacterial infections of poultry, turkeys, rabbits, suckling calves and swine, and of coccidiosis of poultry, turkeys and rabbits.

6. A composition as claimed in claim 1 and substantially as hereinbefore described.