sou · GLB3132d1 · 1998-01-01 00:00:00 — The feeding strategies employed were developed through close collaboration between the feed industry and the farmers. As mentioned, the coccidiostats of the ionophore type that are now used do have antibacterial effects and act prophylactically against necrotic enteritis. However, the sanitary situation of broiler chicken rearing in today would not have been reached without the above mentioned enforcements. After the ban, coccidiostats were prescribed as medicated feed. Close monitoring of the efficiency of coccidiostats was introduced in in 1986. Since 1991, the efficiency of the drugs is studied by lesion scoring (according to methods described by and , 1970) in approximately of the Swedish broiler flocks, representative of all individual feed mills. The results are used for surveillance of the coccidiosis situation and to adapt the coccidiostatic regimen accordingly. In addition, all broiler flocks are under direct veterinary supervision as part of the salmonella control programme. have never been authorised for use in laying hens in . Consequently, the ban in 1986 had no impact on the egg production. Following the ban, coccidiostats were prescribed as medicated feed to replacement birds. This practice is now being gradually replaced by the use of vaccines. The situation for producing units was similar to that for production of broiler chickens. Before 1986, were used for prevention of necrotic enteritis. The ban did not result in noticeable clinical problems or reduced growth rate. Before 1986, practically all piglets were given (olaquindox or carbadox), from weaning until delivery to the finishing units at the age of 10- 12 weeks. Slaughter pigs were, to a lesser extent, given (avoparcin or virginiamycin) until slaughter. Production averages from 220 piglet producing herds from the years 1985 and 1986 have been assessed statistically (and Lundeheim, 1994). For piglet production, problems emerged as a consequence of the removal of olaquindox which was used for weaning piglets. However, the pre-weaning piglet mortality, and the number of piglets produced per sow and year, did not show significant differences between the two years. In contrast, post- weaning mortality was significantly higher (p<0.001), about 1.5 percentage units, during 1986 than in 1985. The time to reach increased by 5-6 days. Total efforts to prevent post-weaning diarrhoea, including advisory and preventive measures and treatments, increased four-fold. Data from units which were used for the above evaluation has now also been evaluated for the 10-year period 1986-1995. A comparison of the average values for 1994- 1995 and 1986-1987 reveals post-weaning mortality to have decreased with 0.9 percentage units and the age at to have been reduced by 1-2 days (Wierup, 1996). In connection with the ban of it became obvious that clear guidelines for veterinarians on how to prescribe antibiotics as medicated feed were lacking. Such guidelines were adopted by the in 1990 (SVS). The guidelines emphasise that the prescription of feed antibiotics should always be based on a diagnosis together with a thorough evaluation of contributory factors and accompanied by recommendations on hygienic and other prophylactic measures. In a study from 1994, and Lundeheim analysed the results from 55 piglet producing units in the western part of . They concluded that the medicated feed prescribed to weaning pigs was clinically motivated and in accordance with the guidelines formulated by the SVS. The need for medicated feed differed markedly between herds and this could be ascribed to weaning and management systems. The production results were highly correlated to the rearing systems and to the level of hygiene. In herds rearing post weaning pigs on deep bedding the use of medicated feeds was three to four times lower than in herds with pigs in traditional post weaning pens. The study also underlines the problem with preventing weaning diarrhoea in units with limited facilities to arrange satisfactory sectioning and hygiene. Efforts have also been undertaken to make adjustments in the composition of pig feed. The most prominent changes have been a lowering of the protein content, use of water soluble fibres and supplementation with amino acids (, 1995). An antisecretory factor, preventing liquid penetration to the gut induced by enterotoxin, has also been explored as a preventive measure (, 1993). A notable effect on weaning diarrhoea through addition of high levels of zinc oxide has been reported (, 1989; , 1995). Zinc oxide has a preventive effect on weaning diarrhoea equal to the effect which is reached when using olaquindox (, 1994b). Since 1992, zinc oxide is approved for incorporation into piglet feed, at 2000 ppm of zinc. Not all piglet feed contains high levels of zinc, as many producers do not experience problems with weaning diarrhoea. The intention was that the use of zinc oxide would only be temporary, until other measures to prevent weaning diarrhoea had been developed. Presently, the long term impact of the use of zinc oxide is under debate, and is currently considering a phase-out and subsequent ban on the use of zinc oxide in high doses. After the ban of numerous measures have been, and are continuously, undertaken to optimise rearing and production systems and to employ available techniques (e.g. sectioning of , age segregation, planned production). The ban also stimulated a development towards new rearing systems. The weaning of piglets on deep in large groups is one example and the so called birth-to-slaughter system which is based on production in the same pen from birth to slaughter is another. The adjustment of old and pens to the new production system is expensive and until such adjustments can be done antibiotics are used to combat weaning diarrhoea in some units. The experiences from the clinical problems which emerged after the ban indicate that single environmental or rearing measures are seldom enough to correct the situation. A combination of efforts aiming towards a health- orientated production system is often necessary. Many problems have been solved while others await solution. The ban of did not create obvious clinical problems for growing or finishing pigs. The production results from this sector are comparable to those from, for example, the Danish production (source: ). 2.6Sales of antibacterials for veterinary use in Data for 1980-1993 have been compiled from earlier publications (Wierup ET AL , 1987; Björnerot ET AL , 1996). For the years 1994-1996, data have been calculated from the same sources as these authors have used (see table 2.V). All data on pharmaceutical specialities are based on the sales statistics in the (Pharmacies). This system contains registers of all sales from the wholesalers to the local pharmacies (all belonging to Apoteksbolaget), and to the feed companies. As all pharmaceutical specialities are distributed from these wholesalers to local pharmacies or to authorised feed companies, these figures represent the total consumption in . The local pharmacies normally have short storage periods for these products, so it can be assumed that the products sold were also consumed during the respective periods. With regard to antibacterials used as feed additives before 1986, data has been gathered from . Additionally, for 1980-1993 data on sales of unlicenced pharmaceutical specialities, sold with special permission from the were gathered from the respective pharmaceutical companies. The antibacterials included are pharmaceutical specialities approved for general or local use in veterinary medicine (ATCvet1 code QJ01, QJ51, QA07A, QG01A, QP51AA and QP51AG). For 1980-1993, preparations for dermatologic use (ATCvet code QD06, QD07C, QS02C) are also included. For 1980-1984, feed additives not approved as pharmaceutical specialities and thus not delivered through pharmacies were also included. Thus, the statistics show the total amount of antibacterials sold by pharmacies or delivered by feed mills during the specified time period. It was assumed that the whole amount sold was used for animals. The figures include antibacterials for all animal species (food animals, fish, pets and horses). All data are expressed as kilogram of substance. In formerly published data, the weight of the procaine part of procaine penicillin was included in the presentations. As the procaine part of the molecule is not in an antibiotic sense, procaine penicillin has been calculated to benzyl penicillin as 0.6 times the weight of procaine penicillin. Further, some corrections have been made of erroneous macrolide figures. The total usage of antibacterials is presented in table 2.Va. For clarity, table 2.Vb lists examples of pharmaceutical specialities included in the different groups in table 2.Va. Since 1986, the total usage has decreased from a mean on 45 /year during 1980-1984 to 20 in 1996 (a decrease by ). The total sales of formulations intended for treatment of groups of animals, i.e. through feed or water, was about 6 in 1996 (sum of figures in table 2.VI). This means that more than two thirds of the total consumption in 1996 was in the 1 ATC = classification system form of formulations for treatment of individual animals (e.g. parenteral drugs, intramammaries or tablets). As the different substances in question are not equal in their biological activity per weight unit, total figures might be misleading (i.e. if a substance requiring high dosages for full efficacy is replaced by a more substance, a false impression of a reduction could be given). Therefore, each substance group should be assessed separately for trends. Of the pharmaceutical specialities that were authorised at the time of the ban, the sales of G- and V-penicillins, macrolides and trimethoprim- sulphonamides have increased over time. Among the penicillins, only formulations suitable for treatment of single animals (parenteral drugs, tablets) are presently approved. The group consists mainly of formulations for injection and are therefore assumed to be used largely for the treatment of mastitis in dairy cattle (and Greko, 1997). Similarly, the trimethoprim-sulphonamides are only available for treatment of individual animals. About 15 to 20 years ago, the main indication for trimethoprim-sulphonamides in pigs, namely neonatal piglet diarrhoea, was very common. However, due to improved management and housing conditions in combination with efficient vaccines, neonatal piglet diarrhoea is no longer a major clinical problem. The observed increase in consumption is therefore likely to be derived from an increased usage of trimethoprim- sulphonamides in dairy cows and lately, following the introduction of formulations for oral use, in horses. Although the amount of macrolides sold as formulations for injection increased in the beginning of the 90s (and Greko, 1997), the major part of this increase derives from macrolides for oral use (mixed in feed or water). This increase, and that of the pleuromutilins, is believed to reflect an increase in the incidence of swine dysentery (the major indication for those drugs). The increase during 1995 and 1996 is likely to be explained by the fact that the nitroimidazoles, the third category of drugs (formerly) available for this indication, were withdrawn from the market in 1995. The usage of tetracyclines and aminoglycosides has decreased. The changes in the latter group is partly explained by a decrease in usage of the combination of penicillin and dihydrostreptomycin. The usage of tetracyclines will be further commented on below. The consumption of substances formerly approved as feed additives and subsequent to the ban approved as therapeuticals (quinoxalines and streptogramins) has decreased substantially in spite of higher doses being given for therapy than for growth promotion. Total animal usage of antibacterials in animals during 1980-1996 expressed as kg substance (Data for 1980-1993 from Wierup ET AL , 1987; Björnerot ET AL , 1996 and for 1994-1996 Greko, unpublished) 4ABELL 6A 4OTAL F¶RBRUKNING AV ANTIBIOTIKA F¶R ANV¤NDNING TILL DJUR UTTRYCKT SOM KG AKTIV SUBSTANS $ATA FR¥N FR¥N 7IERUP ET AL "J¶RNEROT ET AL OCH FR¥N 'R EKO OPUBLICERAT 9EAR(kg substance) G and V penicillins1 1Procaine penicillin has been calculated to and expressed as bensylpenicinllin as 0.6 times total weight of procaine penicillin 2For 1980-1984 used as feed additives, 1986-1996 on veterinary prescription only at therapeutic dosages 3Including avoparcin, bacitracin, nitrovin, oleandomycin and spiramycin 4For 1980-1995 mainly nitroimidazoles (withdrawn in 1995) Explanations of groups in main table (table 2.Va) 4ABELL 6B &¶RKLARINGAR TILL DE GRUPPER SOM ING¥R I TABELL 6A !CTIVE SUBSTANCE %XAMPLES OF SUBSTANCES INCLUDED G and V penicillins procaine penicillin, benzyl penicillin, phenoxymethyl dihydrostreptomycin, gentamicin, neomycin sulphadiazine, sulphadoxine, formolsulphatiazole avoparcin, bacitracin, nitrovin, oleandomycin and spiramycin as feed additive for growth promotion nitroimidazoles, clindamycin, cephalosporins Of special interest is the consumption of antibacterials intended for group or flock medication. When considering the risk for development of resistance, it is unimportant whether these medications take place by feed or water. data on formulations of antibacterials intended for such use have therefore been extracted from the data on total consumption shown in table 2.Va for the years 1993-1996. In table VI, some trends can be observed. The consumption of tetracyclines and quinoxalines has decreased sharply during the period. The usage of macrolides and streptogramins show only minor fluctuations. The pleuromutilins seem to have replaced the nitroimidazoles following the withdrawal from the market of the latter substances in 1995. Olaquindox is exclusively used in pigs. The only indication is diarrhoea around weaning but some off label use against swine dysentery is likely to occur. The usage of olaquindox was reduced by (total quantity of substance per number of pigs produced) from 1985 to 1987. Thereafter, however, more antibiotics were prescribed and the total amount used during the subsequent years 1988 and 1989 was 5 and , respectively, higher than in 1985 (Björnerot ET AL , 1996). Considering that the dosage prescribed in from 1986 and onwards was about three times higher than the dosage employed before, a smaller fraction of the weaning pigs was treated with olaquindox. Calculated this way, the proportion of pigs that were treated was in 1986 and in 1989 and in 1995 (Wierup, 1996). As mentioned, olaquindox is no longer available in . of formulations of antibacterials intended for treatment of animals through feed or water (flock or group medications) during 1993- 1996 expressed as kg substance 4ABELL 6) &¶RS¤LJNING AV BEREDNINGSFORMER AV ANTIBAKTERIELLA MEDEL AVSEDDA F¶R BEHANDLING VIA FODER ELLER VATTEN FLOCK ELLER GRUPPMEDICINERING UNDER UTTRYCKT SOM KG AKTIV SUBSTANS !4#VET CODE !CTIVE SUBSTANCE The combination of amprolium and ethopabate has been the drug of choice for prevention of coccidiosis in chickens intended for laying in . During the last few years, this product has been largely replaced by vaccination of replacement breeders. For broilers, a limited number of ionophores have been available to the during the past ten years. Narasin is, by far, the most widely applied product. The total usage of anticoccidials in feed has been calculated from the same sources as the antibacterials (see 2.6.1). Presently, approximately substance of coccidiostats is used annually in . The quantities in kg substance sold from 1980-1996 have then been calculated to medicated feed on basis of recommended dosages. For the year 1986, an apparent error in the reports to was discovered. Therefore, all figures for that year have been excluded. In figure 2, the results are compared with the number of broiler chickens produced in are shown in figure 2.I. 2.6.5Some comments on the Swedish consumption statistics The consumption statistics from show that the usage of antibacterials in animals can, and has been, reduced substantially. data are available on consumption statistics other than from the Nordic countries. Comparisons between countries are difficult, as no generally accepted method of correcting for differing numbers of animals of different species is available. The total numbers of animals in during 1988-1995 are presented in table 2.VII. As mentioned, figures on the total usage of antibacterial drugs should be interpreted with caution. Each substance group should be assessed separately, and knowledge on common indications is necessary in order to interpret the figures. In attempts to control resistance to antibacterials and to minimise the environmental impact of these drugs, monitoring systems for both usage of antibacterial drugs per animal species and for resistance to antibacterials in animal microbiota are crucial. Whenever undesirable trends are observed, activities to disclose underlying causes and, if possible, corrected. During the years 1980-1984, the consumption of tetracyclines in animals in increased markedly. Thereafter, the usage of these products decreased until 1988. From 1988-1993, an increase was again noted. The latter could not be connected to an altered disease situation, and therefore no obvious explanation was at hand. Further investigations into the precise origins of this were initiated in 1994 by . It was revealed that the increase could almost entirely be explained by the prescriptions of one veterinarian to one herd. The veterinarian was reported, the cause corrected, and the tetracycline consumption is now lower than before 1986. The comparison of statistics from different sources can also be a valuable asset. Results from the recently introduced system for statistics on prescriptions of medicated feed (Odensvik, 1997), were compared to data on sales from wholesalers and to data on sales of medicated feed reported by feed mills to . An excellent agreement between the different systems for statistics was found in question of antibacterial substances. However, for coccidiostats a major discrepancy was noted. The quantity covered by prescriptions in 1995 was about of the quantities registered in the two other systems. The amounts used, according to the latter, match well the number of chickens produced in that year (figure 2.I). Therefore, it can be assumed that one or more feed-mills have delivered coccidiostats without veterinary prescriptions. One such case has been identified and legal action has been taken. Usage of coccidiostats in expressed as quantity of medicated feed expressed as 1000 (left axis), and number of broiler chickens slaughtered in millions (right axis) &IGUR ) !NV¤NDNING AV KOCCIDIOSTATIKA I 3VERIGE UTTRYCKT SOM M¤NGD FODER UTTRYCKT SOM TAL TON MED TILLSATT L¤KEMEDEL V¤NSTER AXEL OCH ANTALET SLAKTADE SLAKTKYCKLINGAR I MILLIONER H¶GER AXEL The number of food- and fur-producing animals and horses in during 1988 to 1995 (from Björnerot, 1996) 4ABELL 6)) !NTAL LIVSMEDELSPRODUCERANDE DJUR P¤LSDJUR OCH H¤STAR I 3VERIGE UNDER FR¥N "J¶RNEROT Heifers, bulls, bullocks1 Pigs slaughtered2 (fattening) Horses2 (estimated figures) Minks5 (breeding females) Foxes5 (breeding females) Sources: 1Yearbook of Agricultural Statistics, 1989-1994. The numbers of individuals of different animal species are counted at a certain time (in ) every year, which means that the total numbers are not always included, for example calves born in the autumn that year are missing. Note, only animals on farms with more than 2.1 hectare land or in herds with at least 50 dairy cows or 250 cattle (bovines) or 250 pigs or 500 sheep (including lambs) or 1000 poultry (including chickens) are counted. 3Swedish , 4National , 5Swedish - estimated figures for 1994 and 1995. 2.7Prevalence of bacterial resistance Acquired resistance in bacteria to antibacterials is the results of reflects the exposure to the substances in question. Therefore statistics on prevalence of resistance in various bacterial species is an indirect way of assessing the consumption of antibacterials. Trends over time in prevalence of resistance among bacterial populations are likely to reflect quantities and patterns of usage. In accordance with the recommendations of WHO, antibiotic resistance in 3ALMONELLA spp. isolated from animals in has been monitored since Salmonellosis in animals is a notifiable disease in . All strains from animals isolated at or sent to are included. This surveillance is mainly motivated by the implications of resistant zoonotic bacteria for human health . Antibacterial resistance in 3ALMONELLA Typhimurium from animals in (Data from Franklin, 1997 unpublished and Franklin and Wierup, 1987; Franklin ET AL , 1994; Franklin, 1995) 4ABELL 6))) 2ESISTENS MOT ANTIBAKTERIELLA MEDEL HOS Salmonella 4YPHIMURIUM ISOLERADE FR¥N DJUR I 3VERIGE $ATA FROM &RANKLIN UNPUBLISHED AND &RANKLIN AND 7IERUP &RANKLIN ET AL &RANKLIN .O OF ISOLATES INVESTIGATED 1Breakpoint = value above which the isolate has been classified as resistant; 2 ND = not determined; 3 Isolated from a pigeon; 4 Isolated from a horse "RYTPUNKT V¤RDE ¶VER VILKEN ISOLATET BETECKNATS SOM RESISTENT .$ EJ UNDERS¶KT )SOLAERAD FR¥N EN DUVA )SOLERAD FR¥N EN H¤ST The antibiotic resistance in 3 Typhimurium in different time periods is shown in table 2.VIII. In the period 1978-1986, most strains were isolated from cattle. In 1988-1991 and 1992-1996, 43 and , respectively, of the isolates were of bovine origin. In the last period, were isolated from other sources than production animals, mostly wild birds. As apparent from the table, the number of resistant 3 Typhimurium has decreased since the surveillance programme was initiated. All investigated 3. Typhimurium strains and 3. strains isolated in 1988-1996 were sensitive to modern quinolones, trimethoprim-sulphonamides, neomycin and gentamicin, except one isolate of 3. Typhimurium from cattle which was resistant to trimethoprim-sulphonamides and one isolate of 3 Typhimurium from a horse that was resistant to modern quinolones. The low prevalence of resistant salmonellae can probably be ascribed to the fact that antibacterials are not used to eliminate salmonella infections in animals. The frequency of resistance in #AMPYLOBACTER JEJUNI isolated from chicken was investigated by (1996). Data on obtained minimum inhibitory concentrations () values are given in table 2.IX. Antibacterials are rarely used in broiler production in and the low proportion of resistant isolates seems to confirm the absence of a selective pressure. From other countries, quinolone resistance has been reported following the introduction of this drug (Endtz ET AL , 1991). Minimum inhibitory concentration () of antibacterials against 200 strains of #AMPYLOBACTER JEJUNI isolated from chickens in 4ABELL )8 -INSTA H¤MMANDE KONCENTRATION AV ANTIBAKTERIELLA MEDEL F¶R Campylobacter jejuni ISOLERADE FR¥N KYCKLINGFLOCKAR I 3VERIGE -INIMUM INHIBITORY CONCENTRATIONuG ML %SCHERICHIA COLI strains with ability to cause piglet diarrhoea and edema disease are among the most important intestinal pathogens in piglets. Weaning diarrhoea in pigs has also been associated with % COLI but the role of % COLI in that disease is not clear. In order to assess the development of resistance over time, three different investigations regarding antibiotic resistance in porcine % COLI were compared. The majority of the included strains originated from pig herds with diarrhoea problems. From table 2.X, it is apparent that the frequency of antibiotic resistant strains has not changed dramatically over the last ten years. The number of strains resistant to trimethoprim was unexpectedly high in 1981 to 1982 (), taking into account the fact that trimethoprim had only been used for 6 to 7 years in at that time.