sou · GLB3132d1 · 1998-01-01 00:00:00 — "RENNINKMEIYER # , 1996. The use of antimicrobials as growth promoters in poultry. )N PROCEEDINGS OF 88 7ORLDtS 0OULTRY #ONGRESS , . #ALDWELL * $ 5NDERDAHL . 2 AND 9OUNG ' ! Performance of primary SPF pigs on farms. *OURNAL OF !MERICAN 6ETERINARY !SSOCIATION 141-145. #%#, 1993. The impact of animal husbandry in Community of the use of growth promoters in animal feed. Volume 1 and 2.pp. Office for Official publications of Communities, , . #OATES - % 1980. 4HE GROWTH In: Growth in animals. $AVIS * 7 AND ,IBKE + ' , 1976. Bay VA 9391 for prevention of swine dysentery. 6ETERINARY -EDICINE AND 3MALL !NIMAL #LINICIAN 1257-1259. $E #RAENE ! AND 6IAENE * , 1992. Economic effects of technology in agriculture. Do performance enhancers for animals benefit consumers?pp. $EGR© - , 1996. Interferons and other cytokines in bacterial infections. *OURNAL OF )NTERFERON 2ESEARCH 417-426. Mode of action and effects %LWINGER + , 1976. Sammanställning över danska och svenska försök med tillväxtstimulerande ämnen (främst zinkbacitracin och payzone i foder till fjäderfä (report). %LWINGER + %NGSTR¶M " "ERNDTSON % &OSSUM / AND 4EGL¶F " , 1993. Effect of Avotan (avoparcin) and Maxus (avilamycin) on the caecal growth of #LOSTRIDIUM PERFRINGENS and the occurrence of necrotic enteritis in broilers (report). %LWINGER + %NGSTR¶M " "ERNDTSON % &OSSUM / AND 7ALDENSTEDT , , 1995. Effect of Maxus (avilamycin), Avotan (avoparcin), Monteban (narasin) and Elancoban (monensin-Na) on the caecal growth of #LOSTRIDIUM PERFRINGENS in broilers (report). %LWINGER + %NGSTR¶M " "ERNDTSON % &OSSUM / AND 7ALDENSTEDT , , 1996. Effect of growth promoters and coccidiostats on performance and growth of #LOSTRIDIUM PERFRINGENS in the caeca of broilers. )N PROCEEDINGS OF 88 7ORLD S 0OULTRY #ONGRESS 2-5 September, . %LWINGER + 3CHNEITZ # "ERNDTSON % &OSSUM / 4EGL¶F " AND %NGSR¶M " , Factors affecting the incidence of necrotic enteritis, caecal carriage of #LOSTRIDIUM PERFRINGENS and bird performance in broiler chickens. !CTA 6ETERINARIA 3CANDINAVICA 361-370. %LWINGER + AND 4EGL¶F " , 1991. Performance of broiler chickens as influenced by a dietary enzyme complex with and without antibiotic supplementation. !RCHIV FUR 'EFLUGELKUNDE 69-73. %YSSEN ( AND $E 3OMER 0 , 1967. Effects of 3TREPTOCOCCUS FAECALIS and a filterable agent in growth and nutrient absorption in gnotobiotic chicks. &LECK - + *ONES ' & 0OOMVISES 0 AND )NGKANINUN 0 , 1994. Porcine proliferative enteropathy outbreak and treatment using tylosin. )N PROCEEDINGS OFTH )063 #ONGRESS 26-30, . &ORBES - AND 0ARK * 9 , 1959. Growth of germ-free and conventional chicks. Effect of diet, dietary penicillin, and bacterial environment. *OURNAL OF .UTRITION 69-78. +VARNFORS % -¥NSSON ) AND 3IMONSSON ! Antibiotic additives in sows´ diet - effects on production and intestinal flora. !CTA !GRICULTURAE 3CANDINAVICA 273-285. &2 , 1992. History and development of probiotics. )N R. Fuller (ed. ), 0ROBIOTICS 4HE SCIENTIFIC BASIS , . &2 , 1994. Microbial activity in the alimentary tract of birds (domestic chicken, 'ALLUS DOMESTICUS). 0ROCEEDINGS OF THE .UTRITION 3OCIETY 55-61. '" , 1988. Mode of action and effects 'RUBER & , 1986. auf die Futteraufnahme beim Schwein. (Thesis). 'RUNFELD # :HAO # &* 0OLLOCK ! &RIEDMAN * AND &EINGOLD + 2 , 1996. Endotoxin and cytokines induce expression of leptin, the OB gene product in hamsters. #LINICAL )NVESTIGATION 2152-2156. Profylaktiska effekter av zinkoxid eller olaquindox mot avvänjningsdiarré hos svin. 3VENSK 6ETERIN¤RTIDNING 217-222. (UNNEMAN 7 ! From acute outbreaks to an almost subclinical situation. "ULLETIN DE L /FFICE )NTERNATIONAL DES %PIZOOTIES 915-923. *ACKS 4 - *UDITH & 2 &EIGHNER 3 $ AND ,IKOFF 2 / , 1986. 3-acetyl-4"-isovaleryl tylosin for prevention of swine dysentery. !MERICAN *OURNAL OF 6ETERINARY 2ESEARCH 2325-2328. *ANSSON , %LWINGER + %NGSTR¶M " &OSSUM / AND 4EGL¶F " , 1992. Clinical test of the efficacy of virginiamycin and dietary enzyme supplementation against necrotic enteritis (NE) infection in broilers.638. *ENKINS % - AND &$ , ))), 1985. Comparing carbadox and bacitracin in the prevention of clinical signs of swine dysentery. 6ETERINARY -EDICINE 90, 92-94. *ONASSON , AND !NDERSSON ( , 1996. Kartläggning av den svenska modellen - hävstång eller ok för svensk svinproduktion. *ORGENSEN " , 1987. Epidemiologiska analyser af sygdomsdata fra svinavelns forsøgsstationer. $ANSK 6ETERINAERTIDSKRIFT 209-219. *UKES 4 ( (ILL $ # AND "RANION ( $ , 1956. Effect of feeding antibiotics on the intestinal wall of the chick. 0OULTRY 3CIENCE 716-723. +LASING + # ,AURIN $ % 0ENG 2 + AND &$ - , 1987. mediated growth depression in chicks: Influence in feed intake, corticosterone and interleukine-1. *OURNAL OF .UTRITION 1629-1637. , AND *AMROZ $ , 1996. Effect of feeding antibiotic avoparcin on organ morphology in broiler chickens. 0OULTRY 3CIENCE 705-710. +RONSEDER ' , 1993. Wirkung und Verträglichkeit einer kohlenhydratspaltenden Enzympräparation (Roxazyme R G) in Broilerrationen. (Thesis). +YRIAKIS 3 # , 1989. The effects of avilamycin in the control of stress-induced post- weaning diarrhoea in piglets. *OURNAL OF 6ETERINARY 0HARMACOLOGY AND 4HERAPEUTICS 296-301. Mode of action and effects +YRIAKIS 3 # 4SINAS ! ,EKKAS 3 3ARRIS + AND "OURTZIHATZOPOULOU % , 1996a. Clinical evaluation of in feed zinc bacitracin for the control of porcine intestinal adenomatosis in growing/fattening pigs. 6ETERINARY 2ECORD 489-492. +YRIAKIS 3 # 4SINAS ! # ,EKKAS 3 3ARRIS + "OURTZI (ATZOPOULOU % "' AND *ANSEGERS , , 1996b. Clinical evaluation of in feed zinc bacitracin for the control of porcine intestinal adenomatosis in growing/fattening pigs. )N PROCEEDINGS OF TH )063 CONGRESS 7-10 , , . ,EV - AND &ORBES - , 1959. Growth response to dietary penicillin of germ-free chicks and of chicks with a defined intestinal flora. "RITISH *OURNAL OF .UTRITION 78-84. -AH© 9 AND /PPENHEIM * * 1992. )NTERLEUKIN In: Encyclopaedia of Immunology. Academic Press, . -C/RIST 3 , 1997. Use of oral antibiotics in farm livestock: facts and ethics. *OURNAL OF 6ETERINARY 0HARMACOLOGY AND 4HERAPEUTICS 3UPPL 175. -C/RIST 3 -ORGAN * &LECK 6EENHUIZEN - ,AWRENCE + AND +ROGER ( 7 , Oral administration of tylosin phosphate for treatment and prevention of proliferative enteropathy in pigs. !MERICAN *OURNAL OF 6ETERINARY 2ESEARCH 136- -EAD ' # , 1995. Role of probiotics in controlling foodborne pathogens in poultry. )N PROCEEDINGS OF TH %UROPEAN 3YMPOSIUM OF THE 7ORLDtS 0OULTRY 3CIENCE !SSOCIATION pp. -ILES 2 $ "ROWN 2 $ ## 7 AND /ELFKE % , 1996. Influence of an enzyme and an antibiotic on broiler performance. !PPLIED !NIMAL 2ESEARCH 105-117. -ILLER # 2 0HILIP * 2 &REE 3 - *R AND ,, - , 1972. Virginiamycin for prevention of swine dysentery. 6ETERINARY -EDICINE AND 3MALL !NIMAL #LINICIAN -OLNAR , AND -AGYAR + , 1987. Studies on the efficacy of Getroxel against 4REPONEMA HYODYSENTERIAE and its role in the control of swine dysentery. !CTA 6ETERINARIA (UNGARICA 405-413. -OORE ' - AND :IMMERMAN ! ' Efficacy of tylosin phosphate administered in feed for the prevention and control of porcine proliferative enteropathies in commercial swine herds. )N PROCEEDINGS OF TH )063 CONGRESS 7-10, -YERS $ * AND 3PEER 6 # , 1973. Effects of antibiotic and flushing on the performance of sows with short farrowing intervals. !NIMAL 3CIENCE 1125-1128. /LSON , $ , 1986. Probable elimination of swine dysentery after feeding ronidazole, carbadox or lincomycin and verification by feeding sodium arsanilate. #ANADIAN *OURNAL OF 6ETERINARY 2ESEARCH 365-368. 0RESCOTT * & AND "AGGOT * $ EDS , 1993. !NTIMICROBIAL THERAPY IN VETERINARY MEDICINE 2nd ed. Mode of action and effects 0RESCOTT * & 3IVENDRA 2 AND "ARNUM $ ! The use of bacitracin in the prevention and treatment of experimentally-induced necrotic enteritis in the chicken. #ANADIAN 6ETERINARY *OURNAL 181-183. 2AINIER 2 ( ($ , #2 $ +INYON * - AND "- ! Carbadox and lincomycin in the treatment and state control of swine dysentery 4REPONEMA HYODYSENTERIAE. !MERICAN *OURNAL OF 6ETERINARY 2ESEARCH 2AINIER 2 ( ($ , '2 $ +INYON * - AND "- ! Prevalence of asymptomatic of swine dysentery following withdrawal of carbadox or lincomycin treatments. )N PROCEEDINGS OF TH )063 #ONGRESS 30- 2AYNAUD * 0 AND "RETHEAU ( , 1973. Essais a large echelle du carbadox dans les elevages porcins en . Bilan en 1972. 2EVUE DE MEDICINE 6ETERINAIRE 2AYNAUD * 0 "RUNAULT ' AND 0ATTERSON % " , 1980a. A new swine dysentery model for evaluation of drug prophylaxis: I. Model development - oral infection plus pen contamination. )N PROCEEDINGS OF TH )063 #ONGRESS 30 , 2AYNAUD * 0 "RUNAULT ' AND 0ATTERSON % " , 1980b. A new swine dysentery model for evaluation of drug prophylaxis: II. Efficacy of various drugs in the control of swine dysentery. )N PROCEEDINGS OF TH )063 #ONGRESS 30 , 2OBERTSSON * AND ,UNDEHEIM . Prohibited use of antibiotics as a feed additive for growth promotion - effect on piglet health and production parameters. )N PROCEEDINGS OF TH )063 #ONGRESS 26-30, . 2ONNE ( AND *ENSEN * # % , 1992. Virginiamycin susceptibility of 3ERPULINA HYODYSENTERIAE, IN . 6ETERINARY 2ECORD 239-240. 2OSEN ' $ 1995. !NTIBACTERIALS IN POULTRY AND PIG NUTRITION In: Biotechnology in Animal Feeds and Feeding. VCH Verlagsgesellschaft mbH, Weinheim. 2OSEN ' $ , 1996. The nutritional effects of tetracyclines in broiler feeds. )N PROCEEDINGS OF 88 7ORLDtS 0OULTRY #ONGRESS . 2OURA % (OMEDES * AND +LASING + # , 1992. Prevention of immunologic stress contributes to the growth-permitting ability of dietary antibiotics in chicks. *OURNAL OF .UTRITION 2383-2390. 3#", 1997. Jordbruksstatistisk årsbok 1996. pp. 3CHNEIDER 7 , 1992. Wirkung des Futterzusatztsoffes G in der Schweinemast. 3CHWEINESUCHT UND 3CHWEINEMAST 118-121. Mode of action and effects 3,5 +ONTAKT, 1996. Områdeskalkyler för slaktsvin, smågrisproduktion, värphöns och slaktkyckling. AND 3PEER 6 # , 1975. Effects of PMS and chlortetracycline on the reproductive efficiency of sows. !NIMAL 3CIENCE 100-105. 3PEER 6 # , 1974. Reducing farrowing intervals in sows. &EEDSTUFFS 20-31. 3TAHLY 4 , 1996. Impact of immune system activation on growth and optimal dietary regimens of pigs. )N Gansworthy. ), 2ECENT ADVANCES IN ANIMAL NUTRITION 3TAHLY 4 3 7ILLIAMS . ( AND 3WENSON 3 ' , 1996. Impact of carbadox on rate, efficiency and composition of growth in pigs with a high or low genetic capacity for lean growth. )N PROCEEDINGS OF TH )063 #ONGRESS 7-10 , . 3TAHLY 4 3 7ILLIAMS . ( AND :IMMERMANN $ 2 , 1995. Impact of tylosin on rate, efficiency and composition of growth in pigs with a low or high level of immune system activation. *OURNAL OF !NIMAL 3CIENCE SUPPLEMENT 84. 3TUTZ - 7 *OHNSON 3 , AND *UDITH & 2 , 1983a. Effects of diet and bacitracin on growth, feed efficiency, and populations of #LOSTRIDIUM PERFRINGENS in the intestine of broiler chicks. 0OULTRY 3CIENCE 1619-1625. 3TUTZ - 7 *OHNSON 3 , *UDITH & 2 AND -UIR , ! Effect of the antibiotic thiopeptin on #LOSTRIDIUM PERFRINGENS and growth and feed efficiency of broiler chicks. 0OULTRY 3CIENCE 1633-1638. 4AYLOR $ * AND $AVEY , ! Elimination of 4REPONEMA HYODYSENTERIAE infection from pigs by medication with carbadox. )N PROCEEDINGS OF TH )063 #ONGRESS 30- 3, . 4HOMKE 3 AND %LWINGER + , 1997a. Alternatives to antibiotic growth promotants. Report to to Commission on Antimicrobial Feed Additives. 4HOMKE 3 AND %LWINGER + , 1997b. Growth and feed efficiency responses to antibiotic growth promotants in pigs and poultry. Report to the Commission on Antimicrobial Feed Additives. 4HOMKE 3 AND %LWINGER + , 1997c. Mode of action of antibiotic growth promotants. Report to the Commission on Antimicrobial Feed Additives. 4ROUTT ( & (OOPER " % AND (ARRINGTON 2 , 1974. Effect of carbadox in experimentally induced salmonellosis of swine. *OURNAL OF THE !MERICAN 6ETERINARY -EDICAL !SSOCIATION 402-404. 7ALLGREN 0 , 1993a. Infections and immune functions of swine in fattening herds. (Thesis). Mode of action and effects 7ALLGREN 0 , 1993b. Infektioners inflytande på tillväxthastigheten hos svin. 3VENSK 6ETERIN¤RTIDNING 727-732. 6%4 & 1997. &!33 6%4 3WEDISH (Drug information service of pharmaceutical companies in ), . 6IAENE * , 1997. The Swedish animal production system. Could it be applied across Union. 7ICKER $ , )SGRIGG 7 . AND 4RAMMEL * ( , 1977. The control and prevention of necrotic enteritis in broilers with zinc bacitracin. 0OULTRY 3CIENCE 1229-1231. 7IERUP - , 1996. förbjöd antibiotika i tillväxtbefrämjande syfte 1986 - vad hände med djurhälsan och hur löstes problemen? +UNGLIGA 3KOGS OCH ,ANTBRUKSAKADEMIENS 4IDSKRIFT 69-78. 7ILLIAMS " * AND "ABCOCK , 1978. )N 6IVO and )N 6ITRO susceptibility of 4REPONEMA HYODYSENTERIAE to carbadox before and after repeated in vitro passage in sublethal concentrations of drug. 6ETERINARY -EDICINE AND 3MALL !NIMAL #LINICIAN 432-433, 436. 7ILLIAMS " * AND 3HIVELY * % , 1978. )N 6ITRO antitreponemal activities of carbadox, virginiamycin, olaquindox, and tylosin as of their effectiveness for preventing swine dysentery. 6ETERINARY -EDICINE AND 3MALL !NIMAL #LINICIAN Financial aspects of swine dysentery eradication without depopulation. )N PROCEEDINGS OF TH )063 #ONGRESS . 6RANJES - 6 AND 7ENK # , 1996. Influence of 4RICHODERMA VIRIDAE enzyme complex on nutrient utilization and performance of laying hens in diets with and without antibiotic supplementation. 0OULTRY 3CIENCE 551-555. 5NDERDAHL , * 3UMPTON , * 0EO , 3 /LSEN ' 7 +ELLY $ " (UDMAN $ " #ALDWELL * $ AND !DAMS # ( , 1959. Performance within a "disease-free" experiment station herd. *OURNAL OF !MERICAN 6ETERINARY !SSOCIATION 491-496. 4Microbiological aspects on antibacterial feed additives Antibacterial substances (antibiotics and synthetic substances) exert their activity by inhibiting or disturbing vital bacterial processes. The effect is concentration dependent. At levels above the minimum inhibitory concentration (), bacterial growth will cease or the bacteria will be killed. The only way for sensitive bacteria to avoid elimination is to develop resistance. This can be achieved by mutation or by acquisition of genes from other bacteria. Transfer of genes occurs by several mechanisms, namely transduction, transformation, and conjugation mediated by plasmids and/or transposons. The latter mechanism is the most studied and possibly the most important. Horizontal gene transfer between bacteria is a common event and an important factor in microbial evolution. Antimicrobial resistance, leading to loss of effectiveness of antibacterial drugs, has been targeted by the WHO as one of the major emerging human health problems (WHO, 1994). The consequences of antimicrobial resistance are seen as an increase in morbidity and mortality due to bacterial diseases. Antimicrobial resistance also has a considerable economic impact and is estimated to cost at least US$ 4 billion annually in the alone. The possible influence of antibacterial feed additives () on resistance in animal and human pathogens has been debated for almost four decades. The development of new techniques, particularly in the field of molecular biology, has provided new insights into these problems. The antibacterial effect of is also manifested in alterations of the intestinal microflora. The intact microflora is an important barrier against colonisation by enteric pathogens. Disruptions may lead to increased prevalence of zoonotic bacteria in food. At the end of this chapter, a short glossary of terms used has been provided. The concentrations of used in feed for performance enhancement exceed the susceptibility ranges of naturally susceptible intestinal bacteria (table 4.I). Concentrations reached in various parts of the intestine using the approved dosages will depend on a number of factors. Most are poorly, if at all, absorbed from the gut. They are therefore likely to be present in concentrations well above the of normally susceptible bacterial species at least in part of the intestine. The fact that exert an inhibitory effect on the intestinal microflora is evident from various types of experiments. studies showed that the growth promoting effect could be associated with changes in the microflora, especially the enterococci and the clostridia, of the animals (see chapter 3.1). This is further substantiated by the preventive effect of against certain intestinal diseases (see chapter 3.2). For therapy, higher doses are generally needed. By definition, therapy will be instituted once the disease is overt. When the infectious agent to be combated is already established in tissues, higher doses will be needed in order to have a satisfactory effect. If the infectious process is located in an internal organ other than the intestine, the administered substance must reach this organ at concentrations well above . As the amount of substance given will then have to be absorbed in adequate amounts and be distributed in a larger volume (the whole body as opposed to only the intestine), higher doses are needed. Normal susceptibility ranges of clostridia and enterococci for some compared to permitted levels in feed for performance enhancement (modified from Dutta and Devriese, 1984; Devriese ET AL , 1993) 4ABELL ) +¤NSLIGHET HOS KLOSTRIDIER OCH ENTEROKOCKER F¶R N¥GRA !&4 J¤MF¶RT MED TILL¥TNA HALTER I FODER F¶R AVKASTNINGS¶KNING MODIFIERAT FR¥N $UTTA AND $EVRIESE $EVRIESE ET AL 2ANGE OF MINIMUM INHIBITORY 1 NA = no information available; 2Given in IU/ml INFORMATION SAKNAS 5TTRYCKT I )% ML The mechanisms of action of the different types of substances used as have been studied in detail, with the exception of the quinoxalines. Currently approved exert their effect on bacteria by one of four mechanisms (table 4.II): ·inhibition of protein synthesis ·inhibition of cell wall synthesis ·inhibition of DNA synthesis ·alterations of the cytoplasmic membrane Concerning information on resistance mechanisms and their genetic background, practically all published studies on resistance mechanisms have focused on substances, or , also used in human therapy and mostly on resistance in human pathogens. The characterised resistance genes and mechanisms are probably only the tip of the iceberg. It is often stated that the used in animal production are not used as therapeuticals in humans. This is true only for avilamycin, flavomycin and the quinoxalines. Spiramycin is used in human therapy. So is bacitracin, although mainly for local application. Small chemical differences between substances within the same class of antibacterials may have profound effects on their pharmacokinetics but their mode of action on the bacterium will usually be the same. Therefore, the bacterial defence in the form of resistance will often confer cross-resistance to all or most substances of the same class. Tylosin, avoparcin, ardacin and virginiamycin all belong to of antibacterials that include valuable therapeuticals. , presently not used substances may become valuable therapeuticals in the future. Such is the case with everninomycins, a substance of the orthosomycin class. This substance is presently undergoing trials as a new drug candidate. Another member of the orthosomycin class is avilamycin. Most are similar to, or identical with, antibacterials used for therapy. are, in concentrations given for performance enhancement, inhibitory to inherently susceptible intestinal bacteria. 4.3AFA and development of resistance It has been argued that the concentrations of antibacterials used for performance enhancement are too low for any development of resistance to occur. As noted in 4.2, they are high enough to inhibit the growth of susceptible microorganisms. The usage of would therefore be expected to favour the occurrence of resistant strains in exposed populations. Mode of action of substances used as and known mechanisms of resistance (modified from , 1996) 4ABELL )) 6ERKNINGSMEKANISMER HOS SUBSTANSER SOM ANV¤NDS SOM !&4 OCH K¤NDA RESISTENSMEKANISMER MODIFIERAD FR¥N 7ITTE inhibition of cell wall modification of binding site (peptidoglycan precursor) modification of binding site synthesis by stalling the (methylation of 23S rRNA) drug inactivation, efflux inhibition of cell wall inhibition of cell wall efflux, alteration of BCR gene, BACA gene binding site (IPP), reduced modification of binding site , SAT VAT, VGA SBH synthesis by stalling the (methylation of 23S rRNA), Substances with well known therapeutic use in human and/or veterinary medicine are in bold characters. 3UBSTANSER MED V¤LK¤NDA TERAPEUTISKA APPLIKATIONER INOM HUMAN OCH ELLER VETERIN¤RMEDICINEN ¤R SKRIVNA MED FETSTIL Several studies by the research group of (Hinton ET AL , 1986b; Kaukas ET AL , 1987; Kaukas ET AL , 1988) illustrate the influence of on development of resistance in enterococci. In two of these studies (Hinton ET AL , 1986b; Kaukas ET AL , 1987), the control groups were given a diet containing growth promoters (bacitracin or virginiamycin) and/or a coccidiostat with antibacterial activity. The confounding effect of growth promoters and anticoccidials in the control groups of these latter studies cannot be ignored. Consequently, only comparisons between the groups in the study from 1988 are deemed to be valid and will, in the following, be discussed in detail. In this study (Kaukas ET AL , 1988), small groups of chickens were given feed containing either avoparcin, nitrovin, virginiamycin or bacitracin or a diet without during the first three weeks of life. The resistance to virginiamycin, bacitracin or nitrovin in % FAECIUM increased in the groups receiving the respective substance. Moreover, the incidence of resistance to therapeutic antibiotics, expressed as Antibiotic Resistance Index (), was higher (p=0.003) in all groups receiving antibacterials. This increase could be associated with an increase in the proportion of % FAECIUM in the enterococcal population of the treated birds. An experimental study on germ-free mice fed carbadox, olaquindox, flavomycin and chlortetracycline was reported by Corpet (1984). The mice were inoculated with intestinal microflora from 4 piglets, and the drugs were given at dosages corresponding to those used for growth promotion in livestock. effect on coliform resistance against olaquindox and carbadox was observed, while resistance against tetracycline increased in the flora of mice fed this drug. In the group given flavomycin, resistance to tetracycline was lower than in the control group. Resistance against flavomycin was not tested. and Moeller (1977a) investigated the effect of in-feed flavomycin on the antibacterial susceptibility patterns of faecal % COLI from calves. They found an increase in resistance to flavomycin, but a decrease in resistance against streptomycin and tetracycline in the medicated group. Observations on an apparent suppression of coliforms carrying resistance plasmids has been suggested in reports for both flavomycin, carbadox and bacitracin (, 1975; , 1978; Sepulchre, 1979; Gedek, 1981; , 1984; and Wheeler, 1987; Brophy, 1988). Some of these reports, however, merely studied the synergistic effects of the and other antibacterials and in others, the information provided is not enough to fully evaluate the issue. Only for flavomycin have the possible mechanisms for a direct effect on numbers of plasmid carrying strains been addressed. and co-workers (1984) investigated several possible mechanisms for the effects of flavomycin in concentrations from 1-4 ppm on % COLI strains harbouring different types of plasmids. The growth of some, but not all, of the plasmid carrying strains was inhibited in the presence of flavomycin. The plasmid transfer rates were mostly reduced, but also in some cases increased, depending on the type of plasmid. The authors suggest, among other explanations, that the differences observed could be due to flavomycin interacting with transfer-related cell wall structures, such as pili, coded for by certain plasmids.