sou · GLB3132d3 · 1998-01-01 00:00:00 — One cannot be certain that the proportion of coliforms mistakenly identified as salmonellae would be the same in all experimental groups. The major objection against the design of this study, however, is that all birds also received 100 ppm monensin. Since monensin has antibacterial effects, this must be regarded as a possible confounder. Thus, the study only investigated the differences between birds fed monensin and birds fed monensin plus avoparcin or virginiamycin. Another study by and co-workers (, 1983) reported no significant difference between avoparcin-fed birds and control birds, regarding salmonella shedding after experimental infection. On the other hand the prevalence among birds raised on clean was significantly higher that that among birds raised on used . and co-workers (1985) and Hinton and co-workers (1986) reported two salmonella studies that include avoparcin. The birds were naturally infected via contaminated food, and all animals, except for one control group in one experiment, also received monensin. This makes the results difficult to evaluate, but in the first study the authors stated that there was no statistical difference between the medicated group and the control group (, 1985) and in the other that the results were inconclusive (Hinton ET AL , 1986). In 1989, (1989) demonstrated a dose-response relationship between in-feed avoparcin and prevalence of salmonella shedding among experimentally infected chickens. Infections with 3. Typhimurium, 3. Choleraesuis, 3. Arizonae all gave similar results. This is the only published study on dose-response relations between and salmonella shedding. It provides an explanation to why some studies yield contradictory results; the concentrations of avoparcin used in most studies (around 10 ppm) appear to correspond roughly to the breakpoint of response- no response. and co-workers (1991) investigated the effects of various , including avoparcin, on salmonella shedding among CE- (competitive exclusion) treated chickens. The authors stated that birds fed 10 ppm avoparcin had significantly more salmonella in their caeca than control birds receiving no antibiotic. However the concurrent CE-treatment, among other things, make these results hard to evaluate. In conclusion, avoparcin increases the prevalence of salmonella shedding among experimentally infected chickens, as demonstrated by a dose-response relationship. Avoparcin also lowers the infectious dose necessary for achieving salmonella colonisation of chickens. No studies have been found regarding ardacin, but as the two substances are very similar in activity and antibacterial spectrum, there is no reason to believe that ardacin would differ from avoparcin in this respect. D.7.2 Other enteric pathogens No publications have been found on the influence of either avoparcin or ardacin on the intestinal colonisation of target animals with other zoonotic pathogens. Glycopeptides are poorly absorbed after oral ingestion (Prescott and Baggot, 1993). In an experiment where radiolabelled avoparcin was fed to chickens for 7 consecutive days at the dose of /kg body weight, virtually the entire dose was retrieved in urine-faecal samples and in gastrointestinal contents (Zulalian ET AL , 1979). Residues in all tissues were less than 0.05 ppm. Based on these findings, the authors concluded that essentially no avoparcin was absorbed from the gastrointestinal tract of the animals. No residues are therefore to be expected. Maximum residue levels (MRL) have not been established. Experimental feeding of broiler chickens with 15 ppm ardacin for 30 days resulted in liver residues of up to /kg after a 7 day withdrawal period (Gottschall ET AL , 1995). Ardacin is not biotransformed to any large extent (Gottschall ET AL , 1995). No MRL has been established. No information on toxicity to target species, non-target species or humans has been found. Vancomycin is ototoxic in humans, but it is not known whether this feature is shared by ardacin or avoparcin. Occupationally derived contact dermatitis after contact with avoparcin has been reported (Barriga ET AL , 1992). As for other , if feeding avoparcin or ardacin leads to a reduction in the amount of feed consumed per kg weight gain, this would be expected to lead to a reduction in nitrogen output. Like other naturally produced antibiotics, avoparcin and ardacin would be expected to be microbially degraded in soil, but no reports relating to the environmental fate of either ardacin or avoparcin have been found. Regarding avoparcin, that has been used for over 20 years in some countries, it is remarkable that such information is not publicly available. Increased glycopeptide resistance is a human health problem. Avoparcin has been shown to select for glycopeptide resistance among animal bacteria, and there is no reason to believe that ardacin would be any different in this respect. Numerous reports indicate that transfer of glycopeptide resistance between animal and human microflora can and does occur. Avoparcin has also been shown to affect salmonella colonisation. The lowering of the infectious dose necessary for colonisation that is seen in avoparcin-treated animals indicate that avoparcin may increase the prevalence of salmonella-infected poultry flocks, especially in areas where the exposure to salmonella is low. The available information on toxicological and environmental aspects is too scarce to form the basis of any assessment. !ARESTRUP & - , 1995. Occurence of glycopeptide resistance among %NTEROCOCCUS FAECIUM isolates from conventional and ecological poultry farms. -ICROBIAL $RUG 2ESISATNCE 255-257. % AND (OBBS * . *R , 1995. Induction of vancomycin resistance in Enterococcus faecium by non-glycopeptide antibiotics. &%-3 -ICROBIOLOGY ,ETTERS !RTHUR - AND #OURVALIN 0 , 1993. Genetics and mechanisms of glycopeptide resistance in enterococci. !NTIMICROBIAL !GENTS AND #HEMOTHERAPY 1563-1571. !RTHUR - $EPARDIEU & 'ERBAUD ' 'ALIMAND - ,ECLERCQ 2 AND #OURVALIN 0 , 1997. The VanS sensor negatively controls VanR-mediated transcriptional activation of glycopeptide resistance genes Tn1546 and related elements in the absence of induction. *OURNAL OF "ACTERIOLOGY 97-106. !RTHUR - -OLINAS & $EPARDIEU & AND #OURVALIN 0 , 1993. Tn , a Tn related transposon conferring glycopeptide resistance by synthesis of depsipeptide precursors in %NTEROCOCCUS FAECIUM BM4147. *OURNAL OF "ACTERIOLOGY !RTHUR - 2EYNOLDS 0 AND #OURVALIN 0 , 1996. Glycopeptide resistance in enterococci. 4RENDS IN -ICROBIOLOGY 401-407. "-ADSEN - #HRISTENSEN * AND !ARESTRUP & - , 1997. a growth promoter is associated with the occurrence of vancomycin-resistant %NTEROCOCCUS FACECIUM on Danish poultry and pig farms. 0REVENTIVE 6ETERINARY -EDICINE 95-112. "APTISTA M $EPARDIEU & #OURVALIN 0 AND !RTHUR - , 1996. Specificity of induction of glycopeptide resistance genes in Enterococcus faecalis. !NTIMICROBIAL AGENTS AND CHEMOTHERAPY 2291-2295. 2OMAGUERA # AND 6ILAPLANA * , 1992. Contact dermatitis from avoparcin. #ONTACT $ERMATITIS 115. "ARROW 0 ! Further observations on the effect of feeding diets containing avoparcin on the excretion of salmonellas by experimentally infected chickens. %PIDEMIOLOGY AND )NFECTION 239-252. "ATES * *ORDENS * : AND 'RIFFITHS $ 4 , 1994. Farm animals as a putative reservoir for vancomycin-resistant enterococcal infection in man. *OURNAL OF !NTIMICROBIAL #HEMOTHERAPY 507-516. #HADWICK 0 2 7OODFORD . +ACZMARSKI % " '3 "ARRELL 2 ! AND /PPENHEIM " ! Glycopeptide-resistant enterococci isolated from uncooked meat. *OURNAL OF !NTIMICROBIAL #HEMOTHERAPY 908-909. #OQUE 4 - 4OMAYKO * & 2ICKE 3 # /KHYUSEN 0 # AND -URRAY " % , 1996. Vancomycin-resistant enterococci from nosocomial, community, and animal sources in the . !NTIMICROBIAL !GENTS AND #HEMOTHERAPY 2605-2609. $!.-!0, 1997. Consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in . )EVEN - 'OOSSENS ( 6ANDAMME 0 0OT " (OMMEZ * AND (AESEBROUCK & , 1996. Presence of vancomycin-resistant enterococci in farm and pet animals. !NTIMICROBIAL !GENTS AND #HEMOTHERAPY 2285-2287. AND $EVRIESE , ! Susceptibility of fecal streptococci of poultry origin to nine growth-promoting agents. !PPLIED AND %NVIRONMENTAL -ICROBIOLOGY %DMOND - " /BER * & 7EINBAUM * , 0FALLER - ! (4 AND 3ANFORD - $ , 1995. Vancomycin-resistant %NTEROCOCCUS FAECIUM bacteriemia: risk factors for infection. #LINICAL )NFECTIOUS $ISEASES 1126-1133. %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, . %VERS 3 AND #OURVALIN 0 , 1996. Regulation of VanB-type vancomycin resistance gene expresion by the VanSB-VanRB two-component regulatory system in Enterococcus faecalis V583. *OURNAL OF "ACTERIOLOGY 1302-1309. 'ORDTS " ,ANDUYT ( )EVEN - 6ANDAMME 0 AND 'OOSENS ( , 1995. Vancomycin-resistant enterococci colonizing the intestinal tracts of hospitalized patients. *OURNAL OF #LINICAL -ICROBIOLOGY 2842-2846. 'OTTSCHALL $ 7 &ILTER - , AND 7ANG 2 , 1995. Analysis of tissue residues and comparative metabolism of ardacin in cattle, broilers, and rats. *OURNAL OF !GRICULTURAL AND &OOD #HEMISTRY 2956-2963. 'REEN - 3HLAES * ( "ARBADORA + AND 3HLAES $ - , 1995. Bacteriemia due to vancomycin-dependent %NTEROCOCCUS FAECIUM. #LINICAL )NFECTIOUS $ISEASES 712- '# , 1996. Inventering av resistens mot antibakteriella medel hos enterokocker från kyckling (rapport). 'USTAFSON 2 ( , 1983. Salmonella shedding and feed additives. )N PROCEEDINGS OF TH )NTERNATIONAL 3YMPOSIUM ON !NTIBIOTICS IN !GRICULTURE "ENEFITS AND -ALEFITS Butterworths,Nottingham. 'USTAFSON 2 ( "ECK * 2 AND +OBLAND * $ , 1981. The influence of Avoparcin on the of Salmonella in chickens. :ENTRALBLATT FUR 6ETERIN¤RMEDIZIN 2EIHE " 119-128. (AAHEIM ( 3IMONSEN ' 3 $AHL + ( ,OVESETH ! /LSVIK / +RUSE ( AND 3UNDSFJORD ! 6ANA glycopeptide resistant enterococci: Identical VANA gene cluster in glycopeptide resistant enterococi from man and avoparcin-exposed poultry. )N PROCEEDINGS OF TH )NTERNATIONAL -EETING ON "ACTERIAL %PIDEMIOLOGICAL -ARKERS , , . (ANDWERGER 3 3KOBLE * $ISCOTTO , & AND 0UCCI - * , 1995. VANA gene cluster in clinical isolates of enterococci from the northeastern . !NTIMICROBIAL !GENTS AND #HEMOTHERAPY 362-368. (AYDEN - + 0ICKEN 2 . AND 3AHM $ & , 1997. glycopeptide resistance in enterococci associated with transfer of VANB. !NTIMICROBIAL !GENTS AND #HEMOTHERAPY 872-874. (AYDEN - + 4REHOLME * % 3CHULTZ * % AND 3AHM $ & , 1993. )N VIVO development of teicoplanin resistance in a VANB %NTEROCOCCUS FAECIUM isolate. *OURNAL OF )NFECTIOUS $ISEASES 1224-1227. ()#0!#, 1995. Recommendations for preventing the spread of vancomycin resistance: recommeendations of the Hospital Infection Control Practices Advisory Committe (HICPAC). !MERICAN *OURNAL OF )NFECTION #ONTROL 87-94. (INTON - !L #HALABY : ! - AND ,INTON ! ( , 1986. The influence of dietary protein and antimicrobial feed additives on salmonella carriage by broiler chickens. 6ETERINARY 2ECORD 495-500. Hudd, D.L., 1983. The addition of antibiotics to feedingstuffs. In : Pharmacological basis of large animal medicine. Eds Lees, J.A.B.P., Yoxall, A.T. Balckwell Scientific Publications, , UK. (,ALANDE & L (OSPITALIER 2 3ALVAT ' AND "ENNEJEAN ' , 1991. of four antibiotic additives on the Salmonella contamination of chicks protected by an adult caecal flora. !VIAN 0ATHOLOGY 577-584. *ENSEN , " , 1996. Characterization of the VANA gene cluster in vancomycin resistant %NTEROCOCCUS FAECIUM (preliminary report 06-11-96). *ORDENS * : "ATES * AND 'RIFFITHS $ 4 , 1994. Faecal carriage and nosocomial spread of vancomycin resistant %NTEROCOCCUS FAECIUM. *OURNAL OF !NTIMICROBIAL #HEMOTHERAPY. (INTON - AND ,INTON ! ( , 1988. The effect of growth-promoting antibiotics on the faecal enterococci of healthy young chickens. *OURNAL OF !PPLIED "ACTERIOLOGY 57-64. +IRK - #HEN ( 9 (ILL 2 #ASEWELL - 7 AND "EIGHTON $ , 1997. Novel insertion sequences from vancomycin-resistant%NTEROCOCCUS FAECIUM isolated from poultry. )N PROCEEDINGS OF TH )#! +LARE ) (( #LAUS ( "¶HME ' -3 3ELTMANN ' (AKENBECK 2 !NTANASSOVA 6 AND 7ITTE 7 , 1995a. %NTEROCOCCUS FAECIUM strains with VANA- mediated high level glycopeptide resistance isolated from animal food-stuffs and faecal samples of humans in the community. -ICROBIAL $RUG 2ESISATANCE 265- +LARE ) (( #LAUS ( 2EISSBRODT 2 AND 7ITTE 7 , 1995b. VANA-mediated high-level glycopeptide resistance in %NTEROCOCCUS FAECIUM from animal husbandry. &%-3 -ICROBIOLOGY LETTERS 165-172. +RUSE ( , 1995. The use of avoparcin as a feed additive and the occurrence of vancomycin resistant %NTEROCOCCUS spp. in poultry production (report). ,ECLERCQ 2 $ERLOT % 7EBER - $UVAL * AND #OURVALIN 0 , 1989. Transferable vancomycin and teicoplanin resistance in %NTEROCOCCUS FAECIUM. !NTIMICROBIAL !GENTS AND #HEMOTHERAPY 10-15. ,ECLERQ 2 , 1997. Enterococci acquire new kinds of resistance. #LINICAL )NFECTIOUS $ISEASES SUPPL S80-S84. ,EUCHTENBERGER 7 ' , 1981. Einfluss antibiotischer Futterzusatze auf die und auf die Persistenz von 3ALMONELLA TYPHIMURIUM Infektionen. (Thesis). Tierärztliche Hochschule, . ,INDEN P + 0ASCULLE ! 7 -ANEZ 2 +RAMER $ * &UNG * * 0INNA ! $ AND +USNE 3 , 1996. Differencies in outcome for patients with bacteriemia due to vancomycin resistant faecium of vancomycin susceptible Enterococcus faecium. #LINICAL )NFECTIOUS $ISEASES 663-670. ( !L #HALABY : ! - AND (INTON - ( , 1985. salmonella infection in chickens: a potential model for testing the effects of various procedures on salmonella shedding. 6ETERINARY 2ECORD 361-364. -ACKINNON - ! AND 4YRRELL ' * , 1997. characterization of IS , an insertion sequence-like element that disrupts VanY function in a vancomycin-resistant %NTEROCOCCUS FAECIUM strain. !NTIMICROBIAL !GENTS AND #HEMOTHERAPY 1805-1807. -URRAY " % , 1990. The life and times of the Enterococcus. #LINICAL -ICROBIOLOGY 2EVIEWS 46-65. .OBLE 7 # 6IRANI : AND #REE 2 ' , 1992. Co-transfer of vancomycin and other resistance genes from %NTEROCOCCUS FAECALIS NCTC 12201 to 3TAPHYLOCOCCUS AUREUS. &%-3 -ICROBIOLY ,ETTERS 195-198. 0ANAGEA 3 AND #HADWICK 0 2 , 1996. Heat tolerance of vancomycin resistant *OURNAL OF #LINICAL 0ATHOLOGY 687-689. 0ERICHON " 2EYNOLDS 0 AND #OURVALIN 0 , 1997. %NTEROCOCCUS FAECIUM BM 4339. !NTIMICROBIAL !GENTS AND #HEMOTHERAPY 0OWER % ' - !BDULLA 9 ( 4ALSANIA ( ' 3PICE 7 !ATHITHAN 3 AND &RENCH ' , , 1995. VANA genes in vancomycin-resistant clinical isolates of /ERSKOVIA TURBATA and !RCHANOBACTERIUM #ORYNEBACTERIUM HAEMOLYTICUM. *OURNAL OF !NTIMICROBIAL #HEMOTHERAPY 595-606. 0OYART # 0IERRE # 1UESNE ' 0RON " "ERCHE 0 AND 4RIEU #UOT 0 , 1997. Emergence of vancomycin resistance in the genus 3TREPTOCOCCUS: characterisation of a VANB transferable determinant in 3TREPTOCOCCUS . !NTIMICROBIAL !GENTS AND #HEMOTHERAPY 24-29. 0RESCOTT * & , 1979. The prevention of experimentally induced necrotic enteritis in chickens by avoparcin. !VIAN $ISESES 1072-1074. 0RESCOTT * & AND "AGGOT * $ EDS , 1993. !NTIMICROBIAL THERAPY IN VETERINARY MEDICINE 2nd ed. 1UINTILIANI 2 * AND #OURVALIN 0 , 1994. Conjugal transfer of the vancomycin resistance determinant VANB between enterococci is associated with the movement of large elements from chromosome to chromosome. &%-3 -ICROBIOLOGY ,ETTERS 1UINTILIANI 2 * AND #OURVALIN 0 , 1996. Charachterization of Tn , a composite transposon flanked by the IS and IS -like elements, that confers vancomycin resistance in %NTEROCOCCUS FAECALIS BM4281. 2EYNOLDS 0 , 1990. Glycopeptide antibiotics: Pharmacokinetics, spectrum of activity, resistance patterns. (OSPITAL &ORMULARY 537-544. 3MITH ( 7 AND 4UCKER * & , 1978. The effect of antimicrobial feed additives on the colonization of the alimentary tract of chickens by 3ALMONELLA TYPHIMURIUM. *OURNAL OF (YGIENE 217-231. 3MITH 7 ( AND 4UCKER * & , 1980. Further observations on the effect of feeding diets containing avoparcin, bacitracin and sodium arsenilate on the colonization of the alimentary tract of poultry by salmonella organisms. *OURNAL OF (YGIENE 137- 4ORRES # 2EGUERA * ! 3ANMARTIN M * 0EREZ $IAZ * # AND "AQUERO & , 1994. VAN-A mediated vancomycin-resistant %NTEROCOCCUS spp in sewage. *OURNAL OF !NTIMICROBIAL #HEMOTHERAPY 553-561. 7ALTON * 2 , 1978. The effect of dietary avoparcin on the antibiotic resistance patterns of enteric and pharyngeal bacteria isolated from broiler chickens. :ENTRALBLATT F¼R 6ETERI¤RMEDIZIN 2HEIE " 290-300. $RIESSEN # AND 3TOBBERINGH % , 1996. of resistant faecal bacteria in , farmers and slaughterers. )N PROCEEDINGS OF TH )#! * *ENSEN , " AND 3TOBBERING % % , 1997. An identical VRE isolated from a and a farmer (letter). 6AN DER !UWERA 0 0ENSART . +ORTEN 6 -URRAY " AND ,ECLERCQ 2 , 1996. Influence of oral glycopeptides on the faecal flora of human volunteers: selection of highly glycopeptide-resistant enterococci. *OURNAL OF INFECTIOUS DISEASES 1129- 7EGENER ( # -ADSEN - .IELSEN . AND !ARESTRUP & - , 1997. Isolation of vancomycin resistant %NTEROCOCCUS FAECIUM from food. )NTERNATIONAL *OURNAL OF &OOD -ICROBIOLOGY 57-66. 7HITMAN - # 0ITSAKIS 0 ' $E*ESUS % /SBORNE ! * ,EVINSON - % AND *OHNSON # # , 1996. Gastrointestinal tract colonisation with vancomycin-resistant %NTEROCOCCUS FAECIUM in an animal model. !NTIMICROBIAL !GENTS AND #HEMOTHERAPY 1526-1530. 0 -ORRISON $ AND 3PELLER $ # % , 1995a. perspectives on glycopeptide resistance. #LINICAL -ICROBIOLOGY 2EVIEWS 585-615. *ONES " "ACCUS : ,UDLAM ( AND "ROWN $ , 1995b. vancomycin and high level gentamicin resistance genes on the same plasmid in a clinical isolate of %NTEROCOCCUS FAECALIS. *OURNAL OF !NTIMICROBIAL #HEMOTHERAPY :ULALIAN * ,EE ! ( 'ARCES 4 "( /RLOSKI % * AND %GGERT 2 ' , 1979. study of the excretion and tissue distribution in cattle and chickens fed carbon-14 labeled avoparcin lauryl sulfate. !BSTRACTS OF 0APERS !MERICAN #HEMICAL 3OCIETY : Spiramycin, tylosin and virginiamycin Spiramycin and tylosin belong to the macrolide group of antibiotics, while virginiamycin belongs to the streptogramins. Macrolides and streptogramins are not chemically related but they are often grouped together because they show similar antibacterial and are functionally related in their mode of action. A third class, the lincosamides is also often included for the same reason, leading to the acronym MLS (macrolides, lincosamides and streptogramins). They all inhibit protein synthesis and bind to the 50S subunit of the bacterial ribosome. They are mainly against gram- positive aerobic bacteria, various gram-positive and gram-negative anaerobic bacteria. Lincosamides are not used as feed additives and will therefore only be discussed where appropriate. E.1.1 Macrolides (tylosin and spiramycin) Macrolides are derived from products from 3TREPTOMYCES spp. and are characterised by a macrocyclic lactone ring attached to one or more sugar moieties and can, according to the ring structure, be divided into 14-, 15- and 16 lactone ring macrolides (fig. E.I). Erythromycin, a 14 membered lactone, and several newer derivatives are used in human medicine and are important in the treatment of common infections caused by bacteria such as staphylococci, streptococci, mycoplasmas and campylobacters. Macrolides have been suggested as the primary drugs of choice for a number of clinically significant infections in children (, 1992). Among the 16-membered lactones, spiramycin and josamycin have also been evaluated for the treatment of certain protozoal diseases such as toxoplasmosis (, 1994). In veterinary medicine, the 16-membered lactones tylosin and spiramycin have been widely used, both for growth promotion and for therapy. In the EU, spiramycin is approved for growth promotion in poultry, calves, lambs, kids and swine. Dosages range between 5 and 20 ppm for poultry, 5-80 ppm for calves, lambs and kids, and 5-80 ppm for swine. Tylosin is approved for growth promotion in swine, at concentrations between 5 and 40 ppm. Important clinical applications for those and related substances are swine dysentery (3ERPULINA HYODYSENTERIAE) and mycoplasmosis. The figures in this report is only available in the printed version Tentative sketch of erythromycin, spiramycin and tylosin The figures in this report is only available in the printed version second-choice antibiotics for a range of common infections, including mastitis caused by penicillin-resistant staphylococci. therapeutic purposes, tilmicosin, has lately been introduced into the veterinary field, mainly for use against infections with !CTINOBACILLUS PLEUROPNEUMONIAE in swine, 0ASTEURELLA spp in cattle and mycoplasmosis in various animal species (Prescott and Baggot, 1993). Therapeutic dosages of in-feed tylosin for swine are usually around 100 ppm (Prescott and Baggot, 1993). The different macrolides differ to some extent with respect to their pharmacokinetic properties. Common characteristics of the group are high intracellular concentrations and a wide distribution in tissues (Prescott and Baggot, 1993), properties which together with their activity against important pathogens make them a valuable group for therapeutic purposes in both veterinary and human medicine. E.1.2 Streptogramins (virginiamycin) Streptogramins are natural cyclic peptides including substances such as pristinamycins and virginiamycins (fig E.I). They are produced by a variety of 3TREPTOMYCES spp. Streptogramins consist of two components; A (also called M) and B (also called S), each having bacteriostatic activity and acting synergistically. Streptogramins have been sparingly used in human medicine, although there are geographic variations. Pristinamycin and virginiamycin are the most well known substances, but a new derivative, quinpristin-dalfopristin, has recently been launched (Pechere, 1992; Cormican and , 1996; Nicas ET AL , 1997). The role of these substances as therapeutic tools is expected to increase due to the increasing resistance to more commonly used substances. Quinpristin-dalfopristin has been suggested as a new option for the treatment of infections with glycopeptide- (vancomycin) and aminoglycoside-resistant enterococci (Cormican and , 1996; Nicas ET AL , 1997). In animals, virginiamycin is mainly used as a feed additive for growth promotion. Examples of prophylactic or therapeutic applications are swine dysentery and clostridial infections such as necrotic enteritis in poultry. Virginiamycin is permitted for growth promotion in poultry, calves and swine at concentrations between 5 and 50 ppm for poultry, 5-80 ppm for calves and 5-50 ppm for swine. Therapeutic dosages for swine are around 100-150 ppm and for prophylactic treatment of necrotic enteritis in poultry around 40-80 ppm (Prescott and Baggot, 1993; VET., 1997). There are few data available on the pharmacokinetics of streptogramins. Orally administered virginiamycin is not absorbed from the gut (Prescott and Baggot, 1993). E.2 Mode of action and resistance mechanisms The MLS antibiotics inhibit protein synthesis by binding to the 50 S subunit of the bacterial ribosome. By binding to, or near, the peptidyl transferase centre on the ribosome, macrolides prevent the elongation of the peptide being synthesised. Intrinsic resistance to macrolides, lincosamides and streptogramin B (MLSB) in gram negative bacteria is due to low permeability of the outer membrane (Leclercq and Courvalin, 1991b). The most common mechanism of acquired resistance to MLS antibacterials is alteration of the ribosomal target. Inactivation of the drug and efflux from the bacterial cell have also been described. Concerning streptogramin A, the mechanisms of intrinsic resistance are unclear. Described mechanisms of acquired resistance include enzymatic inactivation and efflux.