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Current Opinion in Investigational... Oct 2000Rhône-Poulenc Rorer (RPR) developed Synercid (RP-59500), an injectable synergistic combination of quinupristin and dalfopristin as a treatment for a variety of...
Rhône-Poulenc Rorer (RPR) developed Synercid (RP-59500), an injectable synergistic combination of quinupristin and dalfopristin as a treatment for a variety of infections caused by Gram-positive anaerobic bacteria. The treatment was approved in the UK in July 1999, for use in patients with nosocomial pneumonia, skin and soft tissue infections and clinically significant infections due to Enterococcus faecium when there is no other active antibacterial agent [337556,335257]. It was launched in the UK and the US in September 1999 [342899]. In December 1999, Synercid successfully completed the Mutual Recognition Procedure in the EU under Aventis Pharma for use in patients with these infections [351525]. In September 2000, Merrill Lynch predicted first-year sales in 1999 of Euro 15 million, rising to Euro 171 million in 2004 [384874]. In January 1999, BT Alex Brown predicted sales of US $88 million in 1999 rising to US $450 million in 2002 [318220]. In April 1999, ABN Amro predicted annual sales of DM 30 million in 1999, rising to DM 150 million in 2002 [328676].
Topics: Animals; Bacterial Infections; Clinical Trials as Topic; Contraindications; Drug Therapy, Combination; Humans; Structure-Activity Relationship; Virginiamycin
PubMed: 11249570
DOI: No ID Found -
Biochimica Et Biophysica Acta Apr 1979Although the main characteristics of the parent virginiamycin S conformation i.e. a bend of type VI (Lewis, P.N., Momamy, F.A. and Scheraga, H.A. (1973) Biochim....
Although the main characteristics of the parent virginiamycin S conformation i.e. a bend of type VI (Lewis, P.N., Momamy, F.A. and Scheraga, H.A. (1973) Biochim. Biophys. Acta 303, 211--229) formed by the Pro-N-MePhe-X-PhGly sequence is still present in patricin A, the substitution of X = pipecolic acid by proline in the latter results in a destabilization of the tertiary structure of the depsipeptide, since two isomeric states of a peptidic bond appear in C2HC13 solution. Addition of +/- 30% (v:v) (C2H3)2SO totally shifts this equilibrium in favor of the major parent isomer. These results completely fit with what is known up to now on the occurrence and structure of turns (Chou and Fasman (1977) J. Mol. Biol. 115,135--175).
Topics: Models, Chemical; Molecular Conformation; Proline; Solutions; Spectrum Analysis; Virginiamycin
PubMed: 110355
DOI: 10.1016/0005-2795(79)90037-0 -
Drugs 1996Streptogramin antibiotics represent a unique class of antibacterials in that each member of the class consists of at least 2 structurally unrelated molecules: group A... (Review)
Review
Streptogramin antibiotics represent a unique class of antibacterials in that each member of the class consists of at least 2 structurally unrelated molecules: group A streptogramins (macrolactones) and group B streptogramins (cyclic hexadepsipeptides). Both group A and group B streptogramins inhibit protein synthesis at the ribosomal level, and they act synergistically against many isolates, their combination generating bactericidal activities and reducing the possibility of emergence of resistant strains. The mechanisms of acquired resistance to group B streptogramins are similar to those induced by erythromycin, but group A streptogramins remain unaffected by target modifications and active efflux. The pharmacokinetic parameters of group A and group B streptogramins in blood are quite similar. In addition, both the A and B groups penetrate and accumulate in macrophages and in the bacterial vegetations of experimental endocarditis. There are important structural and biological differences between the streptogramins and the macrolides. The main differentiating features are the rapid anti-bacterial killing of streptogramins and the rarity of cross-resistance between the 2 groups of antibiotics.
Topics: Anti-Bacterial Agents; Drug Synergism; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Virginiamycin
PubMed: 8724812
DOI: 10.2165/00003495-199600511-00005 -
The Canadian Veterinary Journal = La... Mar 1974
Topics: Animals; Dysentery; Swine; Virginiamycin
PubMed: 4598738
DOI: No ID Found -
American Journal of Veterinary Research Oct 1977Virginiamycin, fed at a concentration of 110 mg/kg of feed for 2 weeks followed by concentrations of either 27.5 or 55 mg/kg for 3 weeks, was effective in treatment and...
Virginiamycin, fed at a concentration of 110 mg/kg of feed for 2 weeks followed by concentrations of either 27.5 or 55 mg/kg for 3 weeks, was effective in treatment and control of experimentally induced swine dysentery. However, diarrhea recurred 4 days after withdrawal of medicated feed. Subsequently, the frequency of diarrhea decreased in 3 of 4 groups retreated with virginiamycin (110 mg/kg of feed) for 5 days. Feeding of virginiamycin (110 mg/kg) for 1 week after onset of diarrhea was of little value because of the development of a more severe (augmented) form of the disease after withdrawal of medicated feed. Feeding of virginiamycin (55 mg/kg) at the time of exposure and continuing for 3 weeks (followed by intermittent retreatments of 55 mg/kg) aided in treatment and control of swine dysentery. With this regimen, a few swine developed diarrhea during initial medication, but all developed diarrhea after withdrawal fo medicated feed. Frequency of diarrhea was less after each retreatment. This was attributed to the development of immunity from the recurring diarrhea.
Topics: Administration, Oral; Animal Feed; Animals; Dysentery; Swine; Swine Diseases; Virginiamycin
PubMed: 412441
DOI: No ID Found -
Contact Dermatitis Jun 1978A warehouseman aged 31 working in a pharmaceutical factory got an occupational contact dermatitis to virginiamycin (factor M), an antibiotic used as a food additive for...
A warehouseman aged 31 working in a pharmaceutical factory got an occupational contact dermatitis to virginiamycin (factor M), an antibiotic used as a food additive for pigs and poultry. A review is made of contact dermatitis to virginiamycin and to pristinamycin.
Topics: Adult; Animal Feed; Dermatitis, Occupational; Humans; Male; Patch Tests; Virginiamycin
PubMed: 149638
DOI: 10.1111/j.1600-0536.1978.tb03758.x -
The Analyst Aug 2001A method for the detection of virginiamycin M1 as a marker compound of virginiamycin at sub-additive level in pig, calf, piglet, sow, poultry, cattle and laying hen...
A method for the detection of virginiamycin M1 as a marker compound of virginiamycin at sub-additive level in pig, calf, piglet, sow, poultry, cattle and laying hen feeds was developed and validated. Both UV detection at 230 nm and MS detection were applied. Virginiamycin M1 was extracted from animal feeds with ethyl acetate after wetting of the feed with water followed by clean-up on Sep-Pak silica gel and OASIS HLB cartridges. Analysis of extracts was carried out on an Inertsil ODS-2 column with acetonitrile-water-formic acid as the mobile phase and UV detection at 230 nm. The limit of quantification (LOQ) of the method was 2.7 mg kg(-1). The proposed method was validated at a target species dependent minimum required performance limit (MRPL), at 2MRPL and at 5MRPL levels in pig, calf, piglet, sow, poultry, cattle and laying hen feeds. Recoveries at target species dependent MRPL levels ranged from 38 to 67%, within-day repeatabilities from 7 to 19% and within-laboratory reproducibilities from 13 to 27%. The proposed UV method is primarily suitable for screening purposes at subadditive levels, but semi-quantitative data can also be produced. Three MS detection modes (ion-source CID, full MS and MS2) were tested as an alternative and/or extension to UV detection. The selectivity and sensitivity of both LC-MS2 and LC-MS were much better than those of UV detection at 230 nm.
Topics: Animal Feed; Anti-Bacterial Agents; Drug Residues; Food Contamination; Virginiamycin
PubMed: 11534601
DOI: 10.1039/b102931m -
Journal of Animal Science Mar 2014Dried distiller's grains (DG) produced from ethanol fermentations dosed with 0 (control), 2, or 20 mg/kg virginiamycin-based product or spiked with virginiamycin (VM)... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of feeding distiller's grains, containing virginiamycin, on antimicrobial susceptibilities in fecal isolates of Enterococcus and Escherichia coli and prevalence of resistance genes in cattle.
Dried distiller's grains (DG) produced from ethanol fermentations dosed with 0 (control), 2, or 20 mg/kg virginiamycin-based product or spiked with virginiamycin (VM) postfermentation were fed to cattle and effects on antimicrobial susceptibility, and prevalence of antimicrobial resistance genes in commensal bacteria was examined. Biological activity assays of DG (from each fermentation) indicated a concentration of 0, 0.7, and 8.9 mg/kg VM, respectively. Twenty-four crossbred beef steers were fed 1 of 4 diets (containing 8% of each of the different batches of DG) and a fourth using 8% of the control DG (0 mg/kg VM) + 0.025 g/kg V-Max50 (positive control) for 7 wk. Fecal samples were collected weekly throughout the experimental period and cultured for Escherichia coli and Enterococcus, and isolates were examined for antimicrobial susceptibility, antimicrobial resistance genes (vatE, ermB, and msrC in Enterococcus), and integrons (E. coli). No treatment differences (P > 0.05) were observed in antimicrobial susceptibility of the E. coli isolates. Enterococcus isolates were resistant to more antimicrobials; however, this was influenced by the species of Enterococcus and not treatment (P > 0.10). The prevalence of ermB was greater (P < 0.05) in the control isolates after 4 and 6 wk while at wk 7, prevalence was greater (P < 0.01) in the 0.7 and 8.9 mg/kg VM treatments. Taken together, the minor treatment differences observed for the presence of ermB coupled with the lack of effect on antimicrobial susceptibility patterns suggest that feeding DG containing VM residues should have minimal if any impact on prevalence of antimicrobial resistance.
Topics: Animal Feed; Animals; Anti-Bacterial Agents; Cattle; Diet; Drug Resistance, Bacterial; Edible Grain; Enterococcus; Escherichia coli; Feces; Male; Virginiamycin
PubMed: 24492576
DOI: 10.2527/jas.2013-6954 -
Journal of Bacteriology Sep 2002The visA gene of Streptomyces virginiae has been thought to be a part of the virginiamycin S (VS) biosynthetic gene cluster based on its location in the middle of genes...
The visA gene of Streptomyces virginiae has been thought to be a part of the virginiamycin S (VS) biosynthetic gene cluster based on its location in the middle of genes that encode enzymes highly similar to those participating in the biosynthesis of streptogramin-type antibiotics. Heterologous expression of the visA gene was achieved in Escherichia coli by an N-terminal fusion with thioredoxin (TrxA), and the intact recombinant VisA protein (rVisA) was purified after cleavage with enterokinase to remove the TrxA moiety. The purified rVisA showed clear L-lysine 2-aminotransferase activity with an optimum pH of around 8.0 and an optimum temperature at 35 degrees C, with 2-oxohexanoate as the best amino acceptor, indicating that VisA converts L-lysine into Delta(1)-piperidine 2-carboxylic acid. A visA deletion mutant of S. virginiae was created by homologous recombination, and the in vivo function of the visA gene was studied by phenotypic comparison between the wild type and the visA deletion mutant. No differences in growth in liquid media or in morphological behavior on solid media were observed, indicating that visA is not involved in primary metabolism or morphological differentiation. However, the visA mutant failed to produce VS while maintaining the production of virginiamycin M(1) at a level comparable to that of the parental wild-type strain, demonstrating that visA is essential to VS biosynthesis. These results, together with the observed recovery of the defect in VS production by the external addition of 3-hydroxypicolinic acid (3-HPA), a starter molecule in VS biosynthesis, suggest that VisA is the first enzyme of the VS biosynthetic pathway and that it supplies 3-HPA from L-lysine.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Escherichia coli; Recombinant Proteins; Streptogramin Group B; Streptomyces; Transaminases; Transcription, Genetic; Virginiamycin
PubMed: 12169606
DOI: 10.1128/JB.184.17.4811-4818.2002 -
Poultry Science Jan 1983The purpose of this study was to determine the effect of virginiamycin on the course of an experimentally induced infection of Salmonella typhimurium in broilers....
The purpose of this study was to determine the effect of virginiamycin on the course of an experimentally induced infection of Salmonella typhimurium in broilers. Several parameters were evaluated, including effects on the persistence and duration of shedding of the infecting Salmonella organism and its antibiotic resistance patterns. Virginiamycin was administered to the experimentally infected group for 8 weeks in feed at concentrations of 25 g/ton. This was compared to an infected control group not receiving the antibiotic. No effects were exhibited by virginiamycin on Salmonella typhimurium shedding and antibiotic resistance patterns.
Topics: Animals; Anti-Bacterial Agents; Chickens; Drug Resistance, Microbial; Food Additives; Poultry Diseases; Salmonella Infections, Animal; Salmonella typhimurium; Virginiamycin
PubMed: 6402770
DOI: 10.3382/ps.0620030