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Drugs Sep 1996Quinupristin-dalfopristin (RP 59500) is an injectable streptogramin antibiotic. It possesses a wide spectrum of activity against Gram-positive bacteria including... (Review)
Review
Quinupristin-dalfopristin (RP 59500) is an injectable streptogramin antibiotic. It possesses a wide spectrum of activity against Gram-positive bacteria including methicillin-resistant staphylococci, glycopeptide-resistant. Enterococcus faecium and penicillin-resistant pneumococci. Quinupristin-dalfopristin has activity against some anaerobes and selected Gram-negative pathogens. Quinupristin-dalfopristin, by way synergism of between its 2 components, is unaffected by most forms of bacterial resistance. Rare forms of macrolide-lincosamide-streptogramin group B resistance may affect its activity; however, at present the incidence of strains with this type of resistance remains low. Quinupristin-dalfopristin is bactericidal against streptococci and staphylococci but has weak or no bactericidal activity against enterococci. In a compassionate use programme, 67% of 95 evaluable patients with vancomycin-resistant Gram-positive infections or intolerant of vancomycin showed improvement with eradication of infection.
Topics: Animals; Anti-Bacterial Agents; Clinical Trials as Topic; Drug Resistance, Microbial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Virginiamycin
PubMed: 8875130
DOI: 10.2165/00003495-199652030-00006 -
World Journal of Microbiology &... May 2016Antibiotics are frequently used to prevent and treat bacterial contamination of commercial fuel ethanol fermentations, but there is concern that antibiotic residues may...
Antibiotics are frequently used to prevent and treat bacterial contamination of commercial fuel ethanol fermentations, but there is concern that antibiotic residues may persist in the distillers grains coproducts. A study to evaluate the fate of virginiamycin during the ethanol production process was conducted in the pilot plant facilities at the National Corn to Ethanol Research Center, Edwardsville, IL. Three 15,000-liter fermentor runs were performed: one with no antibiotic (F1), one dosed with 2 parts per million (ppm) of a commercial virginiamycin product (F2), and one dosed at 20 ppm of virginiamycin product (F3). Fermentor samples, distillers dried grains with solubles (DDGS), and process intermediates (whole stillage, thin stillage, syrup, and wet cake) were collected from each run and analyzed for virginiamycin M and virginiamycin S using a liquid chromatography-mass spectrometry method. Virginiamycin M was detected in all process intermediates of the F3 run. On a dry-weight basis, virginiamycin M concentrations decreased approximately 97 %, from 41 μg/g in the fermentor to 1.4 μg/g in the DDGS. Using a disc plate bioassay, antibiotic activity was detected in DDGS from both the F2 and F3 runs, with values of 0.69 μg virginiamycin equivalent/g sample and 8.9 μg/g, respectively. No antibiotic activity (<0.6 μg/g) was detected in any of the F1 samples or in the fermentor and process intermediate samples from the F2 run. These results demonstrate that low concentrations of biologically active antibiotic may persist in distillers grains coproducts produced from fermentations treated with virginiamycin.
Topics: Anti-Bacterial Agents; Biofuels; Chromatography, Liquid; Ethanol; Fermentation; Mass Spectrometry; Saccharomyces cerevisiae; Virginiamycin; Zea mays
PubMed: 27038946
DOI: 10.1007/s11274-016-2026-3 -
Journal of Chemical Information and... Oct 2023Due to the emergence of antibiotic resistance, the need to explore novel antibiotics and/or novel strategies to counter antibiotic resistance is of utmost importance. In...
Due to the emergence of antibiotic resistance, the need to explore novel antibiotics and/or novel strategies to counter antibiotic resistance is of utmost importance. In this work, we explored the molecular and mechanistic details of the degradation of a streptogramin B antibiotic by virginiamycin B (Vgb) lyase of using classical molecular dynamics simulations and multiscale quantum mechanics/molecular mechanics methods. Our results were in line with available experimental kinetic information. Although we were able to identify a stepwise mechanism, in the wild-type enzyme, the intermediate is short-lived, showing a small barrier to decay to the product state. The impact of point mutations on the reaction was also assessed, showing not only the importance of active site residues to the reaction catalyzed by Vgb lyase but also of near positive and negative residues surrounding the active site. Using molecular dynamics simulations, we also predicted the most likely protonation state of the 3-hydroxypicolinic moiety of the antibiotic and the impact of mutants on antibiotic binding. All this information will expand our understanding of linearization reactions of cyclic antibiotics, which are crucial for the development of novel strategies that aim to tackle antibiotic resistance.
Topics: Virginiamycin; Molecular Dynamics Simulation; Lyases; Anti-Bacterial Agents; Catalysis
PubMed: 37791530
DOI: 10.1021/acs.jcim.3c00962 -
Chemotherapy 1969
Topics: Animals; Anti-Bacterial Agents; Bacteriological Techniques; Clostridium; Culture Media; Drug Synergism; Enterobacteriaceae; Haemophilus; Leptospira; Malaria; Mice; Microbial Sensitivity Tests; Mycobacterium; Plasmodium; Protozoan Infections; Staphylococcal Infections; Streptococcal Infections; Toxoplasmosis; Trichomonas; Virginiamycin
PubMed: 4902789
DOI: 10.1159/000220640 -
Risk Analysis : An Official Publication... Jun 2020Virginiamycin (VM), a streptogramin antibiotic, has been used to promote healthy growth and treat illnesses in farm animals in the United States and other countries. The...
Virginiamycin (VM), a streptogramin antibiotic, has been used to promote healthy growth and treat illnesses in farm animals in the United States and other countries. The combination streptogramin Quinupristin-Dalfopristin (QD) was approved in the United States in 1999 for treating patients with vancomycin-resistant Enterococcus faecium (VREF) infections. Many chickens and swine test positive for QD-resistant E. faecium, raising concerns that using VM in food animals might select for streptogramin-resistant strains of E. faecium that could compromise QD effectiveness in treating human VREF infections. Such concerns have prompted bans and phase-outs of VM as growth promoters in the United States and Europe. This study quantitatively estimates potential human health risks from QD-resistant VREF infections due to VM use in food animals in China. Plausible conservative (risk-maximizing) quantitative risk estimates are derived for future uses, assuming 100% resistance to linezolid and daptomycin and 100% prescription rate of QD to high-level (VanA) VREF-infected patients. Up to one shortened life every few decades to every few thousand years might occur in China from VM use in animals, although the most likely risk is zero (e.g., if resistance is not transferred from bacteria in food animals to bacteria infecting human patients). Sensitivity and probabilistic uncertainty analyses suggest that this conclusion is robust to several data gaps and uncertainties. Potential future human health risks from VM use in animals in China appear to be small or zero, even if QD is eventually approved for use in human patients.
Topics: Animals; Anti-Bacterial Agents; Chickens; China; Humans; Meat Products; Microbial Sensitivity Tests; Vancomycin-Resistant Enterococci; Virginiamycin
PubMed: 32315459
DOI: 10.1111/risa.13466 -
Drug Metabolism and Disposition: the... 1988The antibiotic virginiamycin (VM) was extensively metabolized in cattle rumen fluid in vitro. The antimicrobial activity of VM decreased rapidly with an initial...
The antibiotic virginiamycin (VM) was extensively metabolized in cattle rumen fluid in vitro. The antimicrobial activity of VM decreased rapidly with an initial half-life of approximately 8 hr. In contrast, in buffer at near neutral pH, VM maintained its full activity for at least 24 hr. Four metabolites were isolated and identified using a combination of spectral techniques including FAB MS-MS, LC-MS, and 500 MHz NMR. The metabolites were all derived from reduction of the major component of virginiamycin, factor M. The minor component, factor S, was not metabolized in cattle rumen fluid. The metabolic pathways involved included C = C and C = O reduction as well as dehydroxylation. All metabolites were found to have less antimicrobial activity than the parent factor M. In addition to the metabolites, two factor M decomposition products were isolated after incubation of VM in buffer alone. These two products resulted from the dehydration of factor M and were shown to interconvert at room temperature.
Topics: Animals; Body Fluids; Cattle; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Fermentation; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Microbial Sensitivity Tests; Rumen; Spectrophotometry, Ultraviolet; Virginiamycin
PubMed: 2907457
DOI: No ID Found -
Scientific Reports Feb 2018Although dietary antibiotic growth promoters have long been used to increase growth performance in commercial food animal production, the biochemical details associated...
Although dietary antibiotic growth promoters have long been used to increase growth performance in commercial food animal production, the biochemical details associated with these effects remain poorly defined. A metabolomics approach was used to characterize and identify the biochemical compounds present in the intestine of broiler chickens fed a standard, unsupplemented diet or a diet supplemented with the antibiotic growth promoters, virginiamycin or bacitracin methylene disalicylate. Compared with unsupplemented controls, the levels of 218 biochemicals were altered (156 increased, 62 decreased) in chickens given the virginiamycin-supplemented diet, while 119 were altered (96 increased, 23 decreased) with the bacitracin-supplemented diet. When compared between antibiotic-supplemented groups, 79 chemicals were altered (43 increased, 36 decreased) in virginiamycin- vs. bacitracin-supplemented chickens. The changes in the levels of intestinal biochemicals provided a distinctive biochemical signature unique to each antibiotic-supplemented group. These biochemical signatures were characterized by increases in the levels of metabolites of amino acids (e.g. 5-hydroxylysine, 2-aminoadipate, 5-hydroxyindoleaceate, 7-hydroxyindole sulfate), fatty acids (e.g. oleate/vaccenate, eicosapentaenoate, 16-hydroxypalmitate, stearate), nucleosides (e.g. inosine, N-methyladenosine), and vitamins (e.g. nicotinamide). These results provide the framework for future studies to identify natural chemical compounds to improve poultry growth performance without the use of in-feed antibiotics.
Topics: Amino Acids; Analysis of Variance; Animal Feed; Animals; Anti-Bacterial Agents; Bacitracin; Chickens; Dietary Supplements; Fatty Acids; Gastrointestinal Microbiome; Intestines; Metabolome; Niacinamide; Nucleosides; Salicylates; Virginiamycin
PubMed: 29483631
DOI: 10.1038/s41598-018-22004-6 -
Pharmacotherapy Dec 2000Synercid (RP 59500), the first injectable streptogramin antibiotic, is composed of two semisynthetic pristinamycin derivatives, quinupristin and dalfopristin.... (Review)
Review
Synercid (RP 59500), the first injectable streptogramin antibiotic, is composed of two semisynthetic pristinamycin derivatives, quinupristin and dalfopristin. Individually, each component has bacteriostatic activity against staphylococci and streptococci, but together, the agents exhibit synergy, leading to bactericidal activity. The combination drug, however, is bacteriostatic against Enterococcus faecium and has poor activity against Enterococcus faecalis. Despite a short half-life, an extended postantibiotic effect allows the agent to be dosed every 8-12 hours. Both drugs are largely hepatically metabolized and excreted in bile. Although not metabolized by cytochrome P450 3A4, quinupristin-dalfopristin can inhibit agents that are metabolized through this pathway. Dosage adjustments may be necessary in patients with hepatic dysfunction. Alterations in renal function have minimal effects on the agent's pharmacokinetics. Adverse events include arthralgia, myalgias, and infusion-related pain. Based on available data, quinupristin-dalfopristin appears to have a role in treating severely ill patients with infections due to multiresistant gram-positive pathogens.
Topics: Animals; Anti-Bacterial Agents; Bacteremia; Clinical Trials as Topic; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Virginiamycin
PubMed: 11130220
DOI: 10.1592/phco.20.19.1469.34858 -
Journal of the American Chemical Society Mar 2016Modular polyketide synthases (PKSs) direct the biosynthesis of clinically valuable secondary metabolites in bacteria. The fidelity of chain growth depends on specific...
Modular polyketide synthases (PKSs) direct the biosynthesis of clinically valuable secondary metabolites in bacteria. The fidelity of chain growth depends on specific recognition between successive subunits in each assembly line: interactions mediated by C- and N-terminal "docking domains" (DDs). We have identified a new family of DDs in trans-acyl transferase PKSs, exemplified by a matched pair from the virginiamycin (Vir) system. In the absence of C-terminal partner (VirA (C)DD) or a downstream catalytic domain, the N-terminal DD (VirFG (N)DD) exhibits multiple characteristics of an intrinsically disordered protein. Fusion of the two docking domains results in a stable fold for VirFG (N)DD and an overall protein-protein complex of unique topology whose structure we support by site-directed mutagenesis. Furthermore, using small-angle X-ray scattering (SAXS), the positions of the flanking acyl carrier protein and ketosynthase domains have been identified, allowing modeling of the complete intersubunit interface.
Topics: Acyltransferases; Magnetic Resonance Spectroscopy; Models, Molecular; Polyketide Synthases; Virginiamycin
PubMed: 26982529
DOI: 10.1021/jacs.5b13372 -
Journal - Association of Official... May 1979Virginiamycin was extracted from the feed by ethanol-pH 2.5 phosphate buffer (1 + 1). The pH during extraction was adjusted (when necessary) to between 4 and 5. Sample...
Virginiamycin was extracted from the feed by ethanol-pH 2.5 phosphate buffer (1 + 1). The pH during extraction was adjusted (when necessary) to between 4 and 5. Sample dilutions and the standard dose response line were prepared to contain ethanol pH 6 phosphate buffer (2 + 8), and the test organism was Sarcina lutea. Three feeds (a poultry ration, a swine finishing ration, and a swine starter ration) showed virginiamycin recovery of 88.8--108.9% when standard solutions were added at concentrations of 4.54--90.8 g/ton. The coefficient of variation (4--20%) was larger for low potency feeds (10 g/ton) compared to the higher feeds (100 g/ton). Similarly, excellent recovery was obtained when the swine starter feed was fortified by a commercial premix. Amprolium, roxarsone, and monensin can be present at 20 times the concentration of virginiamycin with little or no interference in the antibiotic determination. Lasalocid at 10 times the concentration of virginiamycin caused a slightly positive bias (recovery, 107.4%).
Topics: Animal Feed; Animals; Biological Assay; Hydrogen-Ion Concentration; Sarcina; Swine; Virginiamycin
PubMed: 39060
DOI: No ID Found