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Drugs 1996The prevalence of penicillin-resistant pneumococci is increasing worldwide. Methods for susceptibility testing, as well as in vitro susceptibility of... (Review)
Review
The prevalence of penicillin-resistant pneumococci is increasing worldwide. Methods for susceptibility testing, as well as in vitro susceptibility of penicillin-susceptible and -resistant strains to new and existing agents (including oral and parenteral streptogramins), are described. For all specimens except CSF, oxacillin screening followed by determination of penicillin minimum inhibitory concentrations (MICs) is satisfactory. For CSF, simultaneous testing of penicillin and cefotaxime or ceftriaxone by E-test is necessary. Of all available oral beta-lactams, amoxicillin yields the lowest MICs against penicillin-susceptible and -resistant pneumococci, and is the drug of choice for the treatment of otitis media. Cefotaxime and ceftriaxone yield MICs that are low enough to permit therapy of meningitic and nonmeningitic infections (the former in combination with vancomycin). The higher the strain's benzylpenicillin (penicillin G) MIC, the more likely it is that simultaneous resistance to nonrelated compounds such as tetracyclines, macrolides, and cotrimoxazole (trimethoprim/ sulfamethoxazole) will occur. None of the available quinolones should be used for therapy of pneumococcal infections. Of new and experimental drugs, some of the new quinolones, trovafloxacin, and oral and parenteral streptogramins are promising agents. Imipenem is epileptogenic, but meropenem has potential in the therapy of meningitis. Problematical infections caused by penicillin-resistant pneumococci include meningitis and otitis media. The optimal therapy of the latter two diseases has not yet been clearly delineated.
Topics: Administration, Oral; Drug Resistance, Microbial; Lactams; Microbial Sensitivity Tests; Quinolones; Streptococcus pneumoniae; Virginiamycin
PubMed: 8724810
DOI: 10.2165/00003495-199600511-00003 -
The Veterinary Record Sep 1992
Comparative Study
Topics: Animal Feed; Animals; Brachyspira hyodysenteriae; Drug Resistance, Microbial; Dysentery; Rectum; Specific Pathogen-Free Organisms; Spirochaetales Infections; Swine; Swine Diseases; Virginiamycin
PubMed: 1441115
DOI: 10.1136/vr.131.11.239 -
Scientific Reports Sep 2017Distillers grains are co-products of the corn ethanol industry widely used in animal feed. We examined the effects of erythromycin, penicillin, and virginiamycin at low...
Distillers grains are co-products of the corn ethanol industry widely used in animal feed. We examined the effects of erythromycin, penicillin, and virginiamycin at low concentrations reflective of those detected in distillers grains on bacterial resistance selection. At 0.1 µg/ml erythromycin, macrolide-resistant mutants were induced in one Campylobacter coli and one Enterococcus faecium strain, while these strains plus three additional C. coli, one additional E. faecium, and one C. jejuni also developed resistance when exposed to 0.25 µg/ml erythromycin. At 0.5 µg/ml erythromycin, a total of eight strains (four Campylobacter and four Enterococcus) obtained macrolide-resistant mutants, including two strains from each genus that were not selected at lower erythromycin concentrations. For penicillin, three of five E. faecium strains but none of five Enterococcus faecalis strains consistently developed resistance at all three selection concentrations. Virginiamycin at two M:S ratios did not induce resistance development in four out of five E. faecium strains; however, increased resistance was observed in the fifth one under 0.25 and 0.5 µg/ml virginiamycin selections. Although not yet tested in vivo, these findings suggest a potential risk of stimulating bacterial resistance development in the animal gut when distillers grains containing certain antibiotic residues are used in animal feed.
Topics: Anti-Bacterial Agents; Campylobacter; Drug Resistance, Bacterial; Enterococcus; Erythromycin; Mutation Rate; Penicillins; Selection, Genetic; Virginiamycin
PubMed: 28887450
DOI: 10.1038/s41598-017-09593-4 -
Nucleic Acids Research Oct 1994Previous findings suggest the location of the central loop of domain V of 23S rRNA within the peptidyltransferase domain of ribosomes. This enzymatic activity is...
Previous findings suggest the location of the central loop of domain V of 23S rRNA within the peptidyltransferase domain of ribosomes. This enzymatic activity is inhibited by some antibiotics, including type A (virginiamycin M or VM) and type B (virginiamycin S or VS) synergimycins, antibiotics endowed with a synergistic action in vivo. In the present work, the ability of VM and VS to modify the accessibility of 23S rRNA bases within ribosomes to chemical reagents has been explored. VM afforded a protection of rRNA bases A2037, A2042, G2049 and C2050. Moreover, when ribosomes were incubated with the two virginiamycin components, the base A2062, which was protected by VS alone, became accessible to dimethyl sulphate (DMS). Modified reactivity to chemical reagents of different rRNA bases located either in the central loop of domain V or in its proximity furnishes experimental evidence for conformational ribosome alterations induced by VM binding.
Topics: Aldehydes; Base Sequence; Butanones; Diethyl Pyrocarbonate; Drug Synergism; Molecular Sequence Data; Nucleic Acid Conformation; Peptidyl Transferases; Protein Conformation; RNA, Ribosomal, 23S; Ribosomes; Sulfuric Acid Esters; Virginiamycin
PubMed: 7971275
DOI: 10.1093/nar/22.21.4449 -
Veterinarni Medicina May 1995Virginiamycin is an antibiotic active against grampositive bacteria in the alimentary tract, which is also suitable for supplementation of diets of growing and finishing...
Virginiamycin is an antibiotic active against grampositive bacteria in the alimentary tract, which is also suitable for supplementation of diets of growing and finishing ruminants. The aim of this work was to specify the effect of virginiamycin on some parameters of rumen fermentation in vitro with inoculi taken from wethers adapted or non-adapted to the virginiamycin intake. Incubations were performed anaerobically at 39 degrees C in serum bottles closed with Bunsen valves. Virginiamycin was added at 0 or 10 mg/l to the rumen fluid diluted with McDougall buffer. Virginiamycin significantly decreased production and utilization of lactic acid, production of methane and decomposition of casein when rumen fluid was taken from non-adapted wethers. Most of its effects disappeared when rumen fluid was sampled from wethers adapted to the virginiamycin intake (100 mg per head daily for 2 months). Adaptation of wethers to virginiamycin was further confirmed by analyses of the rumen fluid which was used for inoculation of in vitro cultures. Molar percentages of acetate, propionate, butyrate and valerate were the same before and after the adaptation. Therefore it can be concluded that the effects of virginiamycin on rumen parameters are not stable and its addition to ruminant diets cannot be recommended, with exception of the milk nutrition period. In the last experiment the stability of virginiamycin in the rumen fluid of adapted wethers was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adaptation, Physiological; Animals; Cattle; Fermentation; In Vitro Techniques; Rumen; Virginiamycin
PubMed: 7793012
DOI: No ID Found -
Journal of the American Chemical Society Sep 2017Streptogramin antibiotics are used clinically to treat multidrug-resistant bacterial infections, but their poor physicochemical properties and narrow spectra of activity...
Streptogramin antibiotics are used clinically to treat multidrug-resistant bacterial infections, but their poor physicochemical properties and narrow spectra of activity have limited their utility. New methods to chemically modify streptogramins would enable structural optimization to overcome these limitations as well as to combat growing resistance to the class. Here we report a modular, scalable synthesis of group A streptogramin antibiotics that proceeds in 6-8 linear steps from simple chemical building blocks. We have applied our route to the synthesis of four natural products in this class including two that have never before been accessed by fully synthetic routes. We anticipate that this work will lead to the discovery of new streptogramin antibiotics that overcome previous limitations of the class.
Topics: Anti-Bacterial Agents; Biological Products; Molecular Structure; Streptogramin Group A; Virginiamycin
PubMed: 28902996
DOI: 10.1021/jacs.7b08577 -
Poultry Science Aug 1988An experiment was conducted to determine the effect of dietary Virginiamycin on processing yields of broilers fed four levels of energy. Body weights (catch, slaughter)... (Comparative Study)
Comparative Study
An experiment was conducted to determine the effect of dietary Virginiamycin on processing yields of broilers fed four levels of energy. Body weights (catch, slaughter) and carcass weights (dry shell and ready-to-cook) were recorded. Shrink (holding weight loss), water uptake, shell yield, and ready-to-cook yield of the carcasses were calculated. Body weights were higher at higher energy levels and with addition of Virginiamycin to the diets. Weight loss due to shrink declined from 5.39 to 3.89% at higher dietary energy levels, but shrink was not affected by Virginiamycin. Water uptake was significantly higher for carcasses of birds fed the lowest dietary energy level (3.49%) than for carcasses of birds fed the two highest energy levels (2.89 and 3.03%); but differences among water uptake of carcasses of birds fed the three highest energy levels were not significant. Water uptake was unaffected by Virginiamycin. Increasing the dietary energy level resulted in higher ready-to-cook yields, from 61.7% yield at 2,271 kcal ME/kg to 65.4% yield at 2,953 kcal ME/kg. Yield was increased from 63.3 to 64.0% (P less than .01) by dietary Virginiamycin.
Topics: Animals; Body Weight; Chickens; Diet; Energy Metabolism; Virginiamycin
PubMed: 3146059
DOI: 10.3382/ps.0671222 -
Revista de Medicina de La Universidad... 2001
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Journal of Animal Science Oct 2016Two experiments were conducted to examine the influence of protein and virginiamycin (VM) supplementation on feedlot growth performance, digestion, and metabolizable AA... (Randomized Controlled Trial)
Randomized Controlled Trial
Two experiments were conducted to examine the influence of protein and virginiamycin (VM) supplementation on feedlot growth performance, digestion, and metabolizable AA (MAA) supply of calf-fed Holstein steers. Growth performance and dietary energetics were evaluated in 120 Holstein steers (127 ± 9 kg). During the initial 112-d feeding period, a steam-flaked corn-based diet was balanced to meet either 100% (MAB) or 87% (UREA) of MAA requirements. Diets were supplemented with or without 22.5 mg/kg VM in a 2 × 2 factorial arrangement. Subsequently (d 112 to 308), all steers received the UREA diet with or without VM. During the initial 112-d, MAB increased ADG, G:F, and dietary NE ( < 0.01). Thereafter, when all steers received the UREA diet, ADG, G:F, and dietary NE were not different ( > 0.10) across initial supplementation treatments. Overall (d 1 to 308), MAB did not affect ADG ( > 0.10) but enhanced G:F efficiency ( = 0.03) and dietary NE ( = 0.05). During the initial 112-d period and through the remainder of the experiment, VM increased G:F ( < 0.01) and dietary NE ( < 0.01). Four Holstein steers (146 ± 4 kg) with cannulas in the rumen and proximal duodenum were used in a 4 × 4 Latin square design to evaluate initial 112-d treatment effects on digestive function. There were no treatment effects ( > 0.10) on ruminal digestion of OM, NDF, starch, microbial efficiency, or total tract digestion of OM and NDF. The MAB increased indispensable AA flow to the small intestine ( < 0.01) and total tract digestion of N ( < 0.01) and starch ( = 0.04). Observed AA supply to small intestine was in agreement with expected supply ( = 0.96). Virginiamycin decreased ( = 0.04) nonammonia N flow to the small intestine and did not affect ( > 0.10) total tract N digestion. Extrapolating from AA supplies in the metabolism study, MAB satisfied indispensable AA requirements during the initial 112-d period, whereas the UREA diet met 73.5% and 79.2% of methionine and lysine requirements, respectively. During the subsequent periods (d 112 to 308) indispensable AA supplies exceeded theoretical requirements. We conclude that enhancements in energy utilization when diets are balanced to meet MAA requirements of calf-fed Holstein steers during the initial 112-d feedlot period remain appreciable throughout time on feed. Virginiamycin enhanced efficiency of energy utilization throughout the feedlot growing-finishing period.
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Cattle; Diet; Dietary Proteins; Dietary Supplements; Digestion; Male; Nutritional Status; Protein Synthesis Inhibitors; Starch; Virginiamycin; Weight Gain
PubMed: 27898843
DOI: 10.2527/jas.2016-0576 -
Accounts of Chemical Research Apr 2021Continued, rapid development of antimicrobial resistance has become worldwide health crisis and a burden on the global economy. Decisive and comprehensive action is...
Continued, rapid development of antimicrobial resistance has become worldwide health crisis and a burden on the global economy. Decisive and comprehensive action is required to slow down the spread of antibiotic resistance, including increased investment in antibiotic discovery, sustainable policies that provide returns on investment for newly launched antibiotics, and public education to reduce the overusage of antibiotics, especially in livestock and agriculture. Without significant changes in the current antibiotic pipeline, we are in danger of entering a post-antibiotic era.In this Account, we summarize our recent efforts to develop next-generation streptogramin and lankacidin antibiotics that overcome bacterial resistance by means of modular chemical synthesis. First, we describe our highly modular, scalable route to four natural group A streptogramins antibiotics in 6-8 steps from seven simple chemical building blocks. We next describe the application of this route to the synthesis of a novel library of streptogramin antibiotics informed by in vitro and in vivo biological evaluation and high-resolution cryo-electron microscopy. One lead compound showed excellent inhibitory activity in vitro and in vivo against a longstanding streptogramin-resistance mechanism, virginiamycin acetyltransferase. Our results demonstrate that the combination of rational design and modular chemical synthesis can revitalize classes of antibiotics that are limited by naturally arising resistance mechanisms.Second, we recount our modular approaches toward lankacidin antibiotics. Lankacidins are a group of polyketide natural products with activity against several strains of Gram-positive bacteria but have not been deployed as therapeutics due to their chemical instability. We describe a route to several diastereomers of 2,18--lankacidinol B in a linear sequence of ≤8 steps from simple building blocks, resulting in a revision of the C4 stereochemistry. We next detail our modular synthesis of several diastereoisomers of -lankacidinol that resulted in the structural reassignment of this natural product. These structural revisions raise interesting questions about the biosynthetic origin of lankacidins, all of which possessed uniform stereochemistry prior to these findings. Finally, we summarize the ability of several - and -lankacidins to inhibit the growth of bacteria and to inhibit translation in vitro, providing important insights into structure-function relationships for the class.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Gram-Negative Bacteria; Gram-Positive Bacteria; Macrolides; Microbial Sensitivity Tests; Molecular Conformation; Molecular Dynamics Simulation; Ribosomes; Streptogramins; Virginiamycin
PubMed: 33792282
DOI: 10.1021/acs.accounts.0c00894