Virginiamycin
The two-part streptogramin antibiotic mixed into cattle, pig and poultry feed and added to ethanol fermentations, how it works, and the debate over resistance to its human cousins
Virginiamycin is an antibiotic made by the soil bacterium Streptomyces virginiae. It has two parts: virginiamycin M1, a ring-shaped streptogramin A, and virginiamycin S1, a cyclic depsipeptide of the streptogramin B type. Each alone only slows bacteria; together they bind the bacterial ribosome and stop protein synthesis for good. Farmers have fed it to cattle, pigs and chickens to prevent liver abscesses, acidosis and necrotic enteritis, and ethanol plants add it to control bacteria that steal sugar from the yeast. Because human medicine uses related streptogramins, FDA lists it among medically important antimicrobials: since 2017 its feed uses need veterinary oversight and growth-promotion claims are gone.
No established human dose Details ↓
Recommended Dosing
No established human dose
No human dose exists for virginiamycin. In the US it is approved only for animal feed, Drugs@FDA holds no human application, and every study read here was done in bacteria, cattle, chickens, pigs or horses, or modelled risk to people from farm use.
What is it?
Virginiamycin belongs to the streptogramins, antibiotics that come in two structurally different halves. Virginiamycin M1 is a large lactone ring (streptogramin A); virginiamycin S1 is a cyclic hexadepsipeptide (streptogramin B), the part that makes the drug fit an encyclopedia of peptides. Either half on its own slows bacterial growth reversibly. Together they bind neighbouring sites on the large ribosomal subunit, and the M component leaves a lasting change in the ribosome even after it has come off, which is why the pair kills bacteria where each half alone does not.
In the United States virginiamycin has only ever been an animal drug. It is mixed into feed as a Type A medicated article, sold as Stafac and V-Max. In feedlot cattle it reduces liver abscesses and, by holding back the lactic acid-producing bacteria of the rumen, the acidosis that can follow a switch to grain-heavy diets; a pooled analysis of 26 US studies found the effect on liver abscesses rose with the amount in the diet. In broiler chickens it prevents necrotic enteritis caused by Clostridium perfringens, and in pigs it treats and controls swine dysentery. Horse owners in some countries have used it to try to prevent pasture-associated laminitis.
A second use sits outside animals. Ethanol plants that ferment corn or wheat mash fight contamination by lactic acid bacteria, which compete with the yeast and in one study cost up to 11% of the ethanol. Virginiamycin added to the fermenter suppresses most of them, though some strains tolerate it. A pilot-plant study found that most of the drug breaks down during the process but that biologically active traces can remain in the distillers grains sold as cattle feed; feeding those grains to steers made little difference to resistance in their gut bacteria.
The controversy is about resistance. Human medicine uses related streptogramins: quinupristin-dalfopristin, approved in the US in 1999 for vancomycin-resistant Enterococcus faecium, and oral pristinamycin in Europe. These are different molecules, though virginiamycin M1 is chemically the same as pristinamycin IIA. Chickens and pigs fed virginiamycin carry E. faecium resistant to quinupristin-dalfopristin, resistance genes can pass between enterococci, and a 2003 modelling review concluded that farm use had raised the threat to the human drug. Risk assessments by other authors estimated the human harm to be very small. The European Union banned virginiamycin as a growth promoter in 1999.
In the US the question was settled through FDA's Guidance for Industry #213. FDA lists virginiamycin among the medically important antimicrobial drugs it covers: Stafac and V-Max had their production (growth-promotion) indications removed and moved under veterinary oversight, and most combination products were withdrawn. Drugs@FDA holds no human application for virginiamycin. There is no human dose, and the feed amounts on the labels apply only to the animals named on them.
Mechanism of Action
Virginiamycin's two components bind adjacent sites on the bacterial 50S ribosomal subunit; together they block protein synthesis irreversibly, where either alone only slows it.
Two parts, one target
The M component (streptogramin A) increases the ribosome's grip on the S component (streptogramin B) and leaves the ribosome altered after it leaves.
Protein synthesis blocked
The bound pair stops the peptidyl transferase centre from accepting new amino acids, so bacteria cannot make proteins.
Rumen and gut bacteria
It acts mainly on gram-positive bacteria, including the lactic acid producers behind rumen acidosis and Clostridium perfringens in chickens.
Resistance
Enterococci resist it through genes such as satA and vatD that can transfer between strains, and this cross-resists the human streptogramins.
Published Research
These studies were read from their PubMed abstracts on October 29, 2026. They cover how virginiamycin's two components act on the bacterial ribosome, its use in cattle, chickens, pigs and horses, its fate in fuel-ethanol fermentation, studies of resistance in farm bacteria, and risk assessments of what farm use means for human streptogramins. None gave virginiamycin to people. Papers on the human drugs quinupristin-dalfopristin and pristinamycin are listed under References.
How the two components work together
In bacterial cell-free systems both virginiamycin-type components bind the 50S ribosomal subunit; the A (M) component raises the B (S) component's binding about tenfold and causes a lasting change that blocks the peptidyl transferase acceptor site. Macrolides can displace the B component, but not when the A component is present.
Lasting damage from a component that comes off
Virginiamycin M inhibited protein synthesis reversibly on its own, but together with virginiamycin S killed bacteria. Ribosomes exposed to M and then freed of it stayed unable to make protein and bound S as tightly as ribosomes exposed to both, suggesting M acts catalytically rather than one-to-one.
Virginiamycin S binds through a magnesium bridge
Fluorescence studies indicate that virginiamycin S, a cyclic hexadepsipeptide, holds onto the ribosome partly through a magnesium-ion salt bridge at its 3-hydroxypicolinyl group, a residue essential for activity.
One component, many names, changing shape
Virginiamycin M1, also known as pristinamycin IIA, ostreogrycin A and streptogramin A, adopts different shapes in different solvents by NMR, and differs again when bound to the ribosome or to a deactivating enzyme.
Made by Streptomyces virginiae, and bred for more
Virginiamycin is produced by the bacterium Streptomyces virginiae. After mutagenesis and five rounds of genome shuffling, with streptomycin resistance as selection pressure, a stable strain made about 251 mg of virginiamycin per litre of culture, 11.6 times the wild-type strain.
Holds back acid-producing rumen bacteria
In steers stepped up to an all-concentrate diet, virginiamycin lowered Lactobacillus and Streptococcus bovis counts and blocked the rise in Fusobacterium necrophorum. During induced acidosis it kept rumen pH higher and lactate lower than in untreated steers.
Rumen effects rise with the amount fed
In nine cannulated steers on a grain diet, increasing virginiamycin raised rumen pH and the acetate-to-propionate ratio, lowered lactate, increased fibre fermentation and estimated microbial protein flow, in a dose-dependent pattern.
Changes the rumen microbiota, inconsistently
In 76 feedlot cattle in two batches, virginiamycin changed rumen bacterial diversity and composition in one batch but not the other, so its effect differed between seasons.
Liver abscesses and growth in feedlot cattle
Across seven dose-response studies, virginiamycin in finishing diets improved daily gain or feed conversion; pooled analysis showed fewer and less severe liver abscesses at the two higher inclusion levels, with gains of about 3% in growth and 4% in feed conversion.
Pooled analysis of 26 US feedlot studies
Across 26 studies and more than 7,000 cattle, 22.5% of treated animals had liver abscesses against 31.7% of controls; the incidence fell linearly with dietary virginiamycin, and the analysis put its growth effect at about 2.3 times monensin's for the same amount.
Prevents necrotic enteritis deaths in chickens
Broilers infected with Clostridium perfringens and fed virginiamycin at any of five levels had lower mortality and lower intestinal lesion scores than infected birds on unmedicated feed.
No residues in pig tissues
Pigs fed virginiamycin as a growth promoter had no detectable residues in kidney, liver or muscle, even when slaughtered with no withdrawal time.
Controlling bacteria in alcohol fermentation
In wheat mash fermented by yeast, a low level of virginiamycin suppressed most of seven lactobacillus strains and prevented ethanol losses of up to 11%, but Lactobacillus plantarum tolerated it, and some strains grew after a lag when no yeast was present.
What is left in distillers grains
In 15,000-litre pilot fuel-ethanol runs, virginiamycin M fell about 97% from the fermenter to the dried distillers grains, but biologically active antibiotic was still detected in the grains from both treated runs.
Distillers grains with residues fed to cattle
Steers fed distillers grains from fermentations dosed with virginiamycin for seven weeks showed no treatment effect on antimicrobial susceptibility in E. coli or Enterococcus, and only minor, inconsistent differences in one resistance gene.
Resistant enterococci appear and fade in chickens
Broilers fed virginiamycin continuously carried E. faecium resistant to quinupristin-dalfopristin within one to five weeks; after the drug was removed, no resistant isolates were found five weeks later. The resistance was not explained by known genes.
Pigs and chickens fed it for growth
In a prospective controlled study, a few E. faecium isolates from pigs and chickens fed virginiamycin were resistant to quinupristin-dalfopristin, none to vancomycin, and the treated animals did not gain more weight than untreated ones.
A commercial broiler farm
On a commercial broiler farm, feeding virginiamycin or bacitracin did not select for specific resistance in Enterococcus isolates, but virginiamycin use was associated with the resistance gene vatD in litter DNA.
A transferable resistance gene in farm enterococci
The streptogramin A resistance gene satA was found in a quarter of virginiamycin-resistant E. faecium from pigs and broilers, and streptogramin resistance genes passed between E. faecium strains in mating experiments.
Horses given it to prevent laminitis
Streptogramin-resistant E. faecium were common in horses given virginiamycin, in horses grazing with them and in unexposed horses alike (about 70% of each group), so use against laminitis did not raise resistance, though horses carry the genes.
Modelling the threat to a human streptogramin
Reviewing the epidemiology of E. faecium and modelling the emergence of streptogramin resistance, the authors conclude that long-term virginiamycin use for growth promotion, interacting with human use of quinupristin-dalfopristin, has made high-level resistance genes more common and mobile and threatens the human drug.
Risk model: US and Australian chickens
Working backward from human cases of vancomycin-resistant E. faecium, this risk simulation estimated that banning virginiamycin in chickens would prevent fewer than one statistical death over five years in either the US or Australia.
Risk-benefit estimate of withdrawal
A rapid risk-rating model estimated that withdrawing virginiamycin from food animals could cause far more human campylobacter illness through extra pathogens in meat than it would prevent in resistant enterococcal infections, while noting the conclusion is not deterministic.
Risk model: food animals in China
Under deliberately risk-maximising assumptions, this model estimated the human health risk in China from virginiamycin use in food animals at somewhere between zero and one shortened life every few decades or longer, with zero the most likely value.
No Established Human Dose
No human dose exists for virginiamycin. In the US it is approved only for animal feed, Drugs@FDA holds no human application, and every study read here was done in bacteria, cattle, chickens, pigs or horses, or modelled risk to people from farm use. The feed levels on the veterinary labels and in these trials are amounts per ton of feed for named animals, are not shown as doses, and none applies to a person.
What this rests on: PMID 29846632, PMID 16151077, PMID 15028017.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
No product is approved for people. The approved veterinary product, as its US veterinary label describes it:
- Stafac 500 (virginiamycin powder) (veterinary): Packages the label lists: 45.3 kg drum, 25 kg box, 600 kg bag and 800 kg bag.
Source: Stafac 500 (virginiamycin powder) veterinary label, package list (DailyMed version 11, effective August 19, 2026).
Mixing a vial: a worked example
Unknown: no human dose of Virginiamycin has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
No product of Virginiamycin is approved for people. The US veterinary label of the approved animal product says how it is stored:
Stafac 500 (virginiamycin powder) (veterinary): “Store At Or Below 25 °C (77 °F), Excursions Permitted Up to 40 °C (104 °F)” “Close Container After Use”
These describe the veterinary product in its own container, not a vial sold for people. The mixing guide sets out the general rules for a mixed vial, with their sources.
Source: Stafac 500 (virginiamycin powder) veterinary label, storage section (DailyMed version 11, effective August 19, 2026).
How it is taken
Unknown: with no established human dose, there is no established way of taking Virginiamycin. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long Virginiamycin lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: Selection of E. faecium resistant to the human drug quinupristin-dalfopristin in chickens and pigs fed it (PMIDs 16151077, 14607416); Transferable streptogramin resistance genes in enterococci from farm animals (PMID 9812375); Biologically active residues in distillers grains from treated ethanol fermentations (PMID 27038946); Inconsistent effects on the rumen microbiota of feedlot cattle (PMID 39355681). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Virginiamycin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Reported in animals and in studies of resistance; no human safety data come from these sources”).
Interactions
Unknown: a PubMed search for human interaction studies of Virginiamycin (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Virginiamycin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Virginiamycin's expected mass, 1,349.5 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Veterinary Only (Approved only for animals). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Reported in animals and in studies of resistance; no human safety data come from these sources.
Contraindications & Cautions
For people, the main point is that virginiamycin is not a human medicine in the US.
Legal Status
Virginiamycin is a veterinary feed antibiotic in the US, now under veterinary oversight; it has no human approval there.
Frequently Asked Questions
?What is virginiamycin?
A streptogramin antibiotic from Streptomyces virginiae made of two components, virginiamycin M1 and the cyclic depsipeptide virginiamycin S1, which together block the bacterial ribosome.
?What is it used for?
In the US, as a feed additive for cattle, pigs and poultry: preventing liver abscesses and acidosis in feedlot cattle, necrotic enteritis in broilers and swine dysentery in pigs. Ethanol plants also add it to control lactic acid bacteria in fermentations.
?Is virginiamycin used in people?
Not in the US: Drugs@FDA holds no human application, and the feed products are labelled not for human use. Related human streptogramins, quinupristin-dalfopristin and pristinamycin, are different products.
?Is virginiamycin the same as pristinamycin?
Not as a product. Virginiamycin M1 is the same molecule as pristinamycin IIA, but the B components differ and the products are separate drugs.
?Why is its farm use controversial?
Feeding it selects enterococci resistant to quinupristin-dalfopristin, a human drug for vancomycin-resistant infections, and resistance genes can transfer. Risk models disagree on how much this harms people; the EU banned growth-promoter use in 1999 and the US removed growth-promotion claims under GFI #213.
?Does it leave residues in food?
A study in pigs found no residues in kidney, liver or muscle, but active traces can remain in distillers grains from treated ethanol fermentations.
References
- [other] PubChem CID 127053480, Virginiamycin: formula C71H84N10O17, molecular weight 1349.5. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/127053480
- [other] ChEBI CHEBI:46416, virginiamycin S1: defined as a cyclodepsipeptide and one of the two major components of the antibacterial drug virginiamycin. Read October 28, 2026. https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:46416
- [fda-pi] Stafac 500 (virginiamycin) Type A medicated article, US FDA-approved veterinary label (active ingredient, caution and directions for use; DailyMed set 6e136d64, version 11, effective August 19, 2026; read October 28, 2026).
- [other] US FDA Center for Veterinary Medicine, Approved Animal Drug Products (Green Book), Section 2 active-ingredient list downloaded from Animal Drugs @ FDA, read October 28, 2026: NADA 091-467, Stafac 500, 10, 20 and 50; NADA 140-998, V-Max and V-Max 50; active ingredient virginiamycin. https://animaldrugsatfda.fda.gov/adafda/views/#/search
- [fda] US FDA, List of Medically Important Antimicrobial Drugs Affected by GFI #213 (content current as of May 22, 2024; read October 29, 2026): virginiamycin NADA 091-467 and NADA 140-998, production indications removed and changed to veterinary oversight; most virginiamycin combination NADAs withdrawn. https://www.fda.gov/animal-veterinary/judicious-use-antimicrobials/list-affected-applications
- [other] US FDA, Drugs@FDA (openFDA): no application for virginiamycin. Read October 28, 2026.
- [pubmed] Cocito C, et al. "Molecular mechanism of action of virginiamycin-like antibiotics (synergimycins) on protein synthesis in bacterial cell-free systems." J Antimicrob Chemother, 1985;16 Suppl A:35-52. PMID: 3932310.
- [pubmed] Parfait R, et al. "Lasting damage to bacterial ribosomes by reversibly bound virginiamycin M." Proc Natl Acad Sci U S A, 1980;77(9):5492-6. PMID: 6776538.
- [pubmed] Di Giambattista M, et al. "Interaction between virginiamycin S and ribosomes is partly provided by a salt bridge with a Mg2+ ion." Biochemistry, 1991;30(29):7277-82. PMID: 1906740.
- [pubmed] Dang J, et al. "Solvent affects the conformation of virginiamycin M1 (pristinamycin IIA, streptogramin A)." Org Biomol Chem, 2004;2(20):2919-24. PMID: 15480455.
- [pubmed] Tong QQ, et al. "Genome shuffling and ribosome engineering of Streptomyces virginiae for improved virginiamycin production." Bioprocess Biosyst Eng, 2018;41(5):729-738. PMID: 29457193.
- [pubmed] Coe ML, et al. "Effect of virginiamycin on ruminal fermentation in cattle during adaptation to a high concentrate diet and during an induced acidosis." J Anim Sci, 1999;77(8):2259-68. PMID: 10462007.
- [pubmed] Dias Batista LF, et al. "The influence of virginiamycin on digestion and ruminal parameters under feedlot conditions." Transl Anim Sci, 2024;8:txae019. PMID: 38406320.
- [pubmed] Santos BP, et al. "Impact of virginiamycin on the ruminal microbiota of feedlot cattle." Can J Vet Res, 2024;88(4):114-122. PMID: 39355681.
- [pubmed] Rogers JA, et al. "Effects of dietary virginiamycin on performance and liver abscess incidence in feedlot cattle." J Anim Sci, 1995;73(1):9-20. PMID: 7601759.
- [pubmed] Tedeschi LO, et al. "An assessment of the effectiveness of virginiamycin on liver abscess incidence and growth performance in feedlot cattle: a comprehensive statistical analysis." J Anim Sci, 2018;96(6):2474-2489. PMID: 29846632.
- [pubmed] George BA, et al. "Virginiamycin effects on controlling necrotic enteritis infection in chickens." Poult Sci, 1982;61(3):447-50. PMID: 6806795.
- [pubmed] Lauridsen MG, et al. "Determination and depletion of residues of carbadox, tylosin, and virginiamycin in kidney, liver, and muscle of pigs in feeding experiments." J Assoc Off Anal Chem, 1988;71(5):921-5. PMID: 3148611.
- [pubmed] Hynes SH, et al. "Use of virginiamycin to control the growth of lactic acid bacteria during alcohol fermentation." J Ind Microbiol Biotechnol, 1997;18(4):284-91. PMID: 9172435.
- [pubmed] Bischoff KM, et al. "Fate of virginiamycin through the fuel ethanol production process." World J Microbiol Biotechnol, 2016;32(5):76. PMID: 27038946.
- [pubmed] Walter AL, et al. "Assessment of antibiotic resistance from long-term bacterial exposure to antibiotics commonly used in fuel ethanol production." World J Microbiol Biotechnol, 2019;35(4):66. PMID: 30941513.
- [pubmed] Edrington TS, et al. "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." J Anim Sci, 2014;92(3):1144-9. PMID: 24492576.
- [pubmed] McDermott PF, et al. "Changes in antimicrobial susceptibility of native Enterococcus faecium in chickens fed virginiamycin." Appl Environ Microbiol, 2005;71(9):4986-91. PMID: 16151077.
- [pubmed] Donabedian S, et al. "Antimicrobial resistance in swine and chickens fed virginiamycin for growth promotion." J Microbiol Methods, 2003;55(3):739-43. PMID: 14607416.
- [pubmed] Thibodeau A, et al. "Antibiotic resistance in Escherichia coll and Enterococcus spp. isolates from commercial broiler chickens receiving growth-promoting doses of bacitracin or virginiamycin." Can J Vet Res, 2008;72(2):129-36. PMID: 18505201.
- [pubmed] Hammerum AM, et al. "Detection of the satA gene and transferability of virginiamycin resistance in Enterococcus faecium from food-animals." FEMS Microbiol Lett, 1998;168(1):145-51. PMID: 9812375.
- [pubmed] Menzies-Gow NJ, et al. "Antibiotic resistance in faecal bacteria isolated from horses receiving virginiamycin for the prevention of pasture-associated laminitis." Vet Microbiol, 2011;152(3-4):424-8. PMID: 21676560.
- [review] Smith DL, et al. "Assessing risks for a pre-emergent pathogen: virginiamycin use and the emergence of streptogramin resistance in Enterococcus faecium." Lancet Infect Dis, 2003;3(4):241-9. PMID: 12679267.
- [review] Cox LA Jr, et al. "Quantifying human health risks from virginiamycin used in chickens." Risk Anal, 2004;24(1):271-88. PMID: 15028017.
- [review] Cox LA Jr. "Potential human health benefits of antibiotics used in food animals: a case study of virginiamycin." Environ Int, 2005;31(4):549-63. PMID: 15871160.
- [review] Cox LA Jr, et al. "Quantifying Human Health Risks from Virginiamycin Use in Food Animals in China." Risk Anal, 2020;40(6):1244-1257. PMID: 32315459.
- [pubmed] Crooy P, et al. "Virginiamycin: nomenclature." J Antibiot (Tokyo), 1972;25(6):371-2. PMID: 4568014.
- [pubmed] Manfredi R. "A re-emerging class of antimicrobial agents: streptogramins (quinupristin/dalfopristin) in the management of multiresistant gram-positive nosocomial cocci in hospital setting." Mini Rev Med Chem, 2005;5(12):1075-81. PMID: 16375753.
- [pubmed] Cooper EC, et al. "Pristinamycin: old drug, new tricks?." J Antimicrob Chemother, 2014;69(9):2319-25. PMID: 24891428.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Regulatory status comes from the FDA's list of medically important antimicrobial drugs affected by GFI #213 (read October 29, 2026), the Stafac 500 label on DailyMed, the FDA Green Book and Drugs@FDA (read October 28, 2026). A PubMed search for virginiamycin in titles and abstracts returned 654 records; ClinicalTrials.gov, Drugs@FDA and the EMA list returned none (October 28, 2026). Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.