Ramoplanin
A gut-acting antibiotic from an Actinoplanes bacterium, tested against VRE carriage and C. difficile but never brought to market
Ramoplanin is a ring-shaped peptide antibiotic, carrying sugars and a fatty-acid tail, made by an Actinoplanes soil bacterium. It kills Gram-positive bacteria, including vancomycin-resistant enterococci (VRE) and Clostridioides difficile, by locking up lipid II, a building block of the bacterial cell wall. Taken by mouth it stays in the gut, so it was developed to clear VRE from the bowel and to treat C. difficile diarrhoea. The FDA gave it fast-track status and phase 2 trials were positive, but no phase 3 result was ever published and it has never been approved anywhere.
Used in human trials: 100 mg, Twice daily, Oral (Study: gut VRE carriage, phase 2 (lower dose)) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Ramoplanin was isolated in the 1980s from a strain of Actinoplanes, a soil bacterium, and described as a new glycolipodepsipeptide antibiotic under the code A-16686. Chemical and NMR work showed it is really three closely related molecules sharing one ring of amino acids, closed partly by an ester bond, with two mannose sugars attached; they differ only in the length of a fatty-acid chain. The main component, ramoplanin A2, is the one whose formula is given here.
It attacks the bacterial cell wall at a different point from vancomycin. Early experiments found that bacteria treated with it piled up cell-wall precursors and that it blocked the step after lipid intermediate I is formed, while binding far fewer molecules per cell than vancomycin. Later work showed it binds lipid II, the next intermediate, as a pair of molecules, so the enzymes that stitch lipid II into the wall have nothing to work on; a 2009 crystal structure showed that dimer and how it sits against the membrane. At higher, bactericidal concentrations it also depolarises the bacterial membrane.
In the laboratory it is active against almost every Gram-positive bacterium tested. Minimum inhibitory concentrations were 0.5 mg/l or less for methicillin-resistant Staphylococcus aureus, for European VRE isolates and for C. difficile, including strains less susceptible to vancomycin or resistant to metronidazole, and it killed enterococci that resisted vancomycin and penicillin combinations. It does little against most Gram-negative gut anaerobes such as Bacteroides, which led researchers to expect less disruption of normal bowel flora. Resistance was hard to provoke but could be selected by repeated passage, and that resistant strain also became less sensitive to vancomycin.
Because it is barely absorbed from the gut, development focused on bowel infections. In a phase 2 trial of 68 VRE carriers, 100 or 400 mg twice daily for a week cleared VRE from stool in most patients, but the bacteria returned within two weeks, usually the same strain, and more often in patients given other antibiotics active against anaerobes. In hamster and gut-model studies of C. difficile it resolved disease like vancomycin and left fewer spores behind, and it appears to cling to the spore surface and kill cells as they germinate. A second phase 2 trial found it comparable to vancomycin for C. difficile colitis.
Reviews in 2003 to 2006 describe FDA fast-track status for preventing enterococcal infection and treating C. difficile, and a placebo-controlled trial in neutropenic cancer patients aimed at preventing VRE bloodstream infection, with phase 3 results expected to decide its place. No phase 3 result appears in PubMed, ClinicalTrials.gov lists no trial under its name, and no regulator lists it as approved. A 2024 laboratory study tested it against gonorrhoea.
Mechanism of Action
Ramoplanin locks up lipid II, the carrier-bound building block that Gram-positive bacteria add to their cell wall, so the wall cannot grow; at high concentrations it also disrupts the membrane.
A different site from vancomycin
It acts before transpeptidation and binds far fewer sites per cell than vancomycin, so vancomycin-resistant strains stay susceptible (1990 study).
Membrane depolarisation
At or above bactericidal concentrations it depolarises the membrane of Staphylococcus aureus and visibly damages the cells (2014 study).
Spores
It sticks to the outer coat of C. difficile spores and kills cells as they germinate, keeping spore counts down for weeks in vitro (2015 study).
Published Research
Studies of ramoplanin itself, read from their PubMed abstracts: the phase 2 VRE trial and its follow-up, reviews of its development, animal models of VRE and C. difficile, and laboratory studies of how it works and what it kills. Studies of semisynthetic derivatives are not carded.
Phase 2: VRE cleared, then back
In a double-blind, placebo-controlled phase 2 trial, 68 patients carrying VRE in the gut took 100 mg or 400 mg twice daily or placebo by mouth for 7 days. On day 7, VRE could not be recovered in 17 of 21 and 18 of 20 treated patients against none of 20 on placebo; by day 14 the difference had shrunk and by day 21 it was gone. Adverse events were similar across groups.
Why VRE came back
Genotyping stool isolates from the same phase 2 trial showed that every treated patient who was culture-positive on day 7 relapsed with a related strain. Taking other antibiotics active against anaerobes made a positive culture about nine times more likely, and avoiding them was linked to staying negative through day 21.
Fast-tracked, phase 2 positive
This review reports FDA fast-track status for preventing enterococcal infection and treating C. difficile, MIC90 values of 1.0 µg/ml or less for the Gram-positive organisms examined, a positive phase 2 VRE trial and a second phase 2 trial showing it equivalent to vancomycin for C. difficile colitis, with its place depending on phase 3.
Pharmacology and safety
Reviewing the literature to 2004 and company data, the authors describe bactericidal activity through lipid II, no documented cross-resistance with vancomycin, minimal adverse effects and no known drug interactions, with trials of oral treatment for C. difficile diarrhoea still running.
Preventing VRE infection
Given by mouth and not absorbed, ramoplanin brought VRE in the gut below detection in 80% to 90% of patients while they took it. A randomised, placebo-controlled trial was then under way to see whether it prevented VRE bloodstream infection in neutropenic patients with blood cancers or stem-cell transplants.
VRE in mice: suppressed but recurrent
In mice, 8 days of ramoplanin in drinking water (100 µg/ml) suppressed VRE to undetectable levels but all mice were recolonised; at 500 µg/ml half were. Some VRE persisted in the colon lining, and treatment let Gram-negative bacteria such as Klebsiella overgrow.
C. difficile: fewer spores than with vancomycin
In clindamycin-primed hamsters and a gut model, ramoplanin and vancomycin both resolved disease and cut toxin, but spores were recovered from the caecum of 19 of 23 vancomycin-treated hamsters against 6 of 23 given ramoplanin.
Endocarditis needs a partner drug
In rabbits with endocarditis from multidrug-resistant Enterococcus faecium, ramoplanin alone lowered spleen and kidney counts but not heart-valve counts; with penicillin it cut valve counts by more than 3 log units. Its bactericidal effect was lost in 50% serum, and the authors noted it would not be available for injection.
A gonorrhoea candidate
Ramoplanin was active against all 14 WHO reference strains of Neisseria gonorrhoeae in vitro and treated infection in Galleria mellonella larvae, an insect model, without signs of toxicity.
Blocks cell-wall synthesis
In Staphylococcus aureus and Bacillus megaterium, ramoplanin caused cell-wall precursors to accumulate and blocked the step after formation of lipid intermediate I; bacteria bound about 5 × 10⁴ molecules per cell, a hundredth of the vancomycin figure, pointing to a different target.
Binds lipid II as a dimer
Enzyme studies found ramoplanin inhibits bacterial transglycosylases by binding their substrate, lipid II, with two ramoplanin molecules per lipid II and an apparent dissociation constant in the nanomolar range.
Crystal structure of the dimer
A 1.4 Å X-ray structure of ramoplanin A2 in a detergent environment showed a tight, highly amphipathic dimer and suggested how it lies against bacterial membranes and recognises lipid II.
Depolarises the membrane at high doses
Ramoplanin bound anionic membrane models more strongly than neutral ones and depolarised Staphylococcus aureus membranes at or above the minimal bactericidal concentration, with marked damage visible under the electron microscope.
Active against resistant C. difficile
Against 105 toxigenic clinical isolates of C. difficile, including 8 with reduced vancomycin susceptibility and 6 resistant to metronidazole, MICs ranged from 0.03 to 0.5 µg/ml, with all isolates susceptible.
Clings to C. difficile spores
After even 30 minutes at a faecal-level concentration (300 µg/ml), spore counts stayed below detection for 28 days, which metronidazole and vancomycin did not achieve; removing the spore's outer coat reversed this, suggesting it binds the coat and kills germinating cells.
Spares Gram-negative gut anaerobes
Against 354 intestinal anaerobes, ramoplanin inhibited 96% of Gram-positive strains at 2 µg/ml or less, including C. difficile and vancomycin-resistant Clostridium innocuum, but MICs for Bacteroides fragilis group, some Fusobacterium and Veillonella were 256 µg/ml or higher.
Kills resistant enterococci
Ramoplanin was active against all 65 enterococcal strains tested, including those highly resistant to vancomycin, penicillin and gentamicin, and killed in a dose-dependent way strains that resisted vancomycin or penicillin combined with gentamicin.
European VRE survey
Of 1,314 clinical enterococci from 13 hospitals in eight countries, 2.9% were vancomycin-resistant, most in Italy and the UK; ramoplanin was active against every VRE isolate, with an MIC90 of 0.5 mg/l.
MRSA from 26 countries
Against 162 MRSA isolates, the MIC90 was 0.5 mg/l and no resistance was found; at 20 mg/l it killed 99.9% of bacteria in under 4 hours.
Resistance can be selected
Serial passage of Staphylococcus aureus in rising concentrations produced a markedly resistant strain that was also less sensitive to vancomycin and nisin and had a thickened wall; susceptibility returned after 18 days without the drug.
Three components, one ring
Chemical, NMR and mass-spectrometry work on the antibiotic from Actinoplanes sp. ATCC 33076 showed three components sharing a depsipeptide ring with two mannose sugars, differing in C8, C9 or C10 fatty-acid side chains.
Dosing Data
Ramoplanin was never approved, so there is no label. These are the oral doses from the one published human trial carded above.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or 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
Unknown: we hold no label and no published test that says what forms or vial sizes Ramoplanin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: oral). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Ramoplanin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Ramoplanin stays intact once mixed.
How it is taken
As it was given in human studies: Oral (Twice daily; Study: gut VRE carriage, phase 2 (lower dose)).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Study: gut VRE carriage, phase 2 (lower dose): 7 days; Study: gut VRE carriage, phase 2 (higher dose): 7 days.
When effects appear: unknown; no source on this page gives a time to effect for Ramoplanin. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Adverse events similar to placebo in the phase 2 VRE trial (PMID 11588692); Minimal adverse effects and no documented drug interactions in the 2005 review (PMID 15784805); In mice, overgrowth of Gram-negative gut bacteria such as Klebsiella (PMID 15155213); Rapid return of VRE after stopping, especially with other anti-anaerobe antibiotics (PMID 11923325). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Ramoplanin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the trials and reviews above”).
Interactions
Unknown: a PubMed search for human interaction studies of Ramoplanin (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 Ramoplanin 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 Ramoplanin's expected mass, 2,554.1 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Discontinued (Never approved: Drugs@FDA and the EMA medicines list hold no record (searched October 28, 2026)). 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
From the trials and reviews above.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Ramoplanin was an investigational antibiotic; it has not been approved anywhere in the sources read.
Frequently Asked Questions
?What is ramoplanin?
A peptide antibiotic with attached sugars and a fatty-acid chain, made by an Actinoplanes bacterium. It kills Gram-positive bacteria by binding lipid II, a cell-wall building block.
?Is ramoplanin approved?
No. It was fast-tracked by the FDA and passed phase 2 trials, but no phase 3 result was published and no regulator has approved it.
?What was it tested for?
Taken by mouth, it was tested to clear vancomycin-resistant enterococci from the gut and to treat C. difficile diarrhoea, where a phase 2 trial found it comparable to vancomycin.
?Does it work against vancomycin-resistant bacteria?
Yes, in the laboratory. It binds a different part of the cell-wall pathway from vancomycin, and every VRE isolate in a European survey was susceptible.
?Why did VRE come back after treatment?
In the phase 2 trial, stool cleared during the week of treatment but most patients were recolonised by a related strain within two to three weeks, more often if they were also given antibiotics active against anaerobes.
References
- [other] PubChem CID 16129628, Ramoplanin A2: formula C119H154ClN21O40, molecular weight 2554.1. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/16129628
- [other] US FDA, Drugs@FDA (openFDA): no application for ramoplanin. Read October 28, 2026.
- [clinical-trial] Wong MT, et al. "Effective suppression of vancomycin-resistant Enterococcus species in asymptomatic gastrointestinal carriers by a novel glycolipodepsipeptide, ramoplanin." Clin Infect Dis, 2001;33(9):1476-82. PMID: 11588692.
- [clinical-trial] Baden LR, et al. "Molecular characterization of vancomycin-resistant Enterococci repopulating the gastrointestinal tract following treatment with a novel glycolipodepsipeptide, ramoplanin." J Clin Microbiol, 2002;40(4):1160-3. PMID: 11923325.
- [review] Fulco P, et al. "Ramoplanin: a topical lipoglycodepsipeptide antibacterial agent." Expert Rev Anti Infect Ther, 2006;4(6):939-45. PMID: 17181409.
- [review] Farver DK, et al. "Ramoplanin: a lipoglycodepsipeptide antibiotic." Ann Pharmacother, 2005;39(5):863-8. PMID: 15784805.
- [review] Montecalvo MA, et al. "Ramoplanin: a novel antimicrobial agent with the potential to prevent vancomycin-resistant enterococcal infection in high-risk patients." J Antimicrob Chemother, 2003;51 Suppl 3:iii31-5. PMID: 12801940.
- [pubmed] Stiefel U, et al. "Efficacy of oral ramoplanin for inhibition of intestinal colonization by vancomycin-resistant enterococci in mice." Antimicrob Agents Chemother, 2004;48(6):2144-8. PMID: 15155213.
- [pubmed] Freeman J, et al. "Comparison of the efficacy of ramoplanin and vancomycin in both in vitro and in vivo models of clindamycin-induced Clostridium difficile infection." J Antimicrob Chemother, 2005;56(4):717-25. PMID: 16143709.
- [pubmed] Landman D, et al. "Treatment of experimental endocarditis caused by multidrug resistant Enterococcus faecium with ramoplanin and penicillin." J Antimicrob Chemother, 1996;37(2):323-9. PMID: 8707742.
- [pubmed] Gestels Z, et al. "Ramoplanin as a novel therapy for Neisseria gonorrhoeae infection: an in vitro and in vivo study in Galleria mellonella." J Med Microbiol, 2024;73(1). PMID: 38214499.
- [pubmed] Somner EA, et al. "Inhibition of peptidoglycan biosynthesis by ramoplanin." Antimicrob Agents Chemother, 1990;34(3):413-9. PMID: 2334153.
- [pubmed] Hu Y, et al. "Ramoplanin inhibits bacterial transglycosylases by binding as a dimer to lipid II." J Am Chem Soc, 2003;125(29):8736-7. PMID: 12862463.
- [pubmed] Hamburger JB, et al. "A crystal structure of a dimer of the antibiotic ramoplanin illustrates membrane positioning and a potential Lipid II docking interface." Proc Natl Acad Sci U S A, 2009;106(33):13759-64. PMID: 19666597.
- [pubmed] Cheng M, et al. "Ramoplanin at bactericidal concentrations induces bacterial membrane depolarization in Staphylococcus aureus." Antimicrob Agents Chemother, 2014;58(11):6819-27. PMID: 25182650.
- [pubmed] Peláez T, et al. "In vitro activity of ramoplanin against Clostridium difficile, including strains with reduced susceptibility to vancomycin or with resistance to metronidazole." Antimicrob Agents Chemother, 2005;49(3):1157-9. PMID: 15728918.
- [pubmed] Kraus CN, et al. "Ambush of Clostridium difficile spores by ramoplanin: activity in an in vitro model." Antimicrob Agents Chemother, 2015;59(5):2525-30. PMID: 25691641.
- [pubmed] Citron DM, et al. "In vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, bacitracin, and four other antimicrobials against intestinal anaerobic bacteria." Antimicrob Agents Chemother, 2003;47(7):2334-8. PMID: 12821492.
- [pubmed] Johnson CC, et al. "Bactericidal activity of ramoplanin against antibiotic-resistant enterococci." Antimicrob Agents Chemother, 1992;36(10):2342-5. PMID: 1444316.
- [pubmed] Goossens H, et al. "European survey of vancomycin-resistant enterococci in at-risk hospital wards and in vitro susceptibility testing of ramoplanin against these isolates." J Antimicrob Chemother, 2003;51 Suppl 3:iii5-12. PMID: 12801937.
- [pubmed] Brumfitt W, et al. "Ramoplanin versus methicillin-resistant Staphylococcus aureus: in vitro experience." Drugs Exp Clin Res, 1990;16(8):377-83. PMID: 2097143.
- [pubmed] Schmidt JW, et al. "Generation of ramoplanin-resistant Staphylococcus aureus." FEMS Microbiol Lett, 2010;310(2):104-11. PMID: 20659164.
- [pubmed] Ciabatti R, et al. "Ramoplanin (A-16686), a new glycolipodepsipeptide antibiotic. III. Structure elucidation." J Antibiot (Tokyo), 1989;42(2):254-67. PMID: 2597278.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Regulatory and trial-registry status comes from Drugs@FDA (openFDA), the EMA medicines list and ClinicalTrials.gov, searched October 28, 2026; the formula and weight are PubChem's for ramoplanin A2. 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.