Surotomycin
A gut-confined relative of daptomycin built to treat C. difficile, which did no better than vancomycin in two phase 3 trials and was dropped
Surotomycin is a semisynthetic cyclic lipopeptide made from a core produced by the bacterium Streptomyces roseosporus, the same source as daptomycin. Swallowed, almost none of it is absorbed, so it stays in the bowel where Clostridioides difficile lives. A phase 2 trial suggested fewer relapses than with vancomycin. Two phase 3 trials with about 1,150 patients did not bear that out: the first failed to show it was even as good as vancomycin, and the second matched vancomycin at the end of treatment but was not better afterwards. Development stopped, and it was never approved.
Used in human trials: 250 mg, Twice daily, Oral (Phase 3 trials: adults with C. difficile infection (comparator: ora...) 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?
Clostridioides difficile infection is a bowel infection, usually after other antibiotics have wiped out the normal gut flora, and its biggest problem is relapse: a large share of patients who recover get it again within weeks. Antibiotics that kill C. difficile while sparing the rest of the gut bacteria were seen as a way to cut that relapse rate. Surotomycin was one of several such candidates in the 2010s, alongside cadazolid, ridinilazole and fidaxomicin, the one that did reach the market.
Chemically, surotomycin is a cousin of daptomycin, the intravenous antibiotic for serious Gram-positive infections. Chemists at Cubist kept daptomycin's ring of amino acids, made by Streptomyces roseosporus fermentation, and swapped in a range of new lipid tails, testing how tail length and aromatic groups changed activity. The compound they chose was about four times more potent than daptomycin against C. difficile in the laboratory and protected hamsters at a low oral dose. It acts on the bacterial membrane: it dissipates the membrane potential and kills C. difficile both while it is growing and when it is in the stationary phase, which vancomycin and metronidazole do poorly. It does not kill spores.
Phase 1 studies in healthy volunteers confirmed that it stays in the gut. Even at 4,000 mg in a single dose, peak blood levels were below 90 ng/mL, less than 0.01% of the dose appeared in urine, and stool held concentrations thousands of times the MIC. At up to 1,000 mg twice daily for two weeks, it lowered counts of Gram-positive gut bacteria but left Bacteroides and other Gram-negative groups largely alone.
In a phase 2 trial, cure rates at the end of ten days were similar for two surotomycin doses and vancomycin, but recurrences were fewer with 250 mg twice daily (17.2% against 35.6%). That result drove two phase 3 trials, each comparing 250 mg twice daily with oral vancomycin 125 mg four times daily for ten days. In the first (570 patients), surotomycin's end-of-treatment cure rate was 79.0% against 83.6% for vancomycin, and it failed to meet the non-inferiority margin for the primary endpoint and for sustained response. In the second (577 patients), clinical response at the end of treatment was 83.4% against 82.1%, which met non-inferiority, but sustained response 30 to 40 days later (63.3% against 59.0%) was not superior, and superiority was the point of the drug.
Merck, which had acquired Cubist, ended development; a 2017 paper on the phase 2 microbiome substudy states that surotomycin was no longer in development because of the failed phase 3 results. Later meta-analyses pooling the three trials found no significant difference from vancomycin in cure, sustained response or overall recurrence. It is not approved anywhere and no trial has been registered since. Its trials are still cited, for their large collections of C. difficile strains and as a lesson in how a promising phase 2 relapse signal can disappear at scale.
Mechanism of Action
Surotomycin is a membrane-active lipopeptide: its lipid tail anchors it in the bacterial membrane, collapsing the membrane potential of C. difficile, and because it is barely absorbed it stays concentrated in the bowel.
Gram-positive selectivity
It hits C. difficile and other Gram-positive gut bacteria while largely sparing Bacteroides and other Gram-negative groups in volunteers and patients.
Gut-confined exposure
Plasma levels stayed in the low ng/mL range and almost none reached the urine, while stool concentrations far exceeded the MIC.
Published Research
These are studies of surotomycin read from their PubMed abstracts: the phase 1, 2 and 3 clinical trials and their microbiome and strain substudies, two meta-analyses, laboratory work on how it kills C. difficile and how resistance could arise, two animal studies and a development review.
First phase 3 trial: not as good as vancomycin
In 570 adults with toxin-confirmed C. difficile infection, randomised and double-blind, oral surotomycin 250 mg twice daily or vancomycin 125 mg four times daily for 10 days gave end-of-treatment cure rates of 79.0% and 83.6%. Neither that primary endpoint nor sustained response through day 40 to 50 (60.6% against 61.4%) met the non-inferiority criteria. Both drugs were generally well tolerated.
Second phase 3 trial: equal at first, not better later
In 577 patients randomised to surotomycin 250 mg twice daily or vancomycin 125 mg four times daily for 10 days, clinical response at the end of treatment was 83.4% against 82.1%, meeting non-inferiority. Sustained response 30 to 40 days after treatment (63.3% against 59.0%) and response over time were not superior to vancomycin. Both were generally well tolerated.
Phase 2: fewer relapses than vancomycin
Patients received surotomycin 125 mg or 250 mg twice daily or vancomycin 125 mg four times daily for 10 days. Cure rates were 92.4%, 86.6% and 89.4%. Recurrence was 27.9%, 17.2% and 35.6%; only the 250 mg dose differed significantly from vancomycin. Sustained response was 66.7%, 70.1% and 56.1%, and adverse events were similar across arms.
Phase 2 microbiome substudy
In 26 patients at one centre, surotomycin 250 mg twice daily and vancomycin both cut faecal C. difficile to low levels within 4 to 10 days; it stayed detectable in 3 of 9 on 125 mg. Vancomycin lowered Bacteroidetes and Prevotella by 2.5 to 3.2 log units while surotomycin left them unchanged or higher. The authors note development had stopped after the phase 3 results.
Phase 1: very little reaches the blood
Healthy volunteers took single doses of 500 to 4,000 mg or 250 to 1,000 mg twice daily for 14 days, with placebo controls. Peak plasma levels after single doses ranged from 10.5 to 86.7 ng/mL, peaking 6 to 12 hours after dosing, with some build-up over 14 days. Under 0.01% of a dose reached the urine, while stool levels averaged 6,394 micrograms per gram. Adverse events were mild to moderate.
Phase 1: modest effect on gut flora
Thirty volunteers took 250, 500 or 1,000 mg twice daily or placebo for 14 days. Total stool bacteria fell by 1 to 2 log units, with drops in clostridia, lactobacilli, bifidobacteria and enterococci, while Enterobacteriaceae and the Bacteroides fragilis group persisted. Enterococcal MICs did not change and no vancomycin-resistant enterococci appeared.
The strains behind the phase 3 trials
Of 992 C. difficile isolates from the two phase 3 trials, 922 were typed. The epidemic BI/RT027 strain was the most common (20.3%), highest in Europe and Canada and rare in Australia and New Zealand, and carried the most resistance to metronidazole, vancomycin and moxifloxacin.
Meta-analysis of the three randomised trials
Pooling 1,280 patients from three trials of surotomycin 250 mg twice daily against vancomycin, cure after 10 days, sustained response and overall recurrence did not differ significantly. Recurrence with the BI/NAP1/027 strain was lower with surotomycin (pooled odds ratio 0.35), a subgroup finding.
Discovery and development
Describes surotomycin as a cyclic lipopeptide with a core from Streptomyces roseosporus fermentation that disrupts the C. difficile membrane in growing and stationary cells and spares Gram-negative gut bacteria. Low oral bioavailability lets gut levels far exceed the MIC; it worked in hamsters and, at 250 mg twice daily in phase 2, had fewer recurrences than vancomycin.
Choosing the lipid tail
A series of semisynthetic lipopeptides with different acyl tails showed that tail lipophilicity, length and aromatic groups set activity. The lead, surotomycin, had an MIC90 of 0.5 against 2 micrograms per ml for daptomycin against C. difficile, including epidemic strains, and protected hamsters at an oral dose of 0.5 mg/kg.
Kills C. difficile through its membrane
Surotomycin killed C. difficile in both growing and stationary cultures at up to 16 times the MIC, stopped DNA, RNA, protein and cell-wall synthesis, and collapsed the membrane potential without making the membrane permeable to propidium iodide, the pattern of a membrane-active antibiotic.
Activity against spores and stationary cells
Like metronidazole and vancomycin, surotomycin did not kill spores and killed growing cells at 8 times the MIC. Unlike them, at 80 times the MIC it killed stationary-phase cells, and did so without bursting them.
Lower toxin output after exposure
Against the epidemic R20291 strain, surotomycin at 4 and 40 times the MIC cut live cells by about 4 log units over 72 hours and reduced toxin A and B by 77% and 68% at 48 hours, lowering the inflammatory IL-8 response of gut cells. Electron microscopy showed broken cell walls at high concentrations.
Sub-lethal amounts and virulence
At concentrations too low to kill, surotomycin and vancomycin both briefly raised early toxin A and B production in several strains, an effect gone by 24 to 48 hours, and both suppressed spore formation.
Resistance is rare and slow
Spontaneous resistance in C. difficile and enterococci was below detection (under 1 in 100 million). Serial passage over 15 days raised MICs 4- to 64-fold depending on the strain, with no cross-resistance to vancomycin, rifampin, ampicillin, metronidazole or moxifloxacin, and killing stayed rapid.
Mutations behind reduced susceptibility
Sequencing C. difficile and enterococci passaged to lower surotomycin susceptibility found mutations in genes such as cardiolipin synthase, FabK and FtsH2 in C. difficile; the enterococcal mutations overlapped those known for daptomycin resistance.
Activity against Spanish clinical isolates
Across 100 toxigenic C. difficile isolates collected in Spain in 2013, surotomycin MICs ranged up to 2 mg/L, with MIC50 and MIC90 of 0.25 and 0.5 mg/L. It stayed active against isolates with reduced susceptibility to metronidazole or vancomycin; ribotype 078/126 had the highest MICs.
Gut model of infection
In a three-stage chemostat model seeded with human faeces and C. difficile spores, surotomycin given after clindamycin-induced infection cut vegetative cells to near detection limits and made toxin undetectable within days, but growth and toxin returned 11 to 15 days after it stopped. It spared the Bacteroides fragilis group, and no reduced susceptibility emerged.
Effects on resistant gut colonisers in mice
In mice, oral vancomycin promoted overgrowth of vancomycin-resistant enterococci and an ESBL-producing Klebsiella; surotomycin promoted the Klebsiella but not the enterococci, and it suppressed enterococcal colonisation that was already established.
Dosing Data
Surotomycin was never approved. These are the amounts given in its published human trials, as stated in their abstracts. The 250 mg twice-daily course is the one tested against vancomycin in phase 3, where it did not show the benefit it was developed for.
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 Surotomycin 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 Surotomycin, 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 Surotomycin stays intact once mixed.
How it is taken
As it was given in human studies: Oral (Twice daily; Phase 3 trials: adults with C. difficile infection (comparator: oral vancomycin)).
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: Phase 3 trials: adults with C. difficile infection (comparator: oral vancomycin): 10 days; Phase 2 trial: lower-dose arm: 10 days; Phase 1: healthy volunteers, multiple ascending doses: 14 days.
When effects appear: unknown; no source on this page gives a time to effect for Surotomycin. 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: Generally well tolerated in both phase 3 trials, similar to vancomycin (PMIDs 28480267, 28961905); Adverse event rates similar to vancomycin in phase 2 (PMID 27432604); Mild to moderate adverse events only in phase 1 volunteers (PMID 28347318); Lower counts of several Gram-positive gut bacteria during treatment (PMID 26787687). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Surotomycin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the clinical trials above”).
Interactions
Unknown: a PubMed search for human interaction studies of Surotomycin (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 Surotomycin 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 Surotomycin's expected mass, 1,680.7 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 clinical trials above.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Surotomycin was an investigational antibiotic whose development ended after phase 3; it is not approved anywhere in the sources read.
Frequently Asked Questions
?What was surotomycin for?
Treating Clostridioides difficile infection of the bowel. It was taken by mouth and stayed in the gut, where the infection is.
?Why was it dropped?
Its selling point was fewer relapses than vancomycin, seen in phase 2. In phase 3, one trial failed to show it was as good as vancomycin and the other showed it was as good but not better, so development ended.
?How is it related to daptomycin?
Both are built on the same cyclic peptide core from Streptomyces roseosporus. Surotomycin has a different lipid tail, chosen for activity against C. difficile, and is given by mouth rather than intravenously.
?Is it absorbed into the blood?
Barely. In healthy volunteers peak blood levels were in the nanogram range and under 0.01% of a dose appeared in urine.
?Did resistance develop?
Spontaneous resistance was undetectable in the laboratory, though repeated exposure raised MICs several-fold in some strains, with mutations overlapping daptomycin resistance in enterococci.
?Can I get surotomycin?
No. It was never approved and no product exists. Approved options for C. difficile include vancomycin and fidaxomicin, chosen by a doctor.
References
- [clinical-trial] Boix V, et al. "Primary Outcomes From a Phase 3, Randomized, Double-Blind, Active-Controlled Trial of Surotomycin in Subjects With Clostridium difficile Infection." Open Forum Infect Dis, 2017;4(1):ofw275. PMID: 28480267.
- [clinical-trial] Daley P, et al. "Surotomycin versus vancomycin in adults with Clostridium difficile infection: primary clinical outcomes from the second pivotal, randomized, double-blind, Phase 3 trial." J Antimicrob Chemother, 2017;72(12):3462-3470. PMID: 28961905.
- [clinical-trial] Lee CH, et al. "Surotomycin versus vancomycin for Clostridium difficile infection: Phase 2, randomized, controlled, double-blind, non-inferiority, multicentre trial." J Antimicrob Chemother, 2016;71(10):2964-71. PMID: 27432604.
- [clinical-trial] Cannon K, et al. "Enteric microbiome profiles during a randomized Phase 2 clinical trial of surotomycin versus vancomycin for the treatment of Clostridium difficile infection." J Antimicrob Chemother, 2017;72(12):3453-3461. PMID: 28927227.
- [clinical-trial] Chandorkar G, et al. "Pharmacokinetics of surotomycin from phase 1 single and multiple ascending dose studies in healthy volunteers." BMC Pharmacol Toxicol, 2017;18(1):24. PMID: 28347318.
- [clinical-trial] Citron DM, et al. "Impact of Surotomycin on the Gut Microbiota of Healthy Volunteers in a Phase 1 Clinical Trial." Antimicrob Agents Chemother, 2016;60(4):2069-74. PMID: 26787687.
- [clinical-trial] Cheknis A, et al. "Characterization of Clostridioides difficile isolates recovered from two Phase 3 surotomycin treatment trials by restriction endonuclease analysis, PCR ribotyping and antimicrobial susceptibilities." J Antimicrob Chemother, 2020;75(11):3120-3125. PMID: 32747931.
- [review] Muhammad A, et al. "Surotomycin (A Novel Cyclic Lipopeptide) vs. Vancomycin for the Treatment of Clostridioides difficile Infection: A Systematic Review and Meta-analysis." Curr Clin Pharmacol, 2019;14(3):166-174. PMID: 30924421.
- [review] Kravets AM, et al. "Microbiome-preserving antibiotics for the treatment of Clostridioides difficile infection: a systematic review and meta-analysis." Tech Coloproctol, 2023;28(1):20. PMID: 38112980.
- [review] Knight-Connoni V, et al. "Discovery and development of surotomycin for the treatment of Clostridium difficile." J Ind Microbiol Biotechnol, 2016;43(2-3):195-204. PMID: 26670919.
- [pubmed] Yin N, et al. "Structure-Activity Relationship Studies of a Series of Semisynthetic Lipopeptides Leading to the Discovery of Surotomycin, a Novel Cyclic Lipopeptide Being Developed for the Treatment of Clostridium difficile-Associated Diarrhea." J Med Chem, 2015;58(12):5137-42. PMID: 25993059.
- [pubmed] Alam MZ, et al. "Mode of action and bactericidal properties of surotomycin against growing and nongrowing Clostridium difficile." Antimicrob Agents Chemother, 2015;59(9):5165-70. PMID: 26055381.
- [pubmed] Bouillaut L, et al. "Effects of surotomycin on Clostridium difficile viability and toxin production in vitro." Antimicrob Agents Chemother, 2015;59(7):4199-205. PMID: 25941230.
- [pubmed] Endres BT, et al. "Evaluating the Effects of Surotomycin Treatment on Clostridium difficile Toxin A and B Production, Immune Response, and Morphological Changes." Antimicrob Agents Chemother, 2016;60(6):3519-23. PMID: 27021314.
- [pubmed] Aldape MJ, et al. "Sub-lethal doses of surotomycin and vancomycin have similar effects on Clostridium difficile virulence factor production in vitro." J Med Microbiol, 2018;67(12):1689-1697. PMID: 30307842.
- [pubmed] Mascio CT, et al. "Surotomycin demonstrates low in vitro frequency of resistance and rapid bactericidal activity in Clostridium difficile, Enterococcus faecalis, and Enterococcus faecium." Antimicrob Agents Chemother, 2014;58(7):3976-82. PMID: 24798273.
- [pubmed] Adams HM, et al. "Mutations associated with reduced surotomycin susceptibility in Clostridium difficile and Enterococcus species." Antimicrob Agents Chemother, 2015;59(7):4139-47. PMID: 25941217.
- [pubmed] Reigadas E, et al. "In vitro activity of surotomycin against contemporary clinical isolates of toxigenic Clostridium difficile strains obtained in Spain." J Antimicrob Chemother, 2015;70(8):2311-5. PMID: 25876881.
- [pubmed] Chilton CH, et al. "Efficacy of surotomycin in an in vitro gut model of Clostridium difficile infection." J Antimicrob Chemother, 2014;69(9):2426-33. PMID: 24816211.
- [pubmed] Deshpande A, et al. "Effect of Surotomycin, a Novel Cyclic Lipopeptide Antibiotic, on Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice." Antimicrob Agents Chemother, 2016;60(6):3333-9. PMID: 26976870.
- [other] PubChem CID 46700778, Surotomycin: formula C77H101N17O26, molecular weight 1680.7. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/46700778
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT01597505 and NCT01598311 (phase 3, completed), NCT02835105 and NCT02835118 (phase 1, completed).
- [other] US FDA, Drugs@FDA (openFDA): no application for surotomycin. Read October 28, 2026.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026; a PubMed search for surotomycin in titles and abstracts returned 45 records. Registry and regulatory status come from ClinicalTrials.gov, Drugs@FDA (openFDA) and the EMA medicines list, read 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.