# Mupirocin

**Mupirocin** (also called pseudomonic acid A, marketed as Bactroban and Centany) is a topical antibiotic produced by the soil bacterium *Pseudomonas fluorescens* that kills staphylococci and streptococci by inhibiting bacterial protein synthesis, and is used to treat impetigo and to eradicate *Staphylococcus aureus*, including MRSA, from the skin and nostrils.<sup>[1](https://ueaeprints.uea.ac.uk/id/eprint/91869/1/2023ListonJDPhD.pdf)</sup><sup> • </sup><sup>[2](https://www.nature.com/articles/nrmicro2278)</sup> Discovered in 1971, it appears on the World Health Organization's list of essential medicines.<sup>[1](https://ueaeprints.uea.ac.uk/id/eprint/91869/1/2023ListonJDPhD.pdf)</sup>

| Key fact | Detail |
|---|---|
| Origin | Natural polyketide antibiotic (pseudomonic acid) from *Pseudomonas fluorescens*, discovered in 1971<sup>[1](https://ueaeprints.uea.ac.uk/id/eprint/91869/1/2023ListonJDPhD.pdf)</sup> |
| Mechanism | Reversibly and specifically binds bacterial isoleucyl-tRNA synthetase, blocking protein synthesis; no cross-resistance with other antibiotic classes<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> |
| Approved use (US) | Topical treatment of impetigo due to *Staphylococcus aureus* and *Streptococcus pyogenes* in patients 2 months of age and older; 2% ointment applied three times daily<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> |
| Other major use | Nasal and skin decolonization of MRSA and methicillin-susceptible *S. aureus* carriage in patients and healthcare personnel<sup>[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC11633570/)</sup> |
| Efficacy in impetigo | Equal to fusidic acid (RR 1.03, 95% CI 0.95–1.11) and slightly better than oral erythromycin (RR 1.07, 95% CI 1.01–1.13) for limited disease<sup>[5](https://www.cochrane.org/evidence/CD003261_interventions-skin-infection-impetigo)</sup> |
| Resistance | Low-level (MIC 8–256 mcg/mL) from a modified target enzyme; high-level (MIC ≥512 mcg/mL) from acquired alternate synthetases encoded by *mupA* and *mupB*<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup><sup> • </sup><sup>[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3318397/)</sup> |
| Why topical only | Rapidly metabolized after oral or intravenous administration to monic acid, which has no antibacterial activity; IV half-life 20–40 minutes<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> |

## Chemistry and mechanism

Mupirocin is a mixture of A–D pseudomonic acids, crotonic acid derivatives produced by *Pseudomonas fluorescens* through modular polyketide synthases (bacterial enzymes that assemble complex antibiotic molecules).<sup>[7](https://www.sciencedirect.com/science/article/pii/S0753332218357901)</sup> The compound has the molecular formula C26H44O9 and a molecular weight of 500.62.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> Its biosynthesis is carried out by type I multifunctional polyketide synthases and tailoring enzymes encoded in a 75 kb gene cluster, and the producing strain protects itself with a second, resistant copy of its housekeeping isoleucyl-tRNA synthetase.<sup>[2](https://www.nature.com/articles/nrmicro2278)</sup><sup> • </sup><sup>[1](https://ueaeprints.uea.ac.uk/id/eprint/91869/1/2023ListonJDPhD.pdf)</sup>

The drug's target is bacterial isoleucyl-tRNA synthetase, the enzyme that charges transfer RNA with isoleucine. Mupirocin's epoxide side chain structurally resembles isoleucine and binds the isoleucine-specific pocket of the enzyme, reversibly and specifically blocking protein synthesis.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup><sup> • </sup><sup>[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3318397/)</sup> Because of this mode of action, mupirocin shows no cross-resistance with other classes of antimicrobial agents.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> It is bactericidal at concentrations typically achieved by topical administration, is more than 97% protein bound, and is active against some gram-positive bacteria including MRSA and some gram-negative bacteria.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup>

## Clinical use

**Impetigo.** In the United States, 2% mupirocin ointment is indicated for impetigo due to *S. aureus* and *S. pyogenes* in adults and children 2 months of age and older, applied three times daily, with re-evaluation if there is no response within 3 to 5 days.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> A 2012 Cochrane review of 68 randomized trials found that topical mupirocin and topical fusidic acid, the two most studied topical antibiotics, were equally effective (RR 1.03, 95% CI 0.95 to 1.11, in 4 studies with 440 participants) and that both were at least as effective as oral antibiotics for limited disease; topical mupirocin was slightly superior to oral erythromycin (RR 1.07, 95% CI 1.01 to 1.13, in 10 studies with 581 participants).<sup>[5](https://www.cochrane.org/evidence/CD003261_interventions-skin-infection-impetigo)</sup> Side effects of topical treatment were mild and infrequent, mainly itching, burning, or staining, while oral antibiotics caused gastrointestinal complaints in 2% to 30% of participants depending on the drug.<sup>[5](https://www.cochrane.org/evidence/CD003261_interventions-skin-infection-impetigo)</sup> In a pivotal trial comparing two mupirocin ointments applied three times daily for 7 days, clinical efficacy rates at follow-up were 94% and 95%, with pathogen eradication rates of 98% for both.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> Because of resistance concerns, UK primary care guidance reserves mupirocin for MRSA and advises against first-line use for impetigo.<sup>[8](https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/362394/PHE_Primary_Care_guidance_09_10_14.pdf)</sup>

**Decolonization.** Mupirocin is used mainly to decolonize MRSA and methicillin-susceptible *S. aureus* from patients and healthcare personnel, particularly in the nose, and to prevent recurring infections and control outbreaks.<sup>[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC11633570/)</sup><sup> • </sup><sup>[7](https://www.sciencedirect.com/science/article/pii/S0753332218357901)</sup> Where MRSA isolates are epidemic, it may be used as a choice drug for nasal decolonization.<sup>[7](https://www.sciencedirect.com/science/article/pii/S0753332218357901)</sup>

**Why it cannot be given systemically.** After oral or intravenous administration, mupirocin is rapidly metabolized, and its principal metabolite, monic acid, has no antibacterial activity; the intravenous elimination half-life is 20 to 40 minutes for mupirocin and 30 to 80 minutes for monic acid.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> Systemic absorption through intact human skin is at most 1.25% of the administered dose.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> Gram-negative organisms, anaerobes, and fungi are not susceptible, and healthy skin flora such as *Micrococcus*, *Corynebacteria*, and *Propionibacteria* are not disrupted by its use.<sup>[1](https://ueaeprints.uea.ac.uk/id/eprint/91869/1/2023ListonJDPhD.pdf)</sup>

## Resistance

Resistance has increased with use, particularly among MRSA isolates, and rates differ by geographic area.<sup>[7](https://www.sciencedirect.com/science/article/pii/S0753332218357901)</sup> Three susceptibility categories are defined for *S. aureus*: susceptible at a MIC of 4 mcg/mL or below, low-level resistance at 8 to 256 mcg/mL, and high-level resistance at 512 mcg/mL or above.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup><sup> • </sup><sup>[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3318397/)</sup>

Low-level resistance results from point mutations in the native isoleucyl-tRNA synthetase gene (*ileS*), which alter the drug's binding to its target.<sup>[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC11633570/)</sup> High-level resistance is mediated by acquired genes encoding alternate isoleucyl-tRNA synthetases: *mupA* (also called *ileS2*), carried on conjugative plasmids, and *mupB*, a 3,102 bp gene sharing 65.5% sequence identity with *mupA*, first identified in a clinical MRSA strain in Canada.<sup>[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC11633570/)</sup><sup> • </sup><sup>[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3318397/)</sup> Therapy failure has been associated with strains showing high-level resistance (MIC above 500 mcg/mL), while low-level resistance is more common.<sup>[9](https://pubmed.ncbi.nlm.nih.gov/7657989/)</sup> In one decolonization program, the rate of high-level mupirocin resistance rose from 21% before treatment to 43% after 5 days of mupirocin and chlorhexidine treatment, with 99.5% of that resistance mediated by *mupA*.<sup>[10](https://pmc.ncbi.nlm.nih.gov/articles/PMC5475228/)</sup> Mupirocin has shown clinical efficacy against MRSA, but bacterial culture is recommended to rule out resistance.<sup>[11](https://pubmed.ncbi.nlm.nih.gov/33726585/)</sup>

## Safety

Reported local adverse reactions in a 300-patient trial included application site reactions and pruritus, each in 1% of patients; contact dermatitis and furunculosis, each in 0.7%; and exfoliative dermatitis and rash, each in 0.3%.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> Systemic allergic reactions, including anaphylaxis, urticaria, angioedema, and generalized rash, have been reported with mupirocin formulations, and prolonged use may result in overgrowth of nonsusceptible microorganisms, including fungi.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> The ointment is not intended for ophthalmic use, nasal use, or mucosal surfaces.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup>

## Regulatory history

Mupirocin was first approved in the United States in 1987.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)</sup> In a letter dated January 5, 2022, GlaxoSmithKline requested withdrawal of the new drug application for BACTROBAN (mupirocin) nasal ointment, 2%; in December 2025 the FDA determined that the product had not been withdrawn from sale for reasons of safety or effectiveness, a determination that allows approval of generic mupirocin nasal ointment applications if other requirements are met.<sup>[12](https://www.govinfo.gov/content/pkg/FR-2025-12-12/pdf/FR-2025-12-12.pdf)</sup>

## References

1. [Liston, J. (2023). PhD thesis, University of East Anglia (on aminoacyl-tRNA synthetase inhibitors, including mupirocin)](https://ueaeprints.uea.ac.uk/id/eprint/91869/1/2023ListonJDPhD.pdf)
2. [Thomas CM, Hothersall J, Willis CL, Simpson TJ (2010). Resistance to and synthesis of the antibiotic mupirocin. Nature Reviews Microbiology 8, 281–289.](https://www.nature.com/articles/nrmicro2278)
3. [CENTANY (mupirocin) ointment, 2% — Full Prescribing Information, FDA, revised 7/2025](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/050788s009lbl.pdf)
4. [Mechanisms of Bacterial Resistance to Antimicrobial Agents (resistance to mupirocin section), PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC11633570/)
5. [Koning S et al. (2012). Interventions for the skin infection impetigo. Cochrane Database of Systematic Reviews, Issue 1, CD003261.](https://www.cochrane.org/evidence/CD003261_interventions-skin-infection-impetigo)
6. [MupB, a New High-Level Mupirocin Resistance Mechanism in Staphylococcus aureus, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3318397/)
7. [A review on mechanism of action, resistance, synergism, and clinical implications of mupirocin against Staphylococcus aureus. Biomedicine & Pharmacotherapy 109, 1809–1818 (2019).](https://www.sciencedirect.com/science/article/pii/S0753332218357901)
8. [Public Health England. Management of infection guidance for primary care](https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/362394/PHE_Primary_Care_guidance_09_10_14.pdf)
9. [Bradley SF et al. (1995). Mupirocin resistance: clinical and molecular epidemiology. Infect Control Hosp Epidemiol 16(6), 354–8.](https://pubmed.ncbi.nlm.nih.gov/7657989/)
10. [Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC5475228/)
11. [A comparative review of current topical antibiotics for impetigo (2021), PubMed](https://pubmed.ncbi.nlm.nih.gov/33726585/)
12. [Federal Register Vol. 90, No. 237 (December 12, 2025). Determination That BACTROBAN (Mupirocin) Nasal Ointment, 2%, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness](https://www.govinfo.gov/content/pkg/FR-2025-12-12/pdf/FR-2025-12-12.pdf)

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*Topic: Encyclopedia › Life and health › Human health and medicine › Medicines and therapeutics › Anti-infective drugs and resistance › Antibacterial drugs*

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