Mupirocin is a prescription topical antibiotic widely used for treating bacterial skin infections and decolonizing specific bacteria from the nasal passages. Mupirocin’s unique properties stem from a chemical structure and mechanism of action distinct from nearly all other antibiotics, giving it a unique place in dermatology and infection control.
A Unique Chemical Structure
Mupirocin is chemically classified as a monoxycarbolic acid, an antibiotic structure that is not related to common drug families like penicillins, cephalosporins, or macrolides. The drug was originally isolated in the 1970s from the fermentation products of the bacterium Pseudomonas fluorescens. This natural origin and subsequent unique chemical modification make it a pseudomonic acid derivative, with pseudomonic acid A constituting over 90% of the active compound.
This structural novelty is a major therapeutic advantage because it prevents the development of cross-resistance with other established classes of antibiotics. Bacteria that have become resistant to widely used systemic antibiotics often remain susceptible to mupirocin, preserving its utility for treating difficult-to-manage infections.
How Mupirocin Stops Bacterial Growth
Mupirocin works by inhibiting the enzyme isoleucyl-tRNA synthetase (IleRS) inside the bacterial cell. This enzyme is responsible for linking the amino acid isoleucine to its specific transfer RNA (tRNA) molecule, a process that must occur before the isoleucine can be incorporated into new proteins. Mupirocin mimics the structure of the isoleucyl-tRNA intermediate, allowing it to bind reversibly and specifically to the bacterial IleRS enzyme.
By blocking this enzyme, the antibiotic prevents the formation of isoleucyl-tRNA, which effectively halts the bacteria’s ability to synthesize new proteins. Without the ability to create new proteins, which are necessary for cell structure, function, and reproduction, the bacteria’s growth is stunted, and cell death eventually occurs.
The IleRS enzyme in human cells has a different structure than the bacterial version, which means mupirocin selectively attacks the bacterial process without interfering with protein synthesis in human cells. This specificity helps to minimize systemic side effects, which is a significant benefit for a topical drug. At the high concentrations achieved with topical application, mupirocin is bactericidal, meaning it actively kills the bacteria.
Primary Uses and Administration
Mupirocin is formulated as a 2% ointment or cream and is used exclusively for localized treatment, as it is rapidly metabolized and rendered inactive if taken orally. Any absorbed mupirocin is quickly broken down into an inactive metabolite called monic acid, which is eliminated through the kidneys. This rapid systemic metabolism is why the drug is applied only to the skin or the mucous membranes inside the nose.
The drug has two primary indications in clinical practice. The first is the treatment of primary skin infections, such as impetigo, which is commonly caused by Staphylococcus aureus and Streptococcus pyogenes. For this use, the ointment is typically applied to the affected area three times a day for a period of three to five days.
The second, and arguably more significant, application is the eradication of nasal carriage of S. aureus, particularly MRSA, in patients and healthcare workers. Staphylococcus aureus often colonizes the nasal passages without causing infection, but these individuals can spread the bacteria to others or develop a serious infection themselves. The intranasal formulation of mupirocin is applied inside each nostril twice daily for five days as part of a comprehensive infection control strategy to decolonize the bacteria. This targeted use is a standard procedure in high-risk settings, such as hospitals, to reduce the incidence of MRSA infections.
Preventing Resistance and Side Effects
The widespread and repeated use of mupirocin, particularly for MRSA decolonization, has unfortunately led to the emergence of mupirocin resistance, which is a growing concern for infection control. Resistance typically occurs through the acquisition of a gene called mupA, which allows the bacteria to produce a modified isoleucyl-tRNA synthetase that is not affected by the drug.
To minimize the development of resistance, it is important to use the antibiotic only as prescribed and for the full duration of treatment. Using the ointment for extended periods or for conditions that do not require an antibiotic increases the selection pressure on bacteria, raising the risk of resistance.
When used appropriately, side effects are generally mild and localized to the application site, as very little of the drug enters the bloodstream. Common reactions include local irritation such as burning, stinging, pain, itching, or redness of the treated skin. Patients should discontinue use and consult a healthcare provider if severe irritation or signs of a serious allergic reaction, such as trouble breathing or swelling, occur.