Mupirocin

What is mupirocin?

Mupirocin is a chemically synthesised antibiotic, classified under the ATC code D06AX09 as an antibacterial for topical use.^[1] It belongs to a group of medicines that work directly on the skin and mucous membranes to stop bacterial growth. The substance appears in the EU trial register under the names Impetine 20 mg/g Gel and Bactroban 20 mg/g pomada, and it is authorised as a medicine in Portugal and Spain.^[1] The marketing authorisation holders are Laboratorios Ojer Pharma, S.L. and GlaxoSmithKline, S.A.^[1] In the United States, mupirocin ointment has been approved since 1987.^[4]

How does mupirocin work?

Mupirocin is an RNA synthetase inhibitor antibacterial.^[4] It blocks an enzyme that bacteria need to make proteins, which stops them from multiplying and allows the body's immune system to clear the infection. The ointment is indicated for the topical treatment of impetigo due to susceptible isolates of Staphylococcus aureus and Streptococcus pyogenes.^[4] A separate nasal formulation is used to reduce staphylococcal carriage in the nose.^[3]

Which conditions is mupirocin used or studied for?

• Impetigo — a contagious skin infection that mainly affects children, caused by Staphylococcus aureus or Streptococcus pyogenes. The authorised Phase 3 trial treats 464 children with topical mupirocin for this condition.^[1]
• Staphylococcus aureus nasal carriage — a condition in which the bacterium lives in the nasal cavity without necessarily causing symptoms, but can lead to infection or spread to others. A Phase 3 trial studied mupirocin for this indication but was withdrawn.^[2]

How is mupirocin given?

Mupirocin is applied to the skin as a gel or ointment, and a separate formulation is available for use inside the nose.^[1] The ointment contains 20 mg of mupirocin per gram and is supplied in 15-gram, 22-gram and 30-gram tubes.^[4] The product information states that a small amount is applied to the affected area three times daily for 10 days, using a cotton swab or gauze pad.^[4] Mupirocin ointment is for topical use only and is not intended for intranasal, ophthalmic or other mucosal use; the nasal ointment is a separate product.^[4] The NHS formulary lists mupirocin 2% in white soft paraffin as Bactroban Nasal for nasal staphylococci.^[3]

What do the clinical trials show?

The EU Clinical Trials Information System lists two Phase 3 trials involving mupirocin. In one of them, mupirocin is the test substance; in the other, it is the comparator.^[1]

Which conditions are studied in these trials?

The active trial investigates impetigo in a paediatric population, while the withdrawn trial was designed for adults with chronic active Staphylococcus aureus mono-infection or asymptomatic carriage in the nasal cavity.^[1][2]

What phases and status do these trials have?

Both trials are Phase 3 studies, the latest stage of testing before a medicine is widely used. The impetigo trial is authorised, meaning it is approved to run, while the nasal carriage trial was withdrawn.^[1][2]

What are the trials measuring?

The impetigo trial measures clinical cure at the end of follow-up, defined as the proportion of participants with clinical cure based on the Skin Infection Rating Scale (SIRS) as assessed by a blinded assessor.^[1] The trial is designed to show that Impetine Gel applied twice daily is not inferior to Bactroban Ointment applied three times daily — a non-inferiority design with dose optimisation.^[1] The withdrawn nasal carriage trial was designed to measure the efficacy of 1,8-cineole in monotherapy and in combination with mupirocin, by microbiological analysis of nasal cultures immediately after 7 days of therapy.^[2]

Who can take part in these trials?

The impetigo trial enrols 464 participants from the paediatric population.^[1] The withdrawn nasal carriage trial had planned to enrol 300 adults with chronic active Staphylococcus aureus mono-infection or asymptomatic carriage in the nasal cavity.^[2]

What side effects are known?

The most frequent adverse reactions reported with mupirocin ointment, occurring in at least 1% of patients, are burning, stinging or pain at the application site.^[4] Severe allergic reactions, including anaphylaxis, urticaria, angioedema and generalised rash, have been reported in patients treated with mupirocin formulations.^[4] Other warnings include eye irritation on contact, local irritation, Clostridium difficile-associated diarrhoea, and the potential for overgrowth of nonsusceptible microorganisms, including fungi, with prolonged use.^[4] Mupirocin ointment should not be used on mucosal surfaces, at intravenous sites, or where large quantities of polyethylene glycol could be absorbed, particularly in patients with moderate or severe renal impairment.^[4]