Introduction
Mupirocin is a naturally occurring antibacterial agent produced by fermentation of Pseudomonas fluorescens. It has a unique mechanism of action by inhibiting bacterial isoleucyl-tRNA synthetase, which blocks protein synthesis and reduces the likelihood of cross-resistance with other antibiotics. Mupirocin has activity against many gram-positive bacteria and some gram-negative bacteria. Due to extensive systemic metabolism, it is available only as topical formulations and is used mainly for treating impetigo, infected skin lesions, and nasal decolonization of Staphylococcus species.
Uses
Mupirocin is an antibacterial ointment used to treat impetigo and secondary skin infections caused by Staphylococcus aureus and Streptococcus pyogenes.
Indicated for the treatment of impetigo and secondary skin infections, leading to traumatic skin lesions, due to Staphylococcus aureus and Streptococcus pyogenes.
Associated Conditions
Pharmacodynamics
Mupirocin is reported to be active against susceptible aerobic gram-positive cocci, such as Staphylococcus aureus, Staphylococcus epidermidis, and other beta-hemolytic streptococciStreptococcus pyogenes. It mediates its antibacterial activity by inhibiting the bacterial protein synthesis and formation of bacterial proteins essential for survival. The minimum bactericidal concentration (MBC) against relevant pathogens is generally eight-fold to thirty-fold higher than the minimum inhibitory concentration (MIC). In one clinical study investigating the therapeutic effectiveness of topical mupirocin in impetigo, the therapeutic response rate was about 94 to 98% after one week following the end of therapy. In clinical studies of patients with primary and secondary skin infections, both elimination of the bacterial pathogen and clinical cure or improvement hav been demonstrated in over 90% of patients receiving topical mupirocin. Mupirocin resistance as high as 81% has been reported previously. Resistance to mupirocin, which occurs more frequently in methicillin-resistant than methicillin-susceptible staphylococci, may occur with the production of a modified isoleucyl-tRNA synthetase, or the acquisition of, by genetic transfer, a plasmid mediating a new isoleucyl-tRNA synthetase.
Mechanism of Action
Mupirocin specifically and reversibly binds to bacterial isoleucyl transfer-RNA (tRNA) synthetase, which is an enzyme that promotes the conversion of isoleucine and tRNA to isoleucyl-tRNA. Inhibition of this enzyme subsequently leads to the inhibition of the bacterial protein and RNA synthesis. Mupirocin is bacteriostatic at lower concentrations but it exerts bactericidal effects with prolonged exposure, killing 90-99% of susceptible bacteria over a 24 hour period.
Absorption
Systemic or percutaneous absorption of mupirocin following dermal application is expected to be minimal in adults and children. Occlusive dressings do not significantly enhance drug absorption, but damaged skin may allow enhanced penetration of the drug across the skin barrier.
Volume of Distribution
No information available.
Protein Binding
The protein binding of mupirocin is reported to be over 95%.
Route of Elimination
Any mupirocin reaching the systemic circulation is rapidly metabolized to form the inactive monic acid, which is eliminated by renal excretion. Following the application of Centany (mupirocin ointment),2% to a 400 cm2 area on the back of 23 healthy volunteers once daily for 7 days, the mean (range) cumulative urinary excretion of monic acid over 24 hrs following the last administration was 1.25% (0.2% to 3.0%) of the administered dose of mupirocin.
Half Life
In healthy male volunteers, the elimination half-life of mupirocin was about 20 to 40 minutes following intravenous administration. The elimination half-life of monic acid was about 30 to 80 minutes.
Clearance
No information available.
Toxicity
LD50 and Nonclinical Toxicity
The oral LD50 value in rats is 5000 mg/kg. Studies evaluating the carcinogenic potential of mupirocin have not been performed. In various in vivo animal and in vitro bacterial assays, there was no evidence of genotoxicity caused by mupirocin. In reproduction studies using male and female rats, there were no signs of impaired fertility upon subcutaneous administration of mupirocin.
Use in special populations
Mupirocin was found to be excreted in human milk. As there is limited data on the use of topical mupirocin in pregnant women, the use of this drug in these patients should be undertaken with caution. Based on the findings in clinical trials, topical mupirocin was shown to be safe and effective in pediatric patients aged 2 months to 16 years.
Food Interactions
No interactions found.
Dosage
Pediatric Use: The safety and effectiveness of Mupirocin have been established in the age range of 2 months to 16 years. Use of the ointment in these age groups is supported by evidence from adequate and well-controlled studies of Mupirocin in impetigo in pediatric patients.
