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Mechanism Of Action
Mupirocin is an RNA synthetase inhibitor antibacterial [see Microbiology].
Systemic absorption of mupirocin through intact human skin is minimal. The systemic absorption of mupirocin was studied following application of BACTROBAN cream 3 times daily for 5 days to various skin lesions greater than 10 cm in length or 100 cm² in area in 16 adults (aged 29 to 60 years) and 10 children (aged 3 to 12 years). Some systemic absorption was observed as evidenced by the detection of the metabolite, monic acid, in urine. Data from this trial indicated more frequent occurrence of percutaneous absorption in children (90% of subjects) compared with adults (44% of subjects); however, the observed urinary concentrations in children (0.07 to 1.3 mcg per mL [1 pediatric subject had no detectable level]) are within the observed range (0.08 to 10.03 mcg per mL [9 adults had no detectable level]) in the adult population. In general, the degree of percutaneous absorption following multiple dosing appears to be minimal in adults and children.
The effect of the concurrent application of BACTROBAN cream with other topical products has not been studied [see DOSAGE AND ADMINISTRATION].
In a trial conducted in 7 healthy adult male subjects, the elimination half-life after intravenous administration of mupirocin was 20 to 40 minutes for mupirocin and 30 to 80 minutes for monic acid.
Metabolism: Following intravenous or oral administration, mupirocin is rapidly metabolized. The principal metabolite, monic acid, demonstrates no antibacterial activity.
Excretion: Monic acid is predominantly eliminated by renal excretion.
Renal Impairment: The pharmacokinetics of mupirocin have not been studied in individuals with renal insufficiency.
Mupirocin is an RNA synthetase inhibitor antibacterial produced by fermentation using the organism Pseudomonas fluorescens.
Mechanism of Action
Mupirocin inhibits bacterial protein synthesis by reversibly and specifically binding to bacterial isoleucyl-transfer RNA (tRNA) synthetase.
Mupirocin is bactericidal at concentrations achieved by topical administration. Mupirocin is highly protein bound (greater than 97%) and the effect of wound secretions on the minimum inhibitory concentrations (MICs) of mupirocin has not been determined.
Mechanism of Resistance
When mupirocin resistance occurs, it results from the production of a modified isoleucyl-tRNA synthetase, or the acquisition of, by genetic transfer, a plasmid mediating a new isoleucyl-tRNA synthetase. High-level plasmid-mediated resistance (MIC ≥ 512 mcg/mL) has been reported in increasing numbers of isolates of S. aureus and with higher frequency in coagulase-negative staphylococci. Mupirocin resistance occurs with greater frequency in methicillin-resistant than methicillin-susceptible staphylococci.
Due to its mode of action, mupirocin does not demonstrate cross resistance with other classes of antimicrobial agents.
Mupirocin has been shown to be active against susceptible isolates of S. aureus and S. pyogenes, both in vitro and in clinical trials [see INDICATIONS AND USAGE]. The following in vitro data are available, but their clinical significance is unknown. Mupirocin is active against most isolates of Staphylococcus epidermidis.
High-level mupirocin resistance ( ≥ 512 mcg/mL) may be determined using standard disk diffusion or broth microdilution tests.1,2 Because of the occurrence of mupirocin resistance in methicillin-resistant S. aureus (MRSA), it is appropriate to test MRSA populations for mupirocin susceptibility prior to the use of mupirocin using a standardized method.3,4,5
The efficacy of topical BACTROBAN cream for the treatment of secondarily infected traumatic skin lesions (e.g., lacerations, sutured wounds, and abrasions not more than 10 cm in length or 100 cm² in total area) was compared with that of oral cephalexin in 2 randomized, double-blind, double-dummy clinical trials. Clinical efficacy rates at follow-up in the per-protocol populations (adults and pediatric subjects included) were 96.1% for BACTROBAN cream (n = 231) and 93.1% for oral cephalexin (n = 219). Pathogen eradication rates at follow-up in the per-protocol populations were 100% for both BACTROBAN cream and oral cephalexin.
There were 93 pediatric subjects aged 2 weeks to 16 years enrolled per protocol in the secondarily infected skin lesion trials, although only 3 were younger than 2 years of age in the population treated with BACTROBAN cream. Subjects were randomized to either 10 days of topical BACTROBAN cream 3 times daily or 10 days of oral cephalexin (250 mg 4 times daily for subjects greater than 40 kg or 25 mg per kg per day oral suspension in 4 divided doses for subjects less than or equal to 40 kg). Clinical efficacy at follow-up (7 to 12 days post-therapy) in the per-protocol populations was 97.7% (43 of 44) for BACTROBAN cream and 93.9% (46 of 49) for cephalexin.
1. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement. CLSI document M100-S25. Clinical and Laboratory Standards Institute, 950 West Valley Rd., Suite 2500, Wayne, PA 19087, USA, 2015.
2. Patel J, Gorwitz RJ, et al. Mupirocin Resistance. Clinical Infectious Diseases. 2009; 49(6): 935-41.
3. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Tenth Edition. CLSI document M07-A10. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
4. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Twelfth Edition. CLSI document M02-A12. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
5. Finlay JE, Miller LA, Poupard JA. Interpretive criteria for testing susceptibility of staphylococci to mupirocin. Antimicrob Agents Chemother 1997;41(5):1137-1139.
Last reviewed on RxList: 2/11/2016
This monograph has been modified to include the generic and brand name in many instances.
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