Mechanism Of Action
Mupirocin is an RNA synthetase inhibitor antibacterial [see
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
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)
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.