Mechanism Of Action
Mupirocin is an antibacterial drug [see Microbiology].
Following single or repeated intranasal applications of
0.2 grams of BACTROBAN nasal ointment 3 times daily for 3 days to 5 healthy
adult male subjects, no evidence of systemic absorption of mupirocin was
demonstrated. The dosage regimen used in this trial was for pharmacokinetic
characterization only; see DOSAGE AND ADMINISTRATION for proper clinical
In this trial, the concentrations of mupirocin in urine
and of monic acid in urine and serum were below the limit of determination of
the assay for up to 72 hours after the applications. The lowest levels of
determination of the assay used were 50 ng/mL of mupirocin in urine, 75 ng/mL
of monic acid in urine, and 10 ng/mL of monic acid in serum. Based on the
detectable limit of the urine assay for monic acid, one can extrapolate that a
mean of 3.3% (range: 1.2% to 5.1%) of the applied dose could be systemically
absorbed from the nasal mucosa of adults.
The effect of concurrent application of BACTROBAN nasal
ointment with other intranasal 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.
Pediatrics: The pharmacokinetic properties of mupirocin
following intranasal application of BACTROBAN nasal ointment have not been
adequately characterized in neonates or other children younger than 12 years,
and in addition, the safety and efficacy of the product in children younger
than 12 years have not been established.
Renal Impairment: The pharmacokinetics of
mupirocin have not been studied in individuals with renal insufficiency.
Mupirocin is an antibacterial agent 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 intranasal administration. Mupirocin is highly protein bound ( > 97%),
and the effect of nasal secretions on the minimum inhibitory concentrations
(MICs) of intranasally applied 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
Due to its mode of action, mupirocin does not demonstrate
cross resistance with other classes of antimicrobial agents.
High-level mupirocin resistance ( ≥ 512 mcg/mL) may
be determined using standard disk diffusion or broth microdilution tests1,2.
The significance of these results, with regard to decolonization regimens,
should be evaluated at each medical facility, in conjunction with laboratory,
medical, and infection control staff.
Correlation of BACTROBAN nasal ointment in vitro activity
and MRSA nasal decolonization has been demonstrated in clinical trials [see
All adequate and well-controlled trials of this product
were vehicle-controlled; therefore, no data from direct, head-to-head
comparisons with other products are available. The safety and effectiveness of
applications of this medication for greater than 5 days have not been
established. There are no human clinical or pre-clinical animal data to support
the use of this product in a chronic manner or in manners other than those
described in this prescribing information.
In clinical trials, 210 domestic (US) and 2,130 foreign
adult subjects received BACTROBAN nasal ointment. Greater than 90% of subjects
in clinical trials had eradication of nasal colonization 2 to 4 days after
therapy was completed. Approximately 30% recolonization was reported in 1
domestic trial within 4 weeks after completion of therapy. These eradication
rates were clinically and statistically superior to those reported in subjects
in the vehicle-treated arms of the adequate and well-controlled trials. Those
treated with vehicle had eradication rates of 5% to 30% at 2 to 4 days
post-therapy with 85% to 100% recolonization within 4 weeks.
1. Clinical and Laboratory Standards Institute (CLSI).
Performance Standards for Antimicrobial Susceptibility Testing; 25th Informational
Supplement. CLSI document M100-S22. CLSI, 950 West Valley Rd., Suite 2500,
Wayne, PA 19087, 2015.
2. Patel J, Gorwitz RJ, et al. Mupirocin Resistance. Clinical
Infectious Diseases. 2009; 49(6); 935-41.