ATC Class:D06AX09
VA Class:DE101
Mupirocin is a pseudomonic acid antibiotic produced by Pseudomonas fluorescens .3, 4, 5, 74, 78, 91, 92, 93, 94, 95, 98, 110, 111
Mupirocin 2% ointment for dermatologic use is used for the topical treatment of impetigo caused by Staphylococcus aureus and Streptococcus pyogenes (group A β-hemolytic streptococci; GAS).2, 3, 11, 16, 18, 20, 30, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 56, 77, 79, 83, 91, 92, 93, 94, 95, 100
Although impetigo may be self-limiting, anti-infective treatment is usually indicated to reduce the duration of symptoms and prevent recurrence or transmission to other individuals.2, 14, 15 Empiric treatment with an appropriate narrow-spectrum anti-infective generally is used for initial treatment and is considered reasonable for typical cases.15, 43 Some clinicians suggest in vitro testing (i.e., Gram stain and culture of pus or exudates from the skin lesions) to determine whether the infection is caused by S. aureus and/or β-hemolytic streptococci and confirm in vitro susceptibility of the causative organism,2, 43, 110, 292 especially if impetigo is extensive and/or failed to respond to initial empiric treatment.2, 110 Nonbullous and bullous impetigo have been treated using topical and/or systemic anti-infective therapy.2, 14, 15, 43, 110 Although comparative efficacy of various regimens has not been established in well-controlled clinical trials,2, 14 topical anti-infectives generally are used for less extensive disease and systemic anti-infectives generally are recommended if impetigo is severe or involves numerous lesions2, 14, 15, 43, 100, 110, 292 or if an outbreak of impetigo is affecting multiple individuals (e.g., family members, childcare groups, athletic teams).43, 292 When impetigo is treated empirically, an appropriate narrow-spectrum anti-infective should be selected based on local patterns of resistance reported for S. aureus and S. pyogenes .2, 14, 15, 292
Efficacy of mupirocin 2% ointment for the topical treatment of impetigo was evaluated in a placebo-controlled study in adults and pediatric patients 2 months of age or older.92, 93, 94, 95 Patients were randomized to receive topical mupirocin 2% ointment (formulated in a polyethylene glycol [PEG] vehicle) or topical vehicle placebo applied to affected areas 3 times daily for 8-12 days.92, 93, 94, 95 The clinical efficacy rate at the end of treatment in the evaluable population (adults and pediatric patients) was 71% in those treated with mupirocin ointment and 35% in those treated with vehicle placebo.92, 93, 94, 95 In the evaluable pediatric patients 2 months to 15 years of age, the clinical efficacy rate was 78% in those treated with mupirocin ointment and 36% in those treated with vehicle placebo.92, 93, 94, 95 The pathogen eradication rate in the evaluable population (adults and pediatric patients) was 94 or 62% in those treated with mupirocin ointment or vehicle placebo, respectively.92, 93, 94, 95
In a randomized, unblinded trial in 57 patients with impetigo (55 pediatric patients 7 months of age or older and 2 adults), efficacy of topical treatment with mupirocin 2% ointment formulated in a PEG vehicle applied to affected areas 3 times daily for 8 days was compared with that of oral erythromycin ethylsuccinate (30 or 40 mg/kg daily for 8 days).92, 93, 94, 95 The clinical efficacy rate at the follow-up visit (1 week after treatment completion) in the evaluable population (adults and pediatric patients) was 93% in those treated with mupirocin ointment and 78.5% in those treated with oral erythromycin ethylsuccinate.92, 93, 94, 95 The pathogen eradication rate in the evaluable population was 100% in both treatment groups.92, 93, 94, 95
The comparative efficacy of mupirocin 2% ointment formulated without PEG (Centany®) and mupirocin 2% ointment formulated with PEG for the topical treatment of impetigo was evaluated in a study that included 475 adults and pediatric patients 2 months of age or older who were randomized to receive one of these formulations applied to lesions 3 times daily for 7 days.91 The clinical efficacy rate at the follow-up visit (1 week after treatment completion) in evaluable patients (adults and pediatric patients) was 94 or 95% in those treated with the ointment formulated without or with PEG, respectively.91 In the evaluable pediatric patients 2 months to 15 years of age, the clinical efficacy rate was 93% in those treated with the ointment formulated without PEG and 95% in those treated with the ointment formulated with PEG.91 The pathogen eradication rate at follow-up was the same (98%) with both mupirocin ointment formulations.91
Mupirocin calcium cream for dermatologic use containing 2% mupirocin is used for the topical treatment of secondarily infected traumatic skin lesions (e.g., lacerations, sutured wounds, abrasions) caused by susceptible S. aureus and S. pyogenes .78, 98
Mupirocin has been used for the topical treatment of other primary or secondary superficial skin infections, including ecthyma†, 30, 54, 69 eczema†, 3, 11, 20, 25, 36, 38, 39, 40, 44, 47, 56, 69, 76, 79, 80, 110 folliculitis†, 3, 11, 20, 30, 46, 47, 56, 69, 80, 110 furunculosis†, 30, 44, 54, 56, 69, 80 atopic dermatitis†, 37, 69, 72 epidermolysis bullosa†, 29, 35, 39, 56 and minor wounds†, 3, 20, 38, 39, 46, 54, 56 burns†, 39, 40, 56, 110 and ulcers†.20, 35, 38, 39, 44, 46, 47, 56, 110
Although it has been suggested that topical mupirocin may be effective for the treatment of minor primary or secondary superficial skin infections caused by susceptible bacteria and has the advantage of being associated with fewer adverse effects than systemic anti-infective therapy,3, 40, 41, 45, 70, 79 experts state that an appropriate oral or parenteral anti-infective should be used for the treatment of most purulent skin and skin structure infections (e.g., abscesses, cellulitis, ecthyma, erysipelas, carbuncles, furuncles, wound infections).43, 70, 110, 292
Mupirocin should not be applied topically to surgical wounds in an attempt to prevent surgical site infections.111
Efficacy of mupirocin calcium cream (2% mupirocin) for the topical treatment of secondarily infected traumatic skin lesions (e.g., lacerations, sutured wounds, abrasions) no 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 in adults and pediatric patients (including 3 patients younger than 2 years of age).78, 98 Patients were randomized to receive a 10-day regimen of topical mupirocin calcium cream applied to affected areas 3 times daily or oral cephalexin (250 mg 4 times daily in those weighing more than 40 kg or 25 mg/kg daily given in 4 divided doses in those weighing 40 kg or less).78, 98 The clinical efficacy rate at follow-up in the per-protocol population (adults and pediatric patients) was 96% in those treated with topical mupirocin calcium cream and 93% in those treated with oral cephalexin.78, 98 In the pediatric patients, the clinical efficacy rate at follow-up (7-10 days after treatment) in the per-protocol population was 98% in those treated with topical mupirocin calcium cream and 94% in those treated with oral cephalexin.78, 98 The pathogen eradication rate at follow-up in the per-protocol population (adults and pediatric patients) was 100% for both the mupirocin calcium cream and the oral cephalexin group.78, 98
Although the comparative efficacy of topical mupirocin and oral anti-infectives (e.g., erythromycin, cephalexin, cloxacillin [no longer commercially available in the US]) for the treatment of superficial skin infections has been evaluated in some clinical studies,3, 4, 40, 41, 42, 44, 45, 46, 47, 49, 50, 77, 79, 83 most studies were not blinded and some were poorly controlled in terms of the severity of infection.3, 40, 41, 42, 44, 45, 46, 49, 50, 77, 83, 92
Nasal Carriage of Staphylococcus aureus
Mupirocin calcium ointment for intranasal use containing 2% mupirocin is used intranasally to temporarily eliminate nasal carriage of methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA).3, 4, 15, 16, 32, 33, 34, 52, 55, 61, 62, 63, 74, 80, 81, 82, 85, 86, 88, 105, 106, 107, 108, 109, 111 The ointment also has been used intranasally to temporarily eliminate nasal carriage of methicillin-susceptible S. aureus † (MSSA).3, 4, 15, 16, 32, 34, 80, 81, 85, 86, 88, 105, 106
Mupirocin calcium ointment for intranasal use containing 2% mupirocin is labeled by FDA for eradication of MRSA nasal colonization in adults and children 12 years of age and older and for use in health-care workers as part of a comprehensive infection control program to reduce the risk of infection among patients at high risk of MRSA infection during institutional outbreaks of infections caused by this pathogen.74 The manufacturer states that data are insufficient to establish whether the intranasal ointment is safe and effective when used as part of an intervention program to prevent autoinfection of high-risk patients from their own nasal colonization with S. aureus and that data are insufficient to recommend use of the ointment for general prophylaxis of any infection in any patient population.74
Because nasal carriage of S. aureus is considered a risk factor for subsequent staphylococcal infections, intranasal mupirocin has been used to eliminate nasal carriage of S. aureus in carriers at high-risk of staphylococcal infections (e.g., surgical patients, cancer patients, dialysis patients, patients in intensive care units or long-term care settings) in an attempt to decrease the incidence of infections in these patients†.15, 81, 85, 86, 89, 90, 105, 106, 107, 108, 109, 110, 111, 360, 374 For preoperative decolonization† in patients identified as nasal carriers of MRSA or MSSA, intranasal mupirocin has been used with or without a topical agent (e.g., whole-body disinfection with chlorhexidine gluconate skin cleanser, oral cleansing with chlorhexidine gluconate oral rinse)15, 105, 106, 107, 108, 109, 110, 111, 360, 374 and such decolonization regimens have been used as an adjunct to usual perioperative prophylaxis with systemic anti-infectives in certain surgical patients.374
Intranasal mupirocin also has been used to eradicate nasal carriage of MRSA and/or MSSA in neonates and infants† in neonatal intensive care units (NICUs).113, 114, 115, 116, 117 Intranasal mupirocin has been included in various decolonization regimens in such neonates and infants in an attempt to reduce the rate of S. aureus transmission and rate of clinical infection in this patient population.113, 114, 115, 116, 117
Use of intranasal mupirocin in high-risk patients remains controversial because data are limited or conflicting regarding the potential benefits and risks of intranasal mupirocin decolonization regimens and because of concerns about emergence of mupirocin resistance in staphylococci.15, 101, 104, 105, 107, 108, 109, 110, 374 Some experts suggest that eradication of nasal carriage of S. aureus may be a reasonable strategy in certain patients with multiple documented recurrences of MRSA infection81, 85, 108 and there is some evidence from controlled studies that use of intranasal mupirocin in S. aureus carriers can reduce the overall S. aureus infection rate in high-risk patients.81, 85, 86, 105, 108, 109, 110 There also is some evidence that a preoperative decolonization regimen of intranasal mupirocin (with or without a topical agent) in nasal carriers of S. aureus may decrease the risk of surgical site infections following certain procedures (e.g., cardiothoracic surgery, neurosurgery, orthopedic surgery)105, 107, 108, 110, 360, 374 and that use of such decolonization regimens may decrease the risk of S. aureus infections in hemodialysis and peritoneal dialysis patients.90, 105, 108 However, some experts state that data are insufficient to support routine use of anti-infectives for eradication of S. aureus colonization15, 81, 82, 85, 86, 101, 105, 374 and that a targeted decolonization strategy in selected patients based on screening and risk assessment is preferred over unrestricted use of decolonization regimens.15, 101, 105, 106, 107, 108, 110, 374
Permanent eradication of nasal carriage of S. aureus following intranasal or systemic anti-infective therapy is unlikely;3, 16, 33, 62, 63 recolonization generally occurs in 30-100% of patients regardless of the anti-infective agent or regimen used.3, 32, 33, 74, 113, 117 Studies using intranasal mupirocin indicate that nasal carriage of S. aureus usually is eliminated within the first 1-4 days of intranasal treatment.3, 4, 16, 32, 33, 34, 61, 74, 80, 111 The eradication rate in S. aureus carriers measured shortly after completion of a 5-day regimen of intranasal mupirocin may be 80% or higher;74, 105, 111, 113 however, recolonization often occurs as soon as 2-17 days16, 32, 33, 34, 80 or up to several weeks or months after treatment with intranasal mupirocin.4, 16, 32, 61, 74, 111 Recolonization may be due to the same S. aureus strain or a new strain.111
Mupirocin is applied topically to the skin as an ointment for dermatologic use containing 2% mupirocin in a water-miscible vehicle containing polyethylene glycol (PEG) (generic)92, 93, 94, 95 or as an ointment for dermatologic use containing 2% mupirocin in a vehicle without PEG (Centany®).91
Mupirocin calcium is applied topically to the skin as a cream for dermatologic use containing 2% mupirocin in an oil and water-based vehicle (Bactroban®, generic).78, 98
Mupirocin ointment for dermatologic use and mupirocin calcium cream for dermatologic use are for external use only and should not be applied to eyes or mucous membranes and should not be administered intranasally.78, 91, 92, 93, 94, 95, 98 (See Precautions Related to Topical Administration under Cautions: Precautions and Contraindications.)
A small amount of the topical ointment or cream should be applied to the affected area78, 91, 92, 93, 94, 95, 98 using a cotton swab or gauze pad.78, 92, 93, 94, 95, 98
Treated areas of skin may be covered with a sterile gauze dressing, if desired.78, 91, 92, 93, 94, 95, 98
Hands should be washed before and after applying topical mupirocin ointment or mupirocin calcium cream, unless the hands are being treated.78, 92, 93, 94, 95, 98
Mupirocin ointment or mupirocin calcium cream for dermatologic use should not be applied concurrently with any other lotions, creams, or ointments.78, 92, 93, 94, 95, 98
Mupirocin calcium is applied intranasally as an ointment specifically formulated for intranasal administration (Bactroban® nasal ointment).74 This intranasal formulation contains 2% mupirocin in a soft white ointment vehicle of paraffin and a mixture of glycerin esters (Softisan® 649).74
Mupirocin nasal ointment is for intranasal use only and contact with the eyes should be avoided.74 (See Precautions Related to Intranasal Administration under Cautions: Precautions and Contraindications.)
Mupirocin ointment for intranasal use is commercially available in single-use tubes.74 The ointment is administered by placing one-half (approximately 0.25 g) of the ointment contained in a single-dose tube into each nostril.74 The ointment should then be distributed evenly throughout the nares by pressing together and releasing the sides of the nose repetitively for approximately 1 minute.74 The single-use tube should be discarded after application and should not be reused.74
Hands should be washed before and after applying mupirocin calcium ointment for intranasal use.74
Mupirocin intranasal ointment should not be applied concurrently with other intranasal preparations.74
Although commercially available mupirocin ointment for dermatologic use has been used intranasally†, 3, 33, 52, 85 the manufacturers and some clinicians state that the commercially available mupirocin ointments for dermatologic use (formulated with or without PEG) should not be substituted since these ointments should not be used intranasally.3, 16, 18, 51, 52, 66, 70, 91, 92, 93, 94, 95 (See Intranasal Administration under Cautions: Adverse Effects.)
For the topical treatment of impetigo caused by Staphylococcus aureus and Streptococcus pyogenes (group A β-hemolytic streptococci; GAS) in pediatric patients 2 months of age or older, a small amount of mupirocin 2% ointment for dermatologic use should be applied to the affected area 3 times daily.91, 92, 93, 94, 95
The manufacturers state that mupirocin 2% ointment for dermatologic use may be used for up to 10 days for the topical treatment of impetigo.92, 93, 94, 95 Mupirocin 2% ointment has been administered for a duration of 3-14 days for the topical treatment of impetigo.2, 14, 43, 48, 83, 111
If there is no clinical response within 3-5 days, the patient should be reevaluated.91, 92, 93, 94, 95
For the topical treatment of secondarily infected traumatic skin lesions (up to 10 cm in length or 100 cm2 in total area) in pediatric patients 3 months of age or older, a small amount of mupirocin calcium cream for dermatologic use containing 2% mupirocin should be applied to the affected area 3 times daily for 10 days.78, 98
If there is no clinical response within 3-5 days, the patient should be reevaluated.78, 98
Nasal Carriage of Staphylococcus aureus
When mupirocin calcium ointment for intranasal use containing 2% mupirocin is used to eliminate nasal carriage of methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA) in children 12 years of age or older, one-half (approximately 0.25 g) of the ointment contained in the single-dose tube should be applied into each nostril twice daily (morning and evening) for 5 days.74 (See Intranasal Administration under Dosage and Administration: Administration.)
The manufacturer states that safety and efficacy of more than 5 days of treatment with mupirocin intranasal ointment have not been established.74
For the topical treatment of impetigo caused by S. aureus and S. pyogenes (group A β-hemolytic streptococci; GAS) in adults, a small amount of mupirocin 2% ointment for dermatologic use should be applied to the affected area 3 times daily.91, 92, 93, 94, 95
The manufacturers state that mupirocin 2% ointment for dermatologic use may be used for up to 10 days for the topical treatment of impetigo.92, 93, 94, 95 Mupirocin 2% ointment has been administered for a duration of 3-14 days for the topical treatment of impetigo.2, 14, 43, 48, 83, 111
If there is no clinical response within 3-5 days, the patient should be reevaluated.91, 92, 93, 94, 95
For the treatment of secondarily infected traumatic skin lesions (up to 10 cm in length or 100 cm2 in total area) in adults, a small amount of mupirocin calcium cream for dermatologic use containing 2% mupirocin should be applied to the affected area 3 times daily for 10 days.78, 98
If there is no clinical response within 3-5 days, the patient should be reevaluated.78, 98
Nasal Carriage of Staphylococcus aureus
When mupirocin calcium ointment for intranasal use containing 2% mupirocin is used to eliminate nasal carriage of MRSA in adults, one-half (approximately 0.25 g) of the ointment contained in the single-dose tube should be applied into each nostril twice daily (morning and evening) for 5 days.74 (See Intranasal Administration under Dosage and Administration: Administration.)
The manufacturer states that safety and efficacy of more than 5 days of treatment with mupirocin intranasal ointment have not been established.74
Mupirocin generally is well tolerated when applied topically to skin.3, 4, 20, 35, 39, 57, 79 Most adverse effects of topical mupirocin are mild, transient,56 local reactions3, 4, 39 that require discontinuance4, 30, 36, 54, 56, 57 of the drug in less than 1% of patients.4
Following topical application of mupirocin ointment or mupirocin calcium cream to skin, burning,3, 7, 20, 30, 35, 36, 39, 46, 54, 56, 78, 92, 93, 94, 95, 98 stinging,3, 4, 35, 36, 52, 92, 93, 94, 95 pain,3, 4, 7, 52, 56, 92, 93, 94, 95 pruritus,3, 4, 7, 20, 36, 39, 41, 52, 54, 56, 78, 91, 92, 93, 94, 95, 98 and rash3, 4, 20, 57, 78, 91, 92, 93, 94, 95, 98 have occurred in less than 1-4% of patients.3, 4, 39, 78, 98 In addition, erythema,56, 92, 93, 94, 95 dry skin,52, 56, 78, 92, 93, 94, 95, 98 tenderness,92, 93, 94, 95 cellulitis,78, 98 pain or bleeding secondary to eczema,78, 98 secondary wound infection,78, 98 swelling,92, 93, 94, 95 increased exudate,92, 93, 94, 95 contact dermatitis,91, 92, 93, 94, 95 furunculosis,91 and exfoliative dermatitis91 have occurred in less than 1% of patients.91, 92, 93, 94, 95
Mupirocin appears to have minimal potential for inducing allergic contact sensitization following topical application.7, 9, 56, 57, 110 In addition, the drug only has weak ultraviolet light-absorbing properties and is unlikely to cause phototoxicity or photoallergic dermatitis.3, 4, 5, 9, 16, 80 Initial controlled studies in healthy individuals did not reveal evidence of local irritation,3, 4, 6, 7, 9, 80 contact sensitization,3, 6, 7, 9, 20, 80 phototoxicity,9, 80 or photoallergic dermatitis3, 9, 80 following topical application of mupirocin to intact3, 4, 7, 20 or irritated9, 20 skin (with or without an occlusive dressing).3, 4 However, although a causal relationship to the drug has not been definitely established,26, 45, 46, 79 allergic contact dermatitis or dermatitis has been reported rarely in patients receiving topical mupirocin.26, 45, 46, 78, 79, 91, 92, 93, 94, 95, 110
Systemic reactions have been reported rarely following topical application of mupirocin or mupirocin calcium to skin.38, 56, 78, 98 Nausea has been reported in 1-5%38, 56, 78, 92, 93, 94, 95 and headache has been reported in 2-4% of patients.78, 98 Other systemic effects reported in less than 1% of patients receiving topical mupirocin include dizziness,78, 98 abdominal pain,78, 98 and ulcerative stomatitis.78, 98
Systemic allergic reactions, including anaphylaxis, urticaria, angioedema, and generalized rash, have been reported in patients receiving mupirocin ointment for dermatologic use or mupirocin calcium cream for dermatologic use.78, 91, 92, 93, 94, 95, 98
Some preparations of mupirocin ointment for dermatologic use contain the drug in a polyethylene glycol (PEG) vehicle.92, 93, 94, 95 It has been suggested that some of the adverse local effects reported with topical mupirocin ointment may be related to the PEG vehicle rather than the drug itself since controlled studies indicate the incidence of some of these adverse effects is similar when the PEG vehicle is used topically alone.3, 4, 26, 39, 45, 46, 79 In addition to its potential to cause local effects, PEG can be absorbed percutaneously into systemic circulation following topical application to open wounds or damaged skin and then is excreted by the kidneys.66, 67, 68, 71, 92, 93, 94, 95 Prolonged or repeated application of a PEG-containing ointment to open wounds or large areas of damaged skin (e.g., burns) may result in systemic absorption66, 67, 68, 71, 92, 93, 94, 95 of potentially toxic amounts of PEG.66, 67, 68, 71 Rarely, renal failure and death have been associated with topical application of PEG-containing ointments in burn patients and in animal burn models.66, 67, 68, 71
Following intranasal application of commercially available mupirocin calcium ointment for intranasal use (mupirocin calcium in a soft ointment base formulated with paraffin and a mixture of glycerin esters [Softisan® 649]), the most frequently reported adverse effects are headache (9%),74 rhinitis (6%),74 respiratory disorders (including upper respiratory tract congestion) (5%),74 pharyngitis (4%),74 taste perversion (3%),74 and cough (2%).74 Local effects, including burning/stinging and pruritus, also have been reported in 1-2% of patients.74 Other systemic effects reported in less than 1% of patients receiving the intranasal mupirocin preparation include blepharitis,74 diarrhea,74 dry mouth,74 ear pain,74 epistaxis,74 nausea,74 and rash.74
Systemic allergic reactions, including anaphylaxis, urticaria, angioedema, and generalized rash, have been reported during postmarketing experience in patients receiving topical mupirocin, including mupirocin ointment for intranasal use.74
Although mupirocin ointment for dermatologic use in a PEG vehicle has sometimes been used intranasally†, 3, 16, 18, 51, 52, 105 intranasal application of the ointment for dermatologic use has caused irritation of the nasal mucosa3, 16, 18, 51, 52 and local stinging,92, 93, 94, 95 soreness, drying,92, 93, 94, 95 and pruritus.52 These local effects may have been caused by the PEG vehicle.3, 16, 18, 51, 52 The manufacturers and some clinicians state that mupirocin ointments for dermatologic use (formulated with or without PEG) should not be used intranasally.3, 16, 18, 51, 52, 66, 70, 91, 92, 93, 94, 95
Precautions and Contraindications
Mupirocin is contraindicated in patients with a history of hypersensitivity to the drug or any ingredient in the formulation.74, 78, 91, 92, 93, 94, 95, 98
If sensitization or severe local irritation occurs or if manifestations suggesting a systemic allergic reaction (e.g., anaphylaxis, urticaria, angioedema, rash, wheezing, or swelling of lips, face, or tongue) occur, mupirocin should be discontinued and appropriate alternative anti-infective therapy substituted.74, 78, 91, 92, 93, 94, 95, 98
Superinfection/Clostridium difficile-associated Diarrhea and Colitis
As with other anti-infectives, prolonged use of mupirocin may result in overgrowth of nonsusceptible organisms, including fungi.74, 78, 91, 92, 93, 94, 95, 98 If superinfection occurs, mupirocin should be discontinued and appropriate therapy instituted.74
Treatment with anti-infectives alters the normal colon flora and may permit overgrowth of Clostridium difficile .74, 78, 91, 92, 93, 94, 95, 98, 302, 303, 304 C. difficile infection (CDI) and C. difficile -associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives and may range in severity from mild diarrhea to fatal colitis.74, 78, 91, 92, 93, 94, 95, 98, 302, 303, 304 C. difficile produces toxins A and B, which contribute to the development of CDAD;74, 78, 91, 92, 93, 94, 95, 98, 302, 303, 304 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.74, 78, 91, 92, 93, 94, 95, 98
CDAD should be considered in the differential diagnosis in patients who develop diarrhea during or after anti-infective therapy.74, 78, 91, 92, 93, 94, 95, 98, 302, 303, 304 Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.74, 78, 91, 92, 93, 94, 95, 98
If CDAD is suspected or confirmed, anti-infectives not directed against C. difficile should be discontinued whenever possible.74, 78, 91, 92, 93, 94, 95, 98, 302, 303, 304 Patients should be managed with appropriate anti-infective therapy directed against C. difficile (e.g., vancomycin, fidaxomicin, metronidazole), appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), and surgical evaluation as clinically indicated.74, 78, 91, 92, 93, 94, 95, 98, 302, 303, 304
Precautions Related to Topical Administration
Mupirocin ointment for dermatologic use and mupirocin calcium cream for dermatologic use are intended for topical application to the skin only and should not be applied to eyes or mucous membranes (including intranasal mucous membranes).78, 91, 92, 93, 94, 95, 98 (See Intranasal Administration under Cautions: Adverse Effects.)
Patients should be advised that if mupirocin ointment or mupirocin calcium cream comes into contact with the eyes, the eyes should be thoroughly rinsed with water.78, 91, 92, 93, 94, 95, 98
Clinicians should consider that clinically important amounts of PEG could be absorbed if a preparation containing PEG is used in patients with extensive open wounds or burns and that toxicity is possible.66, 67, 68, 71 The manufacturers state that preparations of mupirocin ointment for dermatologic use formulated in a PEG vehicle should not be used in conditions where absorption of large quantities of PEG is possible, especially if there is evidence that the patient has moderate or severe renal impairment.92, 93, 94, 95
Mupirocin ointment for dermatologic use should not be used with IV cannulae or at central IV sites because of the potential to promote fungal infections and anti-infective resistance.92, 93, 94, 95
Patients receiving mupirocin ointment or mupirocin calcium cream for dermatologic use should be advised to contact a clinician if there is no evidence of improvement 3-5 days after the drug is initiated.78, 91, 92, 93, 94, 95, 98
Patients also should be advised to contact a clinician if signs of a local adverse reaction (e.g., irritation, severe itching, rash) occur.78, 91, 92, 93, 94, 95, 98 In addition, patients should be instructed to discontinue topical mupirocin therapy and immediately seek emergency care if a severe allergic reaction (e.g., wheezing or swelling of the lips, face, or tongue) occurs.78, 92, 93, 94, 95, 98
Precautions Related to Intranasal Administration
Mupirocin calcium ointment for intranasal use is intended only for topical intranasal application to mucous membranes of the nose and should not be applied to eyes.74 When this ointment was applied to the eye under testing conditions, severe symptoms such as burning and tearing occurred; symptoms resolved within days to weeks after the drug was discontinued.74 Patients should be advised that if mupirocin ointment for intranasal use gets in or near the eyes, the eyes should be thoroughly rinsed with water.74
Patients should be advised of the importance of completing the full course of treatment with mupirocin ointment for intranasal use.74
Patients should be advised to discontinue the intranasal ointment and notify a clinician if any signs of local adverse reactions (e.g., irritation, severe itching, rash) occur.74 In addition, patients should be advised to immediately seek emergency care if a severe allergic reaction (e.g., wheezing or swelling of the lips, face, or tongue) occurs.74
Selection and Use of Anti-infectives
Staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA), with high-level resistance to mupirocin have been reported74, 78, 92, 93, 94, 95, 98, 101, 102, 103, 104, 105, 110, 111 and have been associated with treatment failure (see Resistance).102, 103, 105, 110, 111
Appropriate in vitro testing using standardized procedures to detect high-level mupirocin resistance in staphylococci and evaluate local patterns of resistance may be indicated prior to use of mupirocin.78, 92, 93, 94, 95, 98 The clinical importance of results of resistance testing with regard to nasal decolonization regimens should be evaluated at each medical facility in conjunction with laboratory, medical, and infection control staff.74
Mupirocin ointment for dermatologic use: Safety and efficacy have not been established in children younger than 2 months of age.91, 92, 93, 94, 95 Use of the topical ointment in children 2 months to 16 years of age is supported by evidence from adequate and well-controlled studies in adults and children with impetigo.91, 92, 93, 94, 95
Mupirocin calcium cream for dermatologic use: Safety and efficacy have not been established in children younger than 3 months of age.78, 98 Use of the topical cream in children 3 months to 16 years of age is supported by evidence from adequate and well-controlled studies in adults and additional data from pediatric patients included in the adult studies.78, 98
Mupirocin calcium ointment for intranasal use: Safety and efficacy have not been established in children younger than 12 years of age.74 There is some evidence that substantial systemic absorption of mupirocin can occur following topical intranasal application of the ointment in neonates and premature infants.74 (See Intranasal Administration under Pharmacokinetics: Absorption.)
In 2 well-controlled studies of mupirocin calcium cream for dermatologic use that included geriatric patients older than 65 years of age, there were no overall differences in efficacy and safety of the drug in this age group compared with younger adults.78, 98
Mutagenicity and Carcinogenicity
Mupirocin was not mutagenic in various in vitro and in vivo tests, including rat primary hepatocyte unscheduled DNA synthesis test, sediment analysis for DNA strand breaks, Salmonella reversion test (Ames test), Escherichia coli mutation assay, human lymphocyte metaphase test, mouse lymphoma assay, and mouse bone marrow micronuclei assay.74, 78, 91, 92, 93, 94, 95, 98
The carcinogenic potential of mupirocin has not been evaluated to date in long-term animal studies.74, 78, 91, 92, 93, 94, 95, 98
Pregnancy, Fertility, and Lactation
Data are insufficient to determine whether there is a drug-associated risk with use of mupirocin ointment for dermatologic use, mupirocin calcium cream for dermatologic use, or mupirocin calcium ointment for intranasal use in pregnant women.74, 78, 91, 92, 93, 94, 95, 98 One manufacturer states that mupirocin ointment for dermatologic use should be used during pregnancy only if clearly needed.91
Systemic absorption of mupirocin following topical application to intact skin is minimal.78, 92, 93, 94, 95, 98 Although systemic absorption of mupirocin was reported to be negligible following intranasal application of mupirocin calcium ointment for intranasal use in adults, the dosage regimen used in this study did not mimic the recommended intranasal dosage.74
Reproduction studies in rats or rabbits using subcutaneous mupirocin in dosages up to 22 or 43 times, respectively, the usual human topical dosage or up to 65 or 130 times, respectively, the usual human intranasal dosage have not revealed evidence of developmental toxicity.74, 78, 91, 92, 93, 94, 95, 98
Reproduction studies in rats using subcutaneous mupirocin in dosages up to 14 times the usual human topical dosage or 41 times the usual human intranasal dosage have not revealed evidence of impaired fertility or impaired reproductive performance.74, 78, 91, 92, 93, 94, 95, 98
It is not known whether systemically absorbed mupirocin is distributed into human milk, affects milk production, or affects the breast-fed infant.74, 78, 91, 92, 93, 94, 95, 98 Because systemic absorption of mupirocin is minimal following topical application to skin and negligible following intranasal administration, the manufacturers state that mupirocin exposure in breast-feeding infants is unlikely.74, 78, 92, 93, 94, 95, 98
The benefits of breast-feeding and the importance of mupirocin to the woman should be considered along with potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition.74, 78, 92, 93, 94, 95, 98
One manufacturer states that mupirocin ointment for dermatologic use should be used with caution in nursing women.91
If a breast and/or nipple is being treated with mupirocin ointment for dermatologic use or mupirocin calcium cream for dermatologic use, the treated area should be thoroughly washed prior to breast-feeding to minimize oral exposure to the drug in the breast-feeding infant.78, 92, 93, 94, 95, 98
Although the clinical importance has not been determined, in vitro studies using Escherichia coli indicate that chloramphenicol interferes with the antibacterial action of mupirocin on RNA synthesis.3, 19, 23
Concurrent use of mupirocin calcium ointment for intranasal use and other intranasal preparations has not been studied to date.74 The manufacturer states that mupirocin intranasal ointment should not be used concurrently with any other intranasal preparations.74
Data are not available regarding concurrent application to skin of mupirocin ointment for dermatologic use or mupirocin calcium cream for dermatologic use with other topical preparations.78, 91, 92, 93, 94, 95, 98 The manufacturers state that the ointment or cream for dermatologic use should not be applied concurrently with any other topical preparations.78, 92, 93, 94, 95, 98
The LD50 of mupirocin in rats is greater than 5 g/kg following oral or subcutaneous administration and greater than 2.5 g/kg following IV administration.6
Mupirocin is an RNA synthetase inhibitor antibacterial.74, 78, 92, 93, 94, 95, 98 Mupirocin inhibits protein synthesis in susceptible bacteria by reversibly binding to bacterial isoleucine-tRNA ligase (isoleucyl-tRNA synthetase),4, 5, 6, 11, 17, 19, 21, 23, 24, 74, 78, 80, 91, 92, 93, 94, 95, 98, 110 the enzyme that catalyzes the formation of isoleucyl-tRNA from isoleucine and tRNA.5, 16, 80, 110 Mupirocin contains an epoxide side chain that resembles isoleucine and competes with this amino acid for its binding site on bacterial isoleucine-tRNA ligase.5, 19, 21, 24 This interferes with the formation of an enzyme-aminoacyladenylate complex, the first step in the formation of isoleucyl-tRNA, and results in depletion of cellular concentrations of isoleucyl-tRNA and inhibition of bacterial protein and RNA synthesis.5, 16, 24, 27, 80 Studies using isoleucine-tRNA ligase obtained from rat liver indicate that mupirocin also competes with isoleucine for its binding site on the mammalian enzyme,5, 19, 21, 24 but the drug has a much lower affinity for the mammalian enzyme than for the bacterial enzyme.5, 19, 21, 24, 110
In vitro studies indicate that mupirocin has no effect on DNA-directed RNA polymerase, but has a weak inhibitory effect on polyphenylalanine formation in ribosomal preparations from E. coli .19 Mupirocin has only minimal effects on bacterial DNA synthesis and cell wall peptidoglycan synthesis and no effect on bacterial oxidative phosphorylation.19, 23
Mupirocin usually is bacteriostatic in vitro at low concentrations, but may be bactericidal at high concentrations.3, 4, 5, 8, 13, 16, 23, 27, 80, 110 The drug usually is bactericidal at concentrations attained following topical application of mupirocin 2% ointment for dermatologic use or mupirocin calcium cream for dermatologic use containing 2% mupirocin or intranasal application of mupirocin calcium ointment for intranasal use containing 2% mupirocin.3, 4, 5, 8, 13, 23, 74, 78, 91, 92, 93, 94, 95, 98, 110 The minimum bactericidal concentration (MBC) of the drug against Staphylococcus aureus is usually 8-32 times higher than the minimum inhibitory concentration (MIC) of the drug.3, 4, 8, 12, 27, 80, 91 The effect of wound or nasal secretions on mupirocin MICs has not been determined.78, 91, 92, 93, 94, 95, 98
In vitro studies indicate that mupirocin is most active at a slightly acidic, rather than a neutral or alkaline pH.3, 4, 8, 12, 16, 110 The pH of normal skin (about 5.5) presumably contributes to the activity of the drug following topical application to skin.13
Mupirocin has a narrow spectrum of activity.21, 23 The drug is active in vitro against some gram-positive aerobic bacteria78, 91, 92, 93, 94, 95, 98, 110 and some gram-negative aerobic bacteria,3, 8, 11, 12, 56, 80, 91, 93, 94, 95, 98, 110 but is inactive against anaerobic bacteria,3, 4, 8, 12, 80, 110 Chlamydia ,4, 8, 12, 80 and fungi.3, 4, 8, 12, 80, 110
Gram-positive Aerobic Bacteria
Mupirocin is active in vitro against some strains of Staphylococcus aureus ,3, 4, 8, 11, 12, 20, 30, 32, 34, 51, 55, 56, 74, 78, 80, 91, 92, 93, 94, 95, 98 S. epidermidis ,3, 4, 8, 11, 12, 20, 56, 78, 80, 92, 93, 94, 95, 98 and S. saprophyticus .4, 8, 12, 80 The drug is active against some penicillinase-producing,3, 4, 80 nonpenicillinase-producing,3, 4, 80 and methicillin-resistant strains.3, 4, 33, 34, 52, 55, 62, 74, 78, 91, 92, 93, 94, 95 Susceptible methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA) usually are inhibited in vitro by mupirocin concentrations of 0.03-2 mcg/mL, and other susceptible S. aureus are inhibited in vitro by concentrations of 0.04-0.32 mcg/mL.3, 4, 8, 11, 12, 32, 34, 51, 56, 80 Mupirocin may be active in vitro against S. aureus that are resistant to some other anti-infective agents, including penicillins, aminoglycosides, erythromycin, chloramphenicol, fusidic acid, lincomycin, and tetracycline.3, 4, 12, 80, 110
Mupirocin is active in vitro against most Streptococcus pneumoniae ,3, 4, 8, 11, 12, 56, 80 S. pyogenes (group A β-hemolytic streptococci; GAS),3, 4, 8, 12, 56, 78, 80, 91, 92, 93, 94, 95, 98 S. agalactiae (group B streptococci; GBS),3, 4, 8, 12, 80 groups C and G streptococci,4, 8, 12 and viridans streptococci.3, 4, 8, 12 In vitro, these streptococci are inhibited by mupirocin concentrations of 0.12-2 mcg/mL.3, 4, 8, 12, 56, 80 Mupirocin concentrations of 32-64 mcg/mL generally are required in vitro to inhibit nonenterococcal group D streptococci ( S. bovis , S. equinus ).4, 8, 12, 80 Enterococci, including E. faecalis (formerly S. faecalis ), are resistant to the drug.4, 8, 11, 12, 20, 80, 110
Mupirocin is active in vitro against Listeria monocytogenes , and the MIC reported for this organism has been reported to be 8 mcg/mL.3, 4, 8, 12, 80 The MIC reported for Erysipelothrix rhusiopathiae is 2-8 mcg/mL.4, 8, 12, 80 Corynebacterium , including JK strains, generally require mupirocin concentrations of 64 mcg/mL or greater for in vitro inhibition.8, 12, 80
Gram-negative Aerobic Bacteria
Mupirocin is active in vitro against Neisseria gonorrhoeae 3, 4, 8, 12, 56, 80 and N. meningitidis ,4, 8, 12, 80 and the MIC of the drug reported for these organisms is 0.01-0.05 mcg/mL.
Haemophilus influenzae 3, 4, 8, 12, 56, 80 and Moraxella catarrhalis 4, 8, 12, 20, 80 generally are inhibited in vitro by mupirocin concentrations of 0.12-0.2 mcg/mL. Bordetella pertussis and Pasteurella multocida reportedly are inhibited in vitro by mupirocin concentrations of 0.02-0.25 mcg/mL.3, 4, 8, 12, 80
Most Enterobacteriaceae, including Citrobacter , Escherichia coli , Klebsiella pneumoniae , Proteus mirabilis , and P. vulgaris , require in vitro mupirocin concentrations of 64-128 mcg/mL for inhibition and are considered resistant to the drug.8, 12, 20, 56, 80 Morganella morganii and Serratia marcescens require mupirocin concentrations of 1600-6400 mcg/mL for in vitro inhibition.8, 80 Pseudomonas aeruginosa is considered resistant to the drug.8, 11, 12, 20, 56
Cutibacterium acnes (formerly Propionibacterium acnes ),3, 4, 8, 12, 80Clostridium difficile ,3, 4, 8, 12, 80Peptococcus ,4, 12Peptostreptococcus ,4, 12 and Bacteroides fragilis 12 generally require mupirocin concentrations of 32 mcg/mL or greater for in vitro inhibition and are considered resistant to the drug.3, 4, 8, 12, 80
Mupirocin is inactive against fungi, including Trichophyton mentagrophytes ,4, 8, 80 Malassezia ovalis ( Pityrosporum ovale ),4, 8, 80 Candida albicans ,3, 4, 8, 80 Cryptococcus neoformans ,3, 4, 8, 80 and Aspergillus fumigatus .3, 4, 8, 80
Resistance to mupirocin has been produced in vitro in Staphylococcus aureus initially susceptible to the drug;3, 8, 33, 58, 80, 110 resistance in these strains occurred in a slow, stepwise manner and was not reversible.8, 58
S. aureus naturally resistant to mupirocin have been reported and mupirocin-resistant S. aureus , including methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA), have emerged during therapy with the drug.3, 12, 17, 33, 58, 59, 63, 74, 78, 91, 92, 93, 94, 95, 98, 101, 102, 103, 104, 110, 111 Mupirocin resistance has been reported more frequently in methicillin-resistant than in methicillin-susceptible staphylococci,15, 78, 92, 93, 94, 95, 98, 101 and also has been reported in coagulase-negative staphylococci, including S. epidermidis .11, 12, 15, 58, 59, 74, 78, 91, 92, 93, 94, 95, 103 Mupirocin resistance in staphylococci has emerged most frequently in patients who received the drug for prolonged periods,105, 110, 111 but also has been reported with short-term mupirocin treatment.110, 111
Staphylococcal isolates with low- or intermediate-level mupirocin resistance are usually defined as those with MICs of 8-256 mcg/mL and those with high-level mupirocin resistance are defined as those with MICs of 512 mcg/mL or greater.91, 92, 93, 94, 95, 98, 101, 103, 110, 111 The clinical importance of naturally occurring staphylococci with low-level resistance to mupirocin is unclear because of the high concentration of mupirocin (20 mg/mL) in commercially available preparations of the drug for dermatologic or intranasal use.105, 110, 111 Treatment failures (e.g., failure of intranasal mupirocin to eliminate nasal carriage of MRSA) have been reported when staphylococci with high-level mupirocin resistance were involved.102, 103, 105, 110, 111 High-level resistance to mupirocin has been reported in increasing numbers of S. aureus isolates and with higher frequency in coagulase-negative staphylococci.74, 78, 91, 92, 93, 94, 95, 98, 101
Mupirocin resistance can result from mutational changes within native bacterial isoleucine-tRNA ligase (isoleucyl-tRNA synthetase), the target enzyme of mupirocin, or may be mediated by transferable plasmids that code for a new modified isoleucyl-tRNA synthetase.15, 58, 74, 78, 91, 92, 93, 94, 95, 98, 101, 103, 110, 111 A plasmid-mediated mupA gene has been reported in the majority of strains with high-level mupirocin resistance;15, 101, 103, 110, 111 however, a plasmid-mediated mupB gene also has been identified and has been associated with high-level mupirocin resistance.15, 101, 110, 111, 112
Pseudomonas fluorescens , the organism that produces mupirocin, is resistant to the drug.5, 21, 24, 27 This apparently occurs because isoleucyl-tRNA synthetase is structurally different in this organism and has a low affinity for mupirocin.21, 91 It is not known whether factors that affect permeability of Ps. fluorescens also contribute to resistance to the drug.21
Mupirocin, because of its unique mechanism of action, has a low potential for cross-resistance with other classes of anti-infectives.74, 78, 91, 92, 93, 94, 95, 98, 110 In initial studies, there was no evidence of cross-resistance with chloramphenicol, erythromycin, fusidic acid, gentamicin, lincomycin, methicillin (no longer commercially available in the US), neomycin, novobiocin (no longer commercially available in the US), penicillin, streptomycin, or tetracycline.3, 8, 12, 17, 80 Rarely, mupirocin-resistant strains of S. aureus have been found to be resistant to penicillins, erythromycin, and/or tetracycline.58, 59
Mupirocin does not appear to be appreciably absorbed systemically following topical application to intact skin.3, 7, 56, 78, 91, 92, 93, 94, 95, 98 Penetration into deeper epidermal skin layers and possible systemic circulation may occur following application to traumatized or diseased skin.3, 7
In one study in healthy adults, less than 0.3% of a topical dose of radiolabeled mupirocin was absorbed through intact skin after 24 hours under an occlusive dressing;3, 7, 56 the drug was not detected in urine or feces collected for 5 days after the dose.3, 7, 56 In this study, 2-4% of the radioactivity was present in the stratum corneum 24 hours after application and remained detectable there for at least 72 hours after application.7
Following topical application of radiolabeled mupirocin ointment to the lower arm of healthy adults and occlusion for 24 hours, there was no measurable systemic absorption (less than 1.1 ng/mL);92, 93, 94, 95 measurable radioactivity was present in the stratum corneum 72 hours after topical application of the ointment.92, 93, 94, 95
Following topical application of mupirocin ointment for dermatologic use containing 2% mupirocin in a vehicle without PEG (Centany®) to an area of 400 cm2 on the back of healthy volunteers once daily for 7 days, some systemic absorption of the drug occurred since 0.2-3% of the administered dose was excreted in urine as monic acid (a metabolite of mupirocin) over 24 hours following the last dose.91
Following topical application of mupirocin calcium cream for dermatologic use (2% mupirocin) to various skin lesions (exceeding 10 cm in length or 100 cm2 in total area) 3 times daily for 5 days in adults 29-60 years of age and children 3-12 years of age, monic acid was detected in urine.78, 98 In this study, percutaneous absorption was reported more frequently in children (90%) than in adults (44%);78, 98 however, the manufacturer states that the degree of percutaneous absorption was minimal in both groups.78, 98
Following intranasal application of mupirocin calcium ointment for intranasal use (2% mupirocin) 3 times daily for 3 days in healthy adults, there was no evidence of systemic absorption of the drug.74 Although serum and urinary concentrations of monic acid and urinary concentrations of mupirocin were below the limits of detection, it was suggested that a mean of 3.3% (range 1.2-5.1%) of a dose of mupirocin calcium ointment for intranasal use could possibly be absorbed systemically from the nasal mucosa of adults.74
The pharmacokinetics of intranasal mupirocin have not been adequately characterized in neonates or children younger than 12 years of age.74 However, there is some evidence that substantial systemic absorption can occur if mupirocin calcium ointment for intranasal use is administered intranasally in neonates and premature infants.74
Mupirocin is highly bound to serum proteins (95-97% or more) in vitro.3, 12, 74, 78, 91, 92, 93, 94, 95, 98
Mupirocin crosses the placenta in rats and rabbits following IV administration;80 it is not known whether the drug crosses the placenta in humans.80
It is not known whether mupirocin is distributed into milk.74, 78, 91, 92, 93, 94, 95, 98
Following IV or oral administration, mupirocin is rapidly metabolized.74, 78, 91, 92, 93, 94, 95, 98 The drug is almost completely metabolized, presumably in the liver,3, 7 by conversion to monic acid.3, 7, 74, 78, 91, 92, 93, 94, 95, 98 Monic acid is formed by de-esterification of the drug at the ester linkage between the ring structure and side chain;7, 80 the metabolite is microbiologically inactive and eliminated in urine.7, 74, 78, 80, 91, 92, 93, 94, 95, 98 Following IV administration of a single 125- or 252-mg IV dose of mupirocin as the sodium salt in healthy adults, approximately 0.5 or 5% of the dose, respectively, is excreted in urine as unchanged mupirocin and 72 or 56%, respectively, is excreted as monic acid within 12 hours.7
Serum concentrations of mupirocin decline in a biphasic manner following IV administration.7, 56, 80 Following IV administration in healthy adults, the elimination half-life of mupirocin is 20-40 minutes74, 78, 91, 92, 93, 94, 95, 98 and that of monic acid is 30-80 minutes.74, 78, 91, 92, 93, 94, 95, 98
There is some evidence that enzymes present within skin can partially inactivate mupirocin by metabolizing the drug to monic acid.7, 80 In an in vitro study using a homogenate of human skin, approximately 3% of a dose of mupirocin was metabolized to monic acid over 48 hours,7, 80 although similar in vitro studies using a homogenate of rat or rabbit skin indicated that up to 27% of a dose of the drug may be inactivated over 48 hours.7 It is doubtful whether this inactivation could occur to an appreciable extent following topical application to intact skin,27 and the drug appears to be active for at least 24 hours when applied topically to such skin.7 Any mupirocin that is absorbed systemically following topical application presumably is inactivated by conversion to monic acid and rapidly eliminated in urine.7, 56, 78, 80 Mupirocin does not appear to be inactivated by nonspecific esterases present in blood.7, 80
Following topical application of mupirocin calcium cream (2% mupirocin) to various skin lesions (exceeding 10 cm in length or 100 cm2 in total area) in adults 29-60 years of age and children 3-12 years of age, urinary concentrations of the drug ranged from undetectable to 10 mcg/mL in adults and undetectable to 1.3 mcg/mL in children.78, 98
Following intranasal application of mupirocin calcium ointment for intranasal use 3 times daily for 3 days in healthy adults, concentrations of mupirocin in urine and concentrations of monic acid in urine and serum were below the limits of detection for up to 72 hours after application.74
Mupirocin is an antibiotic produced by fermentation of Pseudomonas fluorescens .3, 4, 5, 6, 8, 13, 16, 17, 22, 23, 30, 31, 74, 78, 80, 91, 92, 93, 94, 95, 98, 110, 111 The drug is a pseudomonic acid and is structurally unrelated to other currently available anti-infective agents.5, 6, 8, 13, 17, 31, 40, 80 Mupirocin (pseudomonic acid A) is the major fermentation metabolite of Ps. fluorescens exhibiting antimicrobial activity;3, 4, 5, 8, 12, 31, 80 minor fermentation metabolites structurally similar to mupirocin and possessing similar yet less potent antimicrobial activity have been identified as pseudomonic acids B, C, and D.3, 5, 8, 12, 80
Mupirocin is commercially available as the base91, 92, 93, 94, 95 and as the calcium salt.74, 78, 98 Mupirocin occurs as a white to off-white powder and has solubilities of 1 mg/mL in water and 0.5 mg/mL in alcohol at 20°C.66 The drug has a pKa of 5 at 22°C.66
For dermatologic use, mupirocin base is commercially available as a 2% ointment in a water-miscible vehicle containing polyethylene glycol (PEG) (generic)92, 93, 94, 95 or a 2% ointment in a vehicle without PEG (Centany®).91 In addition, mupirocin calcium (2:1) dihydrate cream containing 2% mupirocin in an oil and water-based emulsion is commercially available for dermatologic use (Bactroban®, generic).78, 98
For intranasal use, mupirocin is commercially available as mupirocin calcium (2:1) dihydrate containing 2% mupirocin in a soft white ointment base formulated with paraffin and a mixture of glycerin esters (Softisan® 649) (Bactroban® Nasal).74
Potency of mupirocin calcium cream for dermatologic use and mupirocin calcium ointment for intranasal use is expressed in terms of mupirocin.74, 78, 98
Mupirocin 2% ointment for dermatologic use (formulated with or without PEG) should be stored at 20-25°C.91, 92, 93, 94, 95
Mupirocin calcium cream for dermatologic use should be stored at 20-25°C98 and should not be frozen.78
Mupirocin calcium ointment for intranasal use should be stored at 20-25°C, but may be exposed to temperatures of 15-30°C.74 The intranasal ointment should not be refrigerated.74
Mupirocin is inactivated at pH less than 4 or greater than 9.5, 80 The drug is stable for 24 hours at 37°C in citrated blood.16
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Topical | Ointment | 2%* | Centany® | Medimetriks |
Mupirocin Ointment |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Nasal | Ointment | 2.15% w/w (equivalent to 2% mupirocin) | Bactroban® Nasal | GlaxoSmithKline |
Topical | Cream | 2.15% w/w (equivalent to 2% mupirocin)* | Bactroban® | GlaxoSmithKline |
Mupirocin Cream |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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