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Mupirocin: A new topical therapy for impetigo
Louis Cliff Littlefield, Pharm D Professor of Pharmacy, College of Pharmacy The University of Texas at Austin and Assistant Dean for Pharmacy Education The University of Texas Health Science Center at San Antonio
Mupirocin: Carla
A New Topical Therapy . for Impetigo .
D. Putnam
and Maryann
S. Reynolds,
Pharm
D
1
Impetigo is a superficial skin infection that occurs most commonly on exposed areas of the body such as the face and legs. Group A B-hemolytic streptococci and staphylococci are the most frequent causative organisms. Impetigo occurs most commonly in children. The infection begins as an erythematous macule that rapidly forms a pustule and then ruptures. As the purulent drainage dries, a thick yellowish crust forms on the skin. These lesions are superficial and do not infiltrate the dermis. Systemic signs of infection usually are not present, but lymphadenopathy may occur. Acute glomerulonephritis is a rare but serious complication of impetigo. Impetigo is an indolent yet self-limited infection that should be treated immediately to decrease morbidity and prevent spread of the infection to other foci, as well as to other persons. Successful treatment of impetigo, however, does not alter the incidence of acute glomerulonephritis. Penicillin is the drug of choice for the treatment of impetigo inasmuch as most cases result from streptococci. Efficacy of systemic therapy has been superior to topical therapy with neosporin-bacitracin preparations (Burnett, 1963). Mupirocin, formerly known as pseudomonic acid A, is a new topical antibiotic that is efficacious in the treatment of impetigo. The chemical structure of mupirocin is shown in Figure 1. Produced from a strain Carla D. Putnam is a second-year Doctor of Pharmacy student at the College of Pharmacy, The University of Texas at Austin, and the Department of Pharmacology, The University of Texas Health Science Center at San Antonio. Maryann S. Reynolds, Pharm D, is Assistant Professor and Assistant Director of Drug information Services, Department of Pharmacology, The University of Texas Health Science Center at San Antonio, and Clinical Assistant Professor, College of Pharmacy, The University of Texas at Austin.
224
of Pseudomonm jumescem, it differs from other antibiotics in its unique structure, mechanism of action, and water-miscible formulation (Reilly & Spencer, 1984). It is indicated for the treatment of impetigo caused by Staphylococcusaurezrs, B-hemolytic streptococcus, and StreptococcuspyoBe%es. w PHARMACOLOGY
Mupirocin inhibits ribonucleic acid (RNA) and protein synthesis in susceptible bacteria by reversibly binding to the isoleucyl-transfer-RNA synthetase enzyme (Hughes & Mellows, 1978). It is bacteriostatic at lower concentrations but with prolonged exposure kills 90% to 99% of susceptible bacteria over a period of 24 hours (Sutherland, Boon, Griffin, Masters, Slocombe, & White, 1985). Because of its unique mechanism of action, cross-resistance with other antimicrobials is minimal. n
ANTIBACTERIAL
ACTIVITY
Mupirocin is highly active against staphylococci, including methicillin-resistant Stapbylcoccus aure5i.f (MRSA) and Streptowcczcsspp. (excluding StreptowcCM bon+, S. jiicdti, and S. j&e&m) at low minimum inhibitory concentrations (MIC) (0.06 to 0.5 Fg/ml) . Erysipelothti rhkop~tbk and L&via monocytodenes have intermediate susceptibility (MIC 8 Fg/ml). Other gram-positive organisms that are less susceptible include Cmynebdcterium sp. and Microwccm luteus. Anaerobic gram-positive organisms such as Peptostmptowccus anaerobks, Pmpionibacterium antes, Peptowccm prevotii, and Closwidium sp. are less susceptible to mupirocin (MIC >128 Kg/ml). Susceptible gram-negative bacteria include Haemophi&s i@uenzae, Nerjseria flowrrboeae, N. meningitidrj, Branhamella catarhdis, Bmdetella pertu& and
IOURNAL
OF PEDIATRIC
HEALTH
CARE
journal of Pediatric Health Care
Pediatric
W FIGURE 1 Structure
Pasteurella multocida (MIC 0.02 to 0.25 l&ml). Other gram-negative organisms, most anaerobic bacteria, and fungi are much less susceptible. Because of the slow killing by mupirocin, minimum bactericidal concentrations are eightfold to 32-fold higher than corresponding MICs (Sutherland et al., 1985). Mupirocin’s activity is affected by pH. One study reported the lowest MICs occurred at a pH of 5.5, which is approximately equivalent to normal skin pH (Casewell & Hill, 1985). This was the lowest pH that was tested. In another study, diminished bacterial growth at pH 5.0 may have contributed to an improved effect of mupirocin compared with its activity at pH 5.5 (Sutherland et al., 1985). Little effect on mupirocin’s activity was noted with a change in the inoculum size. (The inoculum represents the number of microorganisms necessary to cause an infection.) MICs varied only twofold to fourfold, with a range of inocula up to 5 X 105. Naturally occurring resistance to mupirocin is rare. Casewell and Hill (1985) found no resistant S. aurew isolates in 750 strains tested at concentrations of 2 p,g/ml. Laboratory-induced resistance produced colonies that survived concentrations of 40 kg/ml, but the investigators concluded that it was insignificant because topical mupirocin ointment achieves concentrations up to 20,000 pg/ml. l
PHARMACOKINETICS
Minimal systemic absorption occurs after topical application of mupirocin. Occlusive dressings do not significantly enhance absorption, but it is suspected that damaged skin may permit increased penetration (Ward & Campoli-Richards, 1986). Mupirocin is rapidly degraded in the liver to an inactive metabolite, manic acid. The serum half-life of mupirocin after intravenous injection is approximately 30 minutes, making it an impractical systemic agent (Crook, 1986). Mupirocin is 95% bound to human plasma proteins (Sutherland et al., 1985).
Pharmacology
225
of mupirocin.
n
CLINICAL
TRIALS
Orecchio and Mischler (1986) conducted a multicenter, randomized, double-blind, placebocontrolled study of 304 patients with superficial primary and secondary skin infections. Cases were diagnosed on the basis of bacterial cultures and evaluated for bacteriologic and clinical efficacy after application of 2% mupirocin or the polyethylene glycol vehicle for up to 10 days. Concomitant use of other antibiotics was not permitted. Both clinical and bacteriologic success rates were significantly improved in the treatment group (p < 0.001). Eighty-five percent of patients who received mupirocin achieved a clinical cure or improvement, and 80% of patients had a bacteriologic cure. A skin rash or eruption developed in three patients who received mupirocin and required discontinuation of therapy in two patients. Thirty-eight pediatric patients with either impetigo (n = 36) or ecthyma (n = 2) were evaluated in a double-blind, controlled study (Eells, Mertz, Piovanetti, Peko, & Eaglestein, 1986). Mupirocin 2% or the polyethylene glycol vehicle was applied to the lesions three times daily for 7 to 12 days. Mupirocin was significantly more effective (90%) than the vehicle (38%) in eradicating the pathogenic organisms S. atireM and group A l3-hemolytic streptococci (p < 0.004), but there was no significant difference in clinical improvement. Twenty outpatients participated in an openlabeled trial that evaluated mupirocin for the treatment of primary skin infections (Reilly and Spencer, 1984). Eighteen patients were infected with S. aureus, and two patients were infected with @hemolytic streptococci. Patients applied 2% mupirocin to skin lesions twice daily and were evaluated for improvement at 7 days and 14 days. Fifteen patients required 7 days of treatment, four required 14 days, and one patient withdrew as a result of a burning sensation after application of mupirocin On the basis of bac-
226
Pediatric
Volume 3, Number 4 July-August 1989
Pharmacology
teriologic assessment, 95% of patients were cured at the end of the treatment period. Phillips, Yogev, and Esterly (1985) evaluated 31 pediatric patients with pyoderma of various causes. S. aurew was present in 30 of 31 cultures, and Streptocom4s pyo~enes was the causative organism in one child. Patients applied 2% mupirocin three times daily to infected areas for 7 to 12 days. The use of Burow’s solution compresses was permitted to cleanse the affected area before application of mupirocin. Clinical cures or improvements and bacteriologic cure were seen in all patients, and no adverse effects or laboratory abnormalities were reported. Mupirocin also has been compared with various systemic antibiotics for the treatment of superficial skin infections. Welsh and Saenz (1987) found mupirocin to be superior to systemic ampicillin in a randomized study. Twenty-seven patients treated with topical mupirocin three times daily and 23 patients who received oral ampicillin 500 mg four times daily for 5 to 10 days were evaluated. Mupirocin was signiiicantly more effective than ampicillin in resolving clinical signs and symptoms, 96% and 78%, respectively (p > 0.05). Mupirocin achieved a bacteriologic cure in 96% of patients whereas ampicillin achieved a bacteriologic cure in only 55% (p < 0.002). The clinical failure rate was sixfold lower in the mupirocin group, 4% and 23%, respectively. In a second randomized clinical trial of 61 pediatric patients, dicloxacillin 250 mg administered four times daily was compared with mupirocin 2% applied three times daily for 5 to 10 days (Arrendondo, 1987). The majority of patients had impetigo caused by S. aurew. Clinical and bacteriologic response rates between groups were comparable. In a single-blind study, investigators evaluated topical 2% mupirocin applied three times daily to 79 patients compared with erythromycin, 250 mg four times daily, or cloxacillin, 250 mg four times daily in 50 and 20 patients, respectively (Dux, Fields, & Pollock, 1986). All patients were treated for 7 days. Mupirocin was more effective in resolving clinical signs and symptoms of infection. Clinical cure was achieved in 8 1% of mupirocin-treated patients compared with 70% of patients treated with erythromy& and 65% of patients treated with cloxacillin. No statistical analyses were performed. One mupirocin-treated patient experienced a mild pruritus as a result of topical use. Mupirocin also has been investigated for the eradication of MRSA nasal carriage, and results seem promising (Dacre, Emmerson, & Jenner, 1983).
n
ADVERSE EFFECTS
Mupirocin has been associated with a very low incidence of adverse effects. Contact sensitization is rare (0.08%), and no photosensitivity reactions have been reported. Nonallergic itching, stinging, or rash is reported in fewer than 1% of treated patients (Parenti, Hatfield, & Leyden, 1987; Product Information, 1988). These reactions may have been due to the polyethylene glycol base inasmuch as the frequency of reactions was similar in the mupirocin and control groups (Ward and Campoli-Richards, 1986; Wuite et al., 1985). Intranasal application has been associated with local stinging, soreness, dry skin, and itching (Dacre et al., 1983). A new lanolin-based formulation is being tested for nasal application because the polyethylene glycol vehicle is thought to be associated with nasal irritation (Parenti et al., 1987). n
DRUG INTERACTIONS
No reports of drug interactions with mupirocin have been documented, but a theoretic interaction with chloramphenicol exists. An in vitro study demonstrated that chloramphenicol interferes with mupirocin inhibition of RNA synthesis, but the clinical significance of this effect is unknown (Hughes & Mellows, 1978). n
DOSAGE AND AVAILABILITY
Mupirocin is marketed by Beecham Pharmaceuticals under the trade name Beoban. It is available by prescription as a 2% ointment in a water-soluble polyethylene glycol vehicle. This formulation is nonocclusive to avoid impairment of reepithelialization (Rumsfield, West, & Aronson, 1986). Recommended frequency of application is three times daily for 5 to 14 days. Patients not responding afier 3 to 5 days should be reevaluated (Product Information, 1988). Oral and parenteral dose forms are not available because of rapid and extensive conversion to an inactive metabolite (Parenti et al., 1987). n
SUMMARY
Mupirocin is a new, topical antibiotic effective for the treatment of impetigo. It has a unique structure, mechanism of action, and water-miscible formulation. When it is applied to an infected area three times daily, clinical improvement should be seen in 85% to 100% of patients within 3 to 5 days. It is associated with a low incidence of adverse effects and cross-resistance. Further studies are necessary to define the exact role of mupirocin in treating other primary and secondary cutaneous infections. n
Journal of Pediatric Health Care
REFERENCES Arrendondo, J. L. (1987). Efficacy and tolerance of topical mupirocin compared with oral dicloxacillin in the treatment of primary skin infections. Current Therapeutic Research,41, 121127. Burnett J. W. (1963). The route of antibiotic administration in superficial impetigo. New England Journal ofMedicine, 268,7275. Casewell, M. W., & Hill, R. L. (1985). In-vitro activity of mupirocin (‘pseudomonic acid’) against clinical isolates of Staphylococcus aureus. Journal of Antimicrobial Chemotherapy, 15, 523531. Crook, S. J. (1986). Innovation and development in oral and topical antibiotics. Practitionev, 230, 249-256. Dacre, J. E., Ernmerson, A. M., & Jenner, E. A. (1983). Nasal carriage of gentamicin and methicilhn resistant Stupl$owccw aureus treated with topical pseudomonic acid. Lancet, 2, 1036. Dux, P. H., Fields, L., & Pollock, D. (1986). 2% topical mupirocin versus systemic erythromycin and cloxacillin in primary and secondary skin infections. &went Therapeuti Research, 40, 933-940. Eells, L. D., Meres, P. M., Piovanetti, Y., Peko, G. M., & Eaglestein, W. H. (1986). Topical antibiotic treatment of impetigo with mupirocin. Archives of Dermatolom, 122, 1273-1276. Hughes, J., & Mellows, G. (1978). On the mode of action of pseudomonic acid: Inhibition of protein synthesis in Staphylococcus aureus. J Antibiotia (Hobo), 31, 330-335. Mupirocin-a new topical antibiotic. (1988). Medic& Letter on Drugs and Tberapeutiu, 30, 55-56. Orecchio, R. M., & Mischler, T. W. (1986). A double-blind multiclinic comparative trial of mupirocin topical and its vehicle
Pediatric
Pharmacology
227
in the treatment of bacterial skin infections. Current Therapeutic Rerearcb, 39, 82-86. Parenti, M. A., Hatfield, S. M., & Leyden, J. J. ( 1987). Mupirocin: A topical antibiotic with a unique structure and mechanism of action. Clinirnl Pharmacy, 6, 761-770. Phillips, L. M., Yogev, R., & Esterly, N. B. (1985). The efficacy of mupirocin (pseudomonic acid) in the treatment of pyoderma in children. Pediatric Emeyenq Care, 1, 180-183. Product Information: Bactroban. (1988). Bristol, TN: Beecham Laboratories. Reilly, G. D., & Spencer, R. C. (1984). Pseudomonic acid-a new antibiotic for skin infections. Joumd ofAntimi&kl Chemotbeiqy, 13, 295-298. Rumsfield, J., West, D. P., & Aronson, I. K. (1986). Topical mupirocin in the treatment of bacterial skin infections. m Intell&mz and Clinical Phawnaq, 20, 943-948. Sutherland, R., Boon, R. J., Griflin, K. E., Masters, I’. J., Slocombe, B., & White, A. R. (1985). Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use. Antimicvobial &ents and Chemotherapy, 27, 495-498. Ward, A., & Carnpoli-Richards, D. M. (1986). Mupirocin-a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs, 32, 425444. Welsh, O., & Saenz, C. (1987). Topical mupirocin compared with oral ampicillin in the treatment of primary and secondary skin infections. Current Therapeutic Research,41, 114-120. Wuite, J., Davies, B. I., Go, M. J., Lambers, J. C., Jackson, D., Mellows, G., & Tasker, T. C. (1985). Pseudomonic acid, a new antibiotic for topical therapy. Journal of the American Acudemy ofDermat&y, 12, 1026-1031.
Mupirocin: Carla
A New Topical Therapy . for Impetigo .
D. Putnam
and Maryann
S. Reynolds,
Pharm
D
1
Impetigo is a superficial skin infection that occurs most commonly on exposed areas of the body such as the face and legs. Group A B-hemolytic streptococci and staphylococci are the most frequent causative organisms. Impetigo occurs most commonly in children. The infection begins as an erythematous macule that rapidly forms a pustule and then ruptures. As the purulent drainage dries, a thick yellowish crust forms on the skin. These lesions are superficial and do not infiltrate the dermis. Systemic signs of infection usually are not present, but lymphadenopathy may occur. Acute glomerulonephritis is a rare but serious complication of impetigo. Impetigo is an indolent yet self-limited infection that should be treated immediately to decrease morbidity and prevent spread of the infection to other foci, as well as to other persons. Successful treatment of impetigo, however, does not alter the incidence of acute glomerulonephritis. Penicillin is the drug of choice for the treatment of impetigo inasmuch as most cases result from streptococci. Efficacy of systemic therapy has been superior to topical therapy with neosporin-bacitracin preparations (Burnett, 1963). Mupirocin, formerly known as pseudomonic acid A, is a new topical antibiotic that is efficacious in the treatment of impetigo. The chemical structure of mupirocin is shown in Figure 1. Produced from a strain Carla D. Putnam is a second-year Doctor of Pharmacy student at the College of Pharmacy, The University of Texas at Austin, and the Department of Pharmacology, The University of Texas Health Science Center at San Antonio. Maryann S. Reynolds, Pharm D, is Assistant Professor and Assistant Director of Drug information Services, Department of Pharmacology, The University of Texas Health Science Center at San Antonio, and Clinical Assistant Professor, College of Pharmacy, The University of Texas at Austin.
224
of Pseudomonm jumescem, it differs from other antibiotics in its unique structure, mechanism of action, and water-miscible formulation (Reilly & Spencer, 1984). It is indicated for the treatment of impetigo caused by Staphylococcusaurezrs, B-hemolytic streptococcus, and StreptococcuspyoBe%es. w PHARMACOLOGY
Mupirocin inhibits ribonucleic acid (RNA) and protein synthesis in susceptible bacteria by reversibly binding to the isoleucyl-transfer-RNA synthetase enzyme (Hughes & Mellows, 1978). It is bacteriostatic at lower concentrations but with prolonged exposure kills 90% to 99% of susceptible bacteria over a period of 24 hours (Sutherland, Boon, Griffin, Masters, Slocombe, & White, 1985). Because of its unique mechanism of action, cross-resistance with other antimicrobials is minimal. n
ANTIBACTERIAL
ACTIVITY
Mupirocin is highly active against staphylococci, including methicillin-resistant Stapbylcoccus aure5i.f (MRSA) and Streptowcczcsspp. (excluding StreptowcCM bon+, S. jiicdti, and S. j&e&m) at low minimum inhibitory concentrations (MIC) (0.06 to 0.5 Fg/ml) . Erysipelothti rhkop~tbk and L&via monocytodenes have intermediate susceptibility (MIC 8 Fg/ml). Other gram-positive organisms that are less susceptible include Cmynebdcterium sp. and Microwccm luteus. Anaerobic gram-positive organisms such as Peptostmptowccus anaerobks, Pmpionibacterium antes, Peptowccm prevotii, and Closwidium sp. are less susceptible to mupirocin (MIC >128 Kg/ml). Susceptible gram-negative bacteria include Haemophi&s i@uenzae, Nerjseria flowrrboeae, N. meningitidrj, Branhamella catarhdis, Bmdetella pertu& and
IOURNAL
OF PEDIATRIC
HEALTH
CARE
journal of Pediatric Health Care
Pediatric
W FIGURE 1 Structure
Pasteurella multocida (MIC 0.02 to 0.25 l&ml). Other gram-negative organisms, most anaerobic bacteria, and fungi are much less susceptible. Because of the slow killing by mupirocin, minimum bactericidal concentrations are eightfold to 32-fold higher than corresponding MICs (Sutherland et al., 1985). Mupirocin’s activity is affected by pH. One study reported the lowest MICs occurred at a pH of 5.5, which is approximately equivalent to normal skin pH (Casewell & Hill, 1985). This was the lowest pH that was tested. In another study, diminished bacterial growth at pH 5.0 may have contributed to an improved effect of mupirocin compared with its activity at pH 5.5 (Sutherland et al., 1985). Little effect on mupirocin’s activity was noted with a change in the inoculum size. (The inoculum represents the number of microorganisms necessary to cause an infection.) MICs varied only twofold to fourfold, with a range of inocula up to 5 X 105. Naturally occurring resistance to mupirocin is rare. Casewell and Hill (1985) found no resistant S. aurew isolates in 750 strains tested at concentrations of 2 p,g/ml. Laboratory-induced resistance produced colonies that survived concentrations of 40 kg/ml, but the investigators concluded that it was insignificant because topical mupirocin ointment achieves concentrations up to 20,000 pg/ml. l
PHARMACOKINETICS
Minimal systemic absorption occurs after topical application of mupirocin. Occlusive dressings do not significantly enhance absorption, but it is suspected that damaged skin may permit increased penetration (Ward & Campoli-Richards, 1986). Mupirocin is rapidly degraded in the liver to an inactive metabolite, manic acid. The serum half-life of mupirocin after intravenous injection is approximately 30 minutes, making it an impractical systemic agent (Crook, 1986). Mupirocin is 95% bound to human plasma proteins (Sutherland et al., 1985).
Pharmacology
225
of mupirocin.
n
CLINICAL
TRIALS
Orecchio and Mischler (1986) conducted a multicenter, randomized, double-blind, placebocontrolled study of 304 patients with superficial primary and secondary skin infections. Cases were diagnosed on the basis of bacterial cultures and evaluated for bacteriologic and clinical efficacy after application of 2% mupirocin or the polyethylene glycol vehicle for up to 10 days. Concomitant use of other antibiotics was not permitted. Both clinical and bacteriologic success rates were significantly improved in the treatment group (p < 0.001). Eighty-five percent of patients who received mupirocin achieved a clinical cure or improvement, and 80% of patients had a bacteriologic cure. A skin rash or eruption developed in three patients who received mupirocin and required discontinuation of therapy in two patients. Thirty-eight pediatric patients with either impetigo (n = 36) or ecthyma (n = 2) were evaluated in a double-blind, controlled study (Eells, Mertz, Piovanetti, Peko, & Eaglestein, 1986). Mupirocin 2% or the polyethylene glycol vehicle was applied to the lesions three times daily for 7 to 12 days. Mupirocin was significantly more effective (90%) than the vehicle (38%) in eradicating the pathogenic organisms S. atireM and group A l3-hemolytic streptococci (p < 0.004), but there was no significant difference in clinical improvement. Twenty outpatients participated in an openlabeled trial that evaluated mupirocin for the treatment of primary skin infections (Reilly and Spencer, 1984). Eighteen patients were infected with S. aureus, and two patients were infected with @hemolytic streptococci. Patients applied 2% mupirocin to skin lesions twice daily and were evaluated for improvement at 7 days and 14 days. Fifteen patients required 7 days of treatment, four required 14 days, and one patient withdrew as a result of a burning sensation after application of mupirocin On the basis of bac-
226
Pediatric
Volume 3, Number 4 July-August 1989
Pharmacology
teriologic assessment, 95% of patients were cured at the end of the treatment period. Phillips, Yogev, and Esterly (1985) evaluated 31 pediatric patients with pyoderma of various causes. S. aurew was present in 30 of 31 cultures, and Streptocom4s pyo~enes was the causative organism in one child. Patients applied 2% mupirocin three times daily to infected areas for 7 to 12 days. The use of Burow’s solution compresses was permitted to cleanse the affected area before application of mupirocin. Clinical cures or improvements and bacteriologic cure were seen in all patients, and no adverse effects or laboratory abnormalities were reported. Mupirocin also has been compared with various systemic antibiotics for the treatment of superficial skin infections. Welsh and Saenz (1987) found mupirocin to be superior to systemic ampicillin in a randomized study. Twenty-seven patients treated with topical mupirocin three times daily and 23 patients who received oral ampicillin 500 mg four times daily for 5 to 10 days were evaluated. Mupirocin was signiiicantly more effective than ampicillin in resolving clinical signs and symptoms, 96% and 78%, respectively (p > 0.05). Mupirocin achieved a bacteriologic cure in 96% of patients whereas ampicillin achieved a bacteriologic cure in only 55% (p < 0.002). The clinical failure rate was sixfold lower in the mupirocin group, 4% and 23%, respectively. In a second randomized clinical trial of 61 pediatric patients, dicloxacillin 250 mg administered four times daily was compared with mupirocin 2% applied three times daily for 5 to 10 days (Arrendondo, 1987). The majority of patients had impetigo caused by S. aurew. Clinical and bacteriologic response rates between groups were comparable. In a single-blind study, investigators evaluated topical 2% mupirocin applied three times daily to 79 patients compared with erythromycin, 250 mg four times daily, or cloxacillin, 250 mg four times daily in 50 and 20 patients, respectively (Dux, Fields, & Pollock, 1986). All patients were treated for 7 days. Mupirocin was more effective in resolving clinical signs and symptoms of infection. Clinical cure was achieved in 8 1% of mupirocin-treated patients compared with 70% of patients treated with erythromy& and 65% of patients treated with cloxacillin. No statistical analyses were performed. One mupirocin-treated patient experienced a mild pruritus as a result of topical use. Mupirocin also has been investigated for the eradication of MRSA nasal carriage, and results seem promising (Dacre, Emmerson, & Jenner, 1983).
n
ADVERSE EFFECTS
Mupirocin has been associated with a very low incidence of adverse effects. Contact sensitization is rare (0.08%), and no photosensitivity reactions have been reported. Nonallergic itching, stinging, or rash is reported in fewer than 1% of treated patients (Parenti, Hatfield, & Leyden, 1987; Product Information, 1988). These reactions may have been due to the polyethylene glycol base inasmuch as the frequency of reactions was similar in the mupirocin and control groups (Ward and Campoli-Richards, 1986; Wuite et al., 1985). Intranasal application has been associated with local stinging, soreness, dry skin, and itching (Dacre et al., 1983). A new lanolin-based formulation is being tested for nasal application because the polyethylene glycol vehicle is thought to be associated with nasal irritation (Parenti et al., 1987). n
DRUG INTERACTIONS
No reports of drug interactions with mupirocin have been documented, but a theoretic interaction with chloramphenicol exists. An in vitro study demonstrated that chloramphenicol interferes with mupirocin inhibition of RNA synthesis, but the clinical significance of this effect is unknown (Hughes & Mellows, 1978). n
DOSAGE AND AVAILABILITY
Mupirocin is marketed by Beecham Pharmaceuticals under the trade name Beoban. It is available by prescription as a 2% ointment in a water-soluble polyethylene glycol vehicle. This formulation is nonocclusive to avoid impairment of reepithelialization (Rumsfield, West, & Aronson, 1986). Recommended frequency of application is three times daily for 5 to 14 days. Patients not responding afier 3 to 5 days should be reevaluated (Product Information, 1988). Oral and parenteral dose forms are not available because of rapid and extensive conversion to an inactive metabolite (Parenti et al., 1987). n
SUMMARY
Mupirocin is a new, topical antibiotic effective for the treatment of impetigo. It has a unique structure, mechanism of action, and water-miscible formulation. When it is applied to an infected area three times daily, clinical improvement should be seen in 85% to 100% of patients within 3 to 5 days. It is associated with a low incidence of adverse effects and cross-resistance. Further studies are necessary to define the exact role of mupirocin in treating other primary and secondary cutaneous infections. n
Journal of Pediatric Health Care
REFERENCES Arrendondo, J. L. (1987). Efficacy and tolerance of topical mupirocin compared with oral dicloxacillin in the treatment of primary skin infections. Current Therapeutic Research,41, 121127. Burnett J. W. (1963). The route of antibiotic administration in superficial impetigo. New England Journal ofMedicine, 268,7275. Casewell, M. W., & Hill, R. L. (1985). In-vitro activity of mupirocin (‘pseudomonic acid’) against clinical isolates of Staphylococcus aureus. Journal of Antimicrobial Chemotherapy, 15, 523531. Crook, S. J. (1986). Innovation and development in oral and topical antibiotics. Practitionev, 230, 249-256. Dacre, J. E., Ernmerson, A. M., & Jenner, E. A. (1983). Nasal carriage of gentamicin and methicilhn resistant Stupl$owccw aureus treated with topical pseudomonic acid. Lancet, 2, 1036. Dux, P. H., Fields, L., & Pollock, D. (1986). 2% topical mupirocin versus systemic erythromycin and cloxacillin in primary and secondary skin infections. &went Therapeuti Research, 40, 933-940. Eells, L. D., Meres, P. M., Piovanetti, Y., Peko, G. M., & Eaglestein, W. H. (1986). Topical antibiotic treatment of impetigo with mupirocin. Archives of Dermatolom, 122, 1273-1276. Hughes, J., & Mellows, G. (1978). On the mode of action of pseudomonic acid: Inhibition of protein synthesis in Staphylococcus aureus. J Antibiotia (Hobo), 31, 330-335. Mupirocin-a new topical antibiotic. (1988). Medic& Letter on Drugs and Tberapeutiu, 30, 55-56. Orecchio, R. M., & Mischler, T. W. (1986). A double-blind multiclinic comparative trial of mupirocin topical and its vehicle
Pediatric
Pharmacology
227
in the treatment of bacterial skin infections. Current Therapeutic Rerearcb, 39, 82-86. Parenti, M. A., Hatfield, S. M., & Leyden, J. J. ( 1987). Mupirocin: A topical antibiotic with a unique structure and mechanism of action. Clinirnl Pharmacy, 6, 761-770. Phillips, L. M., Yogev, R., & Esterly, N. B. (1985). The efficacy of mupirocin (pseudomonic acid) in the treatment of pyoderma in children. Pediatric Emeyenq Care, 1, 180-183. Product Information: Bactroban. (1988). Bristol, TN: Beecham Laboratories. Reilly, G. D., & Spencer, R. C. (1984). Pseudomonic acid-a new antibiotic for skin infections. Joumd ofAntimi&kl Chemotbeiqy, 13, 295-298. Rumsfield, J., West, D. P., & Aronson, I. K. (1986). Topical mupirocin in the treatment of bacterial skin infections. m Intell&mz and Clinical Phawnaq, 20, 943-948. Sutherland, R., Boon, R. J., Griflin, K. E., Masters, I’. J., Slocombe, B., & White, A. R. (1985). Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use. Antimicvobial &ents and Chemotherapy, 27, 495-498. Ward, A., & Carnpoli-Richards, D. M. (1986). Mupirocin-a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs, 32, 425444. Welsh, O., & Saenz, C. (1987). Topical mupirocin compared with oral ampicillin in the treatment of primary and secondary skin infections. Current Therapeutic Research,41, 114-120. Wuite, J., Davies, B. I., Go, M. J., Lambers, J. C., Jackson, D., Mellows, G., & Tasker, T. C. (1985). Pseudomonic acid, a new antibiotic for topical therapy. Journal of the American Acudemy ofDermat&y, 12, 1026-1031.