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PubMed1989

Failure of mupirocin-resistant staphylococci to inactivate mupirocin.

Isolates from four UK centres, comprising four Staphylococcus aureus strains and one Staphylococcus epidermidis strain with high-level mupirocin resistance, and one strain each of Staphylococcus aureus and Staphylococcus epidermidis with low-level mupirocin resistance, were assessed for intracellular or extracellular enzymatic alteration of the antibiotic. No change was seen in a number of assays, which included comparative disk diffusion, well diffusion and high-pressure liquid chromatography. Other mechanisms of resistance need to be explored in these isolates.

Anti-Bacterial Agents↗

PubMed1989

Mechanism of mupirocin transport into sensitive and resistant bacteria.

Pseudomonic acid A (mupirocin) blocks protein synthesis in bacteria by inhibition of bacterial isoleucyl-tRNA synthetase. [16, 17-3H]mupirocin, isolated from a methionine auxotroph of Pseudomonas fluorescens, was used to study transport of this antibiotic into sensitive and resistant strains of Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. The transport of mupirocin into sensitive bacteria was energy independent and temperature dependent (decreased uptake at lower temperatures), indicating non-carrier-mediated passive diffusion. Uptake was also saturable with time or increasing antibiotic concentration. The saturable intracellular binding site, most likely the target isoleucyl-tRNA synthetase as determined by the amount of bound mupirocin (2,700 to 3,100 molecules per cell), caused concentration of the antibiotic within the cell. E. coli transformed with a plasmid containing ileS overproduced the target enzyme and demonstrated greater accumulation of mupirocin than a strain containing a control plasmid. The concentrations needed to half saturate (Kd) these binding sites in B. subtilis and S. aureus were 35 and 7 nM, respectively. In gram-positive organisms trained for mupirocin resistance, uptake was not saturable with increasing antibiotic concentration, and intra- and extracellular concentrations of drug equilibrated with time. Kinetic analysis of crude isoleucyl-tRNA synthetase from trained and untrained B. subtilis strains revealed differences in apparent Ki for mupirocin (resistant strain SB23T, Ki = 71.1 nM; sensitive strain SB23, Ki = 33.5 nM), while the Km for isoleucine remained unchanged (2.7 to 2.9 microM). A Km of 0.4 micromolar isoleucine and Ki of 24 nM mupirocin was demonstrated for isoleucyl-tRNA synthetase from sensitive S. aureus 730a, while no isoleucyl-tRNA synthetase activity was detected in extracts of resistance-trained S. aureus 3000 even at 40 micromolar isoleucine, suggesting instability of the enzyme. Free isoleucine pools differed between sensitive (0.26 micromolar) and resistance-trained (1.06 micromolar) S. aureus. Our results demonstrate that (i) mupirocin enters cells by passive diffusion, (ii) mupirocin concentrates in sensitive bacteria due to binding to isoleucyl-tRNA synthetase, and (iii) resistance to mupirocin involves restricted access to the binding site of isoleucyl-tRNA synthetase.

Amino Acids↗

PubMed1987

Effect of mupirocin on the growth and lifespan of human fibroblasts.

We have examined the effect of the antibiotic mupirocin on the growth and proliferative lifespan of human fibroblasts. Human embryonic lung fibroblasts were grown in Dulbecco's minimal essential medium, containing 10% fetal bovine serum and various concentrations of mupirocin ranging from 0.5-756 micrograms/ml. There is little difference in the rate of exponential growth and the final saturation density reached between control cultures and those grown in 0.5 microgram, 72 micrograms, or 76 micrograms/ml mupirocin. Growth was retarded or inhibited in cultures containing 650-750 micrograms/ml mupirocin. The proliferative lifespan of adult skin fibroblasts was examined in cultures serially subcultivated in medium containing either 7 micrograms/ml or 100 micrograms/ml mupirocin. Cultures incubated in these concentrations of mupirocin were capable of reaching their full proliferative potential. This study shows that the growth and proliferative lifespan of human fibroblasts is unaltered in the presence of at least 100 micrograms/ml mupirocin although growth of human fibroblasts is inhibited by 700 micrograms/ml mupirocin. These observations suggest that long-term use of low but bactericidal concentrations of mupirocin will not impair growth of fibroblasts in healing wounds.

Cell Adhesion↗

PubMed1987

Mupirocin: a topical antibiotic with a unique structure and mechanism of action.

The chemistry, mechanism of action, antimicrobial activity, pharmacokinetics, clinical efficacy, adverse effects, dosage, and administration of mupirocin are reviewed. Mupirocin, formerly termed pseudomonic acid A, is a topical antibiotic under investigation for the treatment of impetigo and other superficial primary and secondary skin infections. Mupirocin (Bactroban, Beecham Laboratories) is currently formulated as a 2% ointment in a water-miscible polyethylene glycol base. The drug is a unique antimicrobial agent because of its structure and mechanism of action. Mupirocin apparently exerts its antimicrobial activity by reversibly inhibiting isoleucyl-transfer RNA, thereby inhibiting bacterial protein and RNA synthesis. Mupirocin has excellent in vitro activity against staphylococci and most streptococci but less activity against other gram-positive and gram-negative bacteria. The drug will only be used topically because of its rapid and extensive systemic metabolism. Several controlled clinical trials documented that mupirocin was significantly better than the polyethylene glycol vehicle alone or ampicillin and as effective as cloxacillin, dicloxacillin, or erythromycin in producing clinical and bacteriological cures in patients with impetigo and wound infections caused by gram-positive pathogens. Limited studies suggest that mupirocin may also have a role in eradicating nasal carriage of staphylococci. Reported adverse effects are local and may be related to the polyethylene glycol vehicle base. Mupirocin should be useful for treating patients with impetigo and wound infections caused by Staphylococcus aureus. However, additional controlled, comparative clinical studies are needed to identify the role of mupirocin in treating other primary and secondary skin infections and for eliminating nasal carriage of staphylococci.

Administration, Topical↗

PubMed1991

Reduction in the colonization of central venous cannulae by mupirocin.

In an in-vitro simulation of an intravascular cannula enclosed in a fibrin sheath, 0.03 mg1(-1) of mupirocin prevented significant colonization [greater than 15 colony forming units (cfu)] by two clinical isolates of Staphylococcus epidermidis and one each of S. saprophyticus, S. hominis and S. haemolyticus. This suggests that in vivo, where protein binding of mupirocin is 95-97%, 1 mg 1(-1) of mupirocin at the cannula surface would be required to prevent colonization. These results support the findings of our previously published prospective controlled trial, in which mupirocin applied to the insertion sites of 172 internal jugular cannulae reduced the rate of colonization of cannula tips to 5%, compared with 25% for the 186 controls (P less than 0.001). Of the 46 colonized cannula tips from 110 control patients, the same species was isolated from the skin of the insertion site in 67% and from the lumen flush in only 15%. Analysed by patient, mupirocin reduced the proportion of patients with colonized tips from 17% to 3% after 24 h of infection, and from 35 to 10% after 48 h (P = 0.002). The use of agar containing charcoal, as a mupirocin neutralizer, and the incubation of tip-culture plates flooded with the Oxford staphylococcus, gave no evidence of carry over of mupirocin onto cannulae removed from mupirocin-treated patients.

Administration, Topical↗

PubMed1985

In-vitro activity of mupirocin ('pseudomonic acid') against clinical isolates of Staphylococcus aureus.

The in-vitro activity of mupirocin ('pseudomonic acid') was determined against clinical isolates of Staphylococcus aureus with various antibiotic resistance patterns including resistance to methicillin. All 750 isolates were inhibited by 2 mg/l of mupirocin and the MICs for 200 isolates tested on DST agar at pH 7.2 with an inoculum of 10(4) cfu ranged from 0.015 to 0.06 mg/l. Inoculum size, pH, test agar and the method of dissolving mupirocin all influenced the MICs obtained. The minimum concentrations of mupirocin to obtain a 99, and 99.9 and 99.99% kill after 24 h in Iso-Sensitest broth at pH 7.2 were 2-4, 16 and 32 mg/l, respectively. Sterile cultures were obtained when each of five strains were exposed to 1.0 mg/l or more of mupirocin for 120 h. Resistant variants with MICs of up to 4 mg/l were detected at a frequency of approximately 1 X 10(-9) and produced chrome-yellow colonies. Each of five strains could be trained to grow in the presence of 40 mg/l of mupirocin. We conclude that although apparently bacteriostatic, mupirocin has slow bactericidal activity against Staph. aureus and that 2% mupirocin may well be effective for topical treatment of skin infections caused by Staph. aureus and contribute to the control of multiply-resistant strains during hospital outbreaks.

Anti-Bacterial Agents↗

PubMed1989

The influence of calcium mupirocin nasal ointment on the incidence of Staphylococcus aureus infections in haemodialysis patients.

Mupirocin was used in haemodialysis patients in an attempt to eradicate nasal carriage of Staphylococcus aureus and to prevent infection caused by this microorganism. The effectiveness of calcium mupirocin as a 2% nasal ointment OB2 (16 patients for 104 patient-months) was compared to that of placebo (18 patients for 147 patient-months) in a double-blind study. Mupirocin or placebo were applied in both anterior nares thrice daily for 2 weeks and subsequently three times weekly for a total of 9 months. During therapy, S. aureus was recovered from only 6% of the nasal cultures in the mupirocin group compared to 58% in the placebo group (P less than or equal to 0.01). Only one S. aureus infection was documented in the mupirocin group compared to six in the placebo group (P less than or equal to 0.05). The S. aureus strain causing the single infection in the mupirocin group was of a different phage type to that of the original nasal strain. In contrast, at least four of the six strains causing infection in the placebo group were of similar phage type to the original nasal strain. All S. aureus isolates remained mupirocin sensitive (MIC less than or equal to 1 mg/l). In conclusion, mupirocin nasal ointment was effective in eradicating nasal carriage of S. aureus and in preventing S. aureus infections in patients on haemodialysis.

Administration, Intranasal↗

PubMed1990

Mupirocin for the reduction of colonization of internal jugular cannulae--a randomized controlled trial.

In a prospective study, 218 cardiothoracic patients, in whom 'Abbocath-T' cannulae had been inserted preoperatively into the internal jugular vein, were randomized to receive skin preparation of the insertion site with tincture of iodine (108 controls) or tincture of iodine followed by application of sterile 2% calcium mupirocin ointment (110 test patients). Cannulae were usually removed within 48 h of the operation. Patients receiving mupirocin were less likely to develop significant colonization of one or more of their cannulae as judged by Maki's criterion of a yield of greater than 15 colony forming units (cfu) from a cannula segment rolled on an agar plate (17% of mupirocin treated patients compared with 54% of the controls, P less than 0.001). Coagulase-negative staphylococci, micrococci, or both, were the commonest isolates and were cultured from 70% of the 186 control cannulae compared with 24% of 172 cannulae inserted through mupirocin-treated skin (P less than 0.001). A count of more than 15 cfu was found on the tips of 25% control cannulae compared with 5% of the cannulae from mupirocin-treated patients, an effect which was independent of in-situ time (P less than 0.001). For cannulae with colonized tips, the same species was isolated from the skin of the insertion site in 67%, from the exterior of the hub in 61% and from the lumen in only 15%. There were no side effects attributed to mupirocin or superinfection with resistant organisms. We conclude that in cardiothoracic patients the application of mupirocin after standard skin preparation with tincture of iodine significantly reduces the colonization of central venous cannulae by organisms derived from the skin insertion site.

Adolescent↗

PubMed1986

Topical mupirocin in the treatment of bacterial skin infections.

Mupirocin is an investigational topical antibiotic used for treatment and prophylaxis of bacterial skin infections. Mupirocin differs from other antibiotics in its synthesis, structure, and mechanism of action. In vitro, mupirocin possesses antimicrobial activity against staphylococci, streptococci, Hemophilus influenzae, and Neisseria gonorrhoeae. Few studies comparing mupirocin to other topical antibiotics are available. Initial studies comparing mupirocin to inactive vehicle in the treatment of impetigo indicate an overall 92 percent pathogen eradication rate with active drug and 58 percent eradication rate with vehicle. Overall response to treatment of secondary skin infections was favorable in 91 percent of patients treated with mupirocin and 77 percent of those treated with vehicle. Although incidence is not greater than placebo, adverse effects have included pruritus, burning, dry skin, and erythema. Additional trials and clinical use should further help determine the role of mupirocin in the treatment of minor, primary, and secondary skin infections.

Anti-Bacterial Agents↗

PubMed1991

Elimination of coincident Staphylococcus aureus nasal and hand carriage with intranasal application of mupirocin calcium ointment.

OBJECTIVE: To determine the safety and efficacy of mupirocin calcium ointment in the elimination of Staphylococcus aureus nasal and hand carriage in healthy persons. DESIGN: A double-blind, placebo-controlled, randomized trial. SETTING: Clinical research unit of a tertiary medical center. SUBJECTS: Health care workers with stable S. aureus nasal carriage. INTERVENTIONS: Subjects (n = 68) were randomly assigned to receive either mupirocin or placebo intranasally twice daily for 5 days. MEASUREMENTS AND MAIN RESULTS: Cultures of the hands and nares were obtained at baseline and 72 hours after therapy. The nares were also cultured 1, 2, 4, and 12 weeks after therapy. Antimicrobial susceptibility testing and restriction endonuclease analysis of plasmid DNA were used to confirm strain identity. There were no serious side effects. Mupirocin decreased the frequency of S. aureus nasal carriage at each time interval: At 3 months, 71% of subjects receiving mupirocin remained free of nasal S. aureus compared with 18% of controls. This difference (53%; 95% CI; 26% to 80%) was significant (P less than 0.0001). Additionally, analysis of plasmid patterns showed that 79% of subjects in the mupirocin group were free of the initial colonizing strain at 3 months. The proportion of hand cultures positive for S. aureus in the mupirocin group after therapy was lower than in the placebo group (2.9% compared with 57.6%). This difference (53%; 95 CI, 30% to 80%) was significant, after adjustment for the frequency of hand carriage at baseline (P less than 0.0001). CONCLUSIONS: When applied intranasally for 5 days, mupirocin calcium ointment is safe and effective in eliminating S. aureus nasal carriage in healthy persons for up to 3 months and appears to have a corresponding effect on hand carriage at 72 hours after therapy.

Administration, Intranasal↗

PubMed1992

Treatment of Staphylococcus aureus nasal carriers in CAPD with mupirocin.

We have studied the efficacy of topical Mupirocin for elimination of Staphylococcus aureus (Staph. aureus) nasal carriage in CAPD patients. Staph. aureus nasal carriers in our CAPD program were randomized to one of two groups: Group 1, treated with Mupirocin, and Group 2, treated with neomycin sulphate nasal ointment. The prevalence of Staph. aureus nasal colonization was 44% for patients (24/54) and 17% for dialysis partners (5/29). Group 1 included 11 patients and 1 partner, and Group 2, 8 patients and 2 partners. In Group 1, the eradication rate was 100%, and the recolonization rate was 0, 8, 41, 55 and 66% at 1, 2, 3, 6 and 10 months. In Group 2, the eradication rate was 40%, with a recolonization rate of 0.25 and 75% at 1, 2 and 3 months. Re-treatment with mupirocin was successful in 66% of the cases, compared to 20% for neomycin. The MIC90 of mupirocin for Staph. aureus was 0.5 mcg/mL, with an increase to 4 mcg/mL towards the end of the study. During the study period, there was a very low incidence of Staph. aureus peritonitis or catheter-related infections in patients treated with mupirocin. Secondary effects of mupirocin were negligible. Mupirocin is more effective than neomycin sulphate for the elimination of Staph. aureus nasal colonization in patients undergoing CAPD. Periodic re-treatment is frequently necessary, given the significant recolonization rate.

Administration, Topical↗

PubMed1989

Topical antibiotics in the treatment of superficial skin infections in general practice--a comparison of mupirocin with sodium fusidate.

A total of 413 eligible patients took part in an observer-blind randomised multicentre clinical trial in order to compare the clinical and bacteriological efficacy of mupirocin (Bactroban) ointment with sodium fusidate (Fucidin) ointment for treating superficial skin infections seen in general practice. Mupirocin was applied twice daily and sodium fusidate thrice daily for a period of 7 days. Both treatments were similarly effective with 97% patients treated with mupirocin and 93% patients treated with sodium fusidate responding. Mupirocin was significantly more effective in the treatment of acute primary skin infections and in the treatment of a subgroup of patients with impetigo (P less than 0.01). Of the organisms detected before treatment began, 93% were not found after treatment with mupirocin compared with 89% after treatment with sodium fusidate. Staphylococcus aureus and/or beta-haemolytic streptococci appeared to be eliminated in significantly more patients treated with mupirocin (96%) compared with those treated with sodium fusidate (88%), (P = 0.03). Both treatments were well tolerated.

Administration, Topical↗

PubMed1989

Topical 2% mupirocin versus 2% fusidic acid ointment in the treatment of primary and secondary skin infections.

The efficacy and side effects of topical mupirocin (Bactroban) and fusidic acid (Fucidin) ointment were compared in a double-blind, randomized trial in 70 patients who came to the Dermatologic Clinic of L'Enfant Jésus Hospital with primary or secondary (or both) skin infections. Thirty-five patients were treated with mupirocin and 35 patients were treated with fusidic acid three times a day for seven days. Clinical and bacteriologic assessments were conducted before and after treatment. The efficacy of mupirocin, in terms of resolution and improvement of clinical signs and symptoms of infection, as well as of the elimination of infecting organisms, was similar to that of fusidic acid. Of 34 patients (1 could not be evaluated) treated with mupirocin, a clinical cure was achieved in 18, and significant improvement was demonstrated in 15. Similarly, of 35 patients treated with fusidic acid, a clinical cure was achieved in 18 and improvement occurred in 15. Bacteriologic cure rates were 97% (30 of 31 patients evaluated) in the mupirocin-treated group, compared with 87% (27 of 31 patients evaluated) in the fusidic acid-treated group. No side effects were observed in either treatment group. Because topical 2% mupirocin has little or no potential for irritation, systemic side effects, or cross-resistance with other antibiotics, its efficacy is likely to make this new compound a useful agent for the treatment of superficial skin infections.

Administration, Topical↗

PubMed1988

Bactericidal efficacy of mupirocin in multi-antibiotic resistant Staphylococcus aureus burn wound infection.

Methicillin resistant Staphylococcus aureus strains (MRSA) have become increasingly prevalent as pathogenic organisms, especially in burn wounds, with an associated mortality of 20-40% among those clinically infected. Mupirocin ointment, a new topical antibiotic, has proved in vitro and in vivo to be highly effective in the treatment of MRSA infections. A modified Walker burn wound model was used to define the rate of trans-eschar penetration, biodynamic availability and bactericidal efficacy of 2% mupirocin ointment in established MRSA burn wound infection. In-vitro penetration trials confirmed the effective diffusion of mupirocin through 1.5 mm eschar within 2 h. A single topical application of mupirocin resulted in a 98.3% (5.67 x 10(8) cfu/g of tissue--1.0 x 10(7) cfu/g of tissue) reduction in intra-eschar viable organisms within 36 h post application. A second topical application of mupirocin at 24 h resulted in a total reduction of 99.6% in viable intra-eschar organisms (1.85 x 10(8) cfu/gram of tissue--6.76 x 10(5) cfu/g of tissue). It is concluded that mupirocin is highly effective in controlling MRSA burn wound infection and should be applied topically every 24 h.

Animals↗

PubMed1988

Randomized clinical trial of topical mupirocin versus oral erythromycin for impetigo.

The safety and efficacy of a new topical antiinfective agent, mupirocin, was compared with that of oral erythromycin ethylsuccinate in the treatment of impetigo in children. Sixty-two children aged 5 months to 13 years with impetigo were assigned to be treated with either mupirocin in three daily applications or erythromycin ethylsuccinate (40 mg/kg of body weight per day divided into four doses) according to a randomized treatment schedule. On the initial visit, exudate or cleansed infected sites or both were cultured and therapy was begun. All patients were treated for 8 days. Patients were seen again on days 4 to 5 of therapy, at the end of therapy, and 7 days after the end of therapy. Sites of infection were comparable between the groups, as were bacteriologic responses. At the first visit, 24 of 30 children in the mupirocin group and 14 of 32 children in the erythromycin group were cured or had at least a 75% reduction in size of the lesions. At the end of the study, all 29 of the children in the mupirocin group who came to follow-up, compared with 27 of 29 in the erythromycin group, were cured. Side effects were few. Five children in the erythromycin group developed mild diarrhea. Thus, mupirocin appears to be safe and effective in treating impetigo in children. Our data show a trend toward more rapid clinical response with mupirocin than with erythromycin.

Administration, Oral↗

PubMed1989

Efficacy of mupirocin in methicillin-resistant Staphylococcus aureus burn wound infection.

Methicillin-resistant Staphylococcus aureus strains (MRSA) have become increasingly prevalent as nosocomial pathogens, especially in burn wounds. MRSA constituted 38% of all S. aureus isolates in our 25-bed burns unit despite the utilization of a combination of 1% silver sulfadiazine and 0.2% chlorhexidine as topical therapy. Mupirocin, a new antibiotic, has proved in vitro and in vivo to be highly effective in the treatment of MRSA infections. A prospective clinical trial with mupirocin ointment in MRSA burn wound infection was untertaken. Forty-five children with 59 discrete burn wounds and from whom MRSA were isolated were treated with 2% mupirocin ointment under occlusive dressings, applied twice daily for 5 days. The average burned area treated was 8% (range, 2 to 20%) of the total body surface area. The burn wounds were assessed clinically and bacteriologically daily. Mupirocin eliminated MRSA in all 59 wounds treated, with the maximum therapeutic response seen within 4 days. In three wounds, gram-negative organisms persisted after 5 days of topical therapy. Treatment was well tolerated by all children. We recommend that mupirocin in its present polyethylene glycol base should be used only on a selective basis, when current prophylactic topical therapy has failed to control MRSA infection in burns of less than 20% of the total body surface area, and that it should be applied only for a limited period of 5 days. The safety and the efficacy of mupirocin in burns exceeding 20% of the total body surface area need to be established.

Anti-Bacterial Agents↗

PubMed1988

A comparison of sodium fusidate ointment and mupirocin ointment in superficial skin sepsis.

Sodium fusidate ointment and mupirocin ointment were compared in 354 patients with superficial skin sepsis. The ointments were applied 3-times daily, or once daily when covered by a dressing, and the response assessed after 6 to 8 days. Both preparations proved effective clinically with 86% of patients responding. There was no difference between the two preparations in cases of primary infection (85% to both ointments), including a sub-group with impetigo (sodium fusidate 88% and mupirocin 84%), or secondary infection (sodium fusidate 81% and mupirocin 89%). Sodium fusidate ointment (98%) was significantly better (p less than 0.05) than mupirocin (82%) in patients with other superficial infections. Both ointments were equally effective in cases where Gram-positive, Gram-negative or mixed Gram-positive/Gram-negative bacteria were isolated. Adverse effects were reported in 1.0% of patients using sodium fusidate ointment and in 7.4% of patients using mupirocin ointment. The majority of complaints concerned the greasiness of mupirocin ointment.

Adolescent↗

PubMed1992

Cost-effectiveness of erythromycin versus mupirocin for the treatment of impetigo in children.

A new topical antibiotic, mupirocin, has been found to be as effective as erythromycin for the treatment of impetigo, but concerns about its expense have been raised. This controlled clinical trial sought to compare the cost-effectiveness of erythromycin (E) and mupirocin (M). Ninety-three children, aged 3 months to 16 years, were randomly assigned to receive 10 days of oral erythromycin (n = 46) or topical mupirocin (n = 47). Costs and effects were measured through structured interviews. Cost per case differed significantly by group (E = $56.85; M = $62.30; P less than .05) due chiefly to extra visits and medication changes needed by those treated with mupirocin. Erythromycin and mupirocin were equally effective. The likelihood of side effects (E = 43%, M = 22%) approached significance (P less than .07); those treated with erythromycin were willing to pay more for a different medicine to avoid the side effects experienced (P less than .05). Working parents and school-age children were more likely to alter their daily activities when the patient was taking erythromycin (P less than .04). Compliance and parental satisfaction did not differ by treatment group; however, parents of children treated with erythromycin were more likely to prefer the alternate drug regimen. It is concluded that the type of medication prescribed can be based on parental preference because the increased cost of mupirocin is offset by increased side effects and number of schooldays and workdays lost with erythromycin.

Baltimore↗