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Drugs

, Volume 32, Issue 5, pp 425–444 | Cite as

Mupirocin

A Review of Its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Use
  • Alan Ward
  • Deborah M. Campoli-Richards
Drug Evaluation

Summary

Synopsis: Mupirocin (pseudomonic acid A) 1 is a novel topical antibacterial agent which inhibits bacterial protein and RNA synthesis. It has excellent in vitro activity against staphylococci and most streptococci, but has less activity against other Gram-positive and most Gram-negative bacteria. Its rapid systemic metabolism means it will only be used topically which, combined with its novel chemical structure, should make cross-resistance less likely to occur than with other currently available topical antibacterial agents.

Mupirocin 2% ointment administered 2 or 3 times daily has shown excellent efficacy in both primary and secondary superficial skin infections, usually with at least 80% of patients being clinically cured or markedly improved, and over 90% eradication of the bacterial pathogen involved. Efficacy in impetigo and, to a somewhat lesser extent, infected wounds has been particularly convincingly demonstrated, while in other secondary skin infections the clinical response seen with mupirocin was often similar to the high success rate of vehicle alone. Limited evidence suggests that mupirocin may be as effective as chlortetracycline, fusidic acid, neomycin and other antibacterial agents, but more controlled, comparative studies are needed. The evidence of efficacy against nasal carriage of Staphylococcus aureus, including methicillin-resistant forms, is encouraging and currently work is being undertaken to improve the acceptability of the vehicle for this use. Side effects are limited to local reactions (in less than 3% of patients) and are no more frequent than observed with the vehicle alone.

Thus, mupirocin appears to be a useful addition to the agents available for the treatment of superficial primary skin infections, such as impetigo, although its precise place in therapy remains to be established.

Antimicrobial Activity: Mupirocin potently inhibits bacterial protein and RNA synthesis, by inhibition of isoleucyl-transfer RNA synthetase. The drug has excellent in vitro antibacterial activity against the primary Gram-positive pathogen involved in skin infections, Staphylococcus aureus, with 90% of strains being inhibited at concentrations (MIC90) of less than 0.12 mg/L. Strains of S. aureus resistant to multiple antibiotics were only slightly less sensitive to mupirocin (MIC ⩽ 2 mg/L), with no evidence of cross-resistance to other drugs. Other staphylococci, including methicillin-resistant strains, and most streptococci, including S. pneumoniae and S. pyogenes are generally inhibited by low concentrations of mupirocin (⩽ 1 mg/L), although Streptococcus faecalis was relatively insensitive (MIC90 32 to 64 mg/L). Other aerobic and anaerobic Gram-positive bacteria are generally only moderately susceptible or resistant to mupirocin.

Many Gram-negative bacteria are resistant to mupirocin, with the exception of Haemophilus infiuenzae, Neisseria meningitidis, Neisseria gonorrhoea, Branhamella catarrhalis, Bordetella pertussis and Pasturella multicoda (MIC ⩽ 0.25 mg/L). In usual in vitro sensitivity tests mupirocin has no activity against Chlamydia trachomatis nor any antifungal activity. The activity of mupirocin is relatively unaffected by media or inoculum size, although mupirocin is most active at moderately acid pH and is greatly inhibited in the presence of serum.

Application of mupirocin to normal skin produces markedly reduced Gram-positive bacterial counts without overgrowth of resistant Gram-positive organisms, or Gram-negative bacteria such as Pseudomonas species. The efficacy of mupirocin has been demonstrated against experimentally induced infections with S. aureus, S. pyogenes, and surprisingly against infections with Pseudomonas aeruginosa and Candida albicans. Successful prophylaxis occurred against S. aureus but not P. aeruginosa infections.

Pharmacokinetics: After topical application mupirocin is only very minimally absorbed systemically (less than 1%), with no detectable concentrations appearing in faecal or urinary output. Penetration into the deeper epidermal and dermal layers is enhanced in traumatised skin and under occlusive dressings. Mupirocin is slowly metabolised by the skin to the antimicrobially inactive metabolite monic acid.

Therapeutic Trials: The therapeutic efficacy of mupirocin 2% ointment applied topically 2 or 3 times daily for 5 to 14 days has been documented in open and vehicle (polyethylene glycol) controlled studies in patients with primary skin infections, and in secondary infection of dermatoses and injured tissue. However, in some types of disease only very limited numbers of patients have been studied, and there are few data comparing the efficacy of mupirocin with other commercially available topical antibacterial agents.

Open and vehicle-controlled studies in patients with a variety of primary skin infections have consistently shown mupirocin to be clinically effective in at least 80% of patients, with higher success rates in patients with acute infections than in those with chronic disease. Results with vehicle alone have been more variable, ranging from about 25 to 85% response depending upon the type and severity of patient infection being treated. Particularly good success rates with mupirocin have been achieved in patients (usually children) with impetigo, most studies reporting clinical cure or marked improvement in at least 95% of the patients. In limited comparative trials, mupirocin appears to be superior to vehicle and neomycin 1% ointment, and at least as effective as fusidic acid 2% ointment in patients with impetigo, and as effective as chlortetracycline 3% in a variety of superficial skin infections.

In secondary infections, mupirocin was clearly bacteriologically superior to vehicle, with overall eradication rates of 90 and 53%, respectively, and S. aureus eradication rates of 94 and 40%, respectively. However, clinical results of individual clinical trials with mupirocin usually (8 of 11 studies) did not show mupirocin to be significantly better than vehicle, although overall cumulated clinical success rates of 94 and 71%, respectively, suggest mupirocin’s superiority. In particular, cumulated success rates in patients with infected eczema/atopic dermatitis were 92 and 58%, respectively, and in patients with infected wounds were 86 and 67%, respectively. However, in smaller numbers of patients with infected burns, ulcerated skin lesions or bites, no clear advantages can yet be ascribed to mupirocin over vehicle, with high success rates being achieved by both.

In a few studies, mupirocin has shown very good potential for use in the eradication of Staphylococcus aureus, including methicillin-resistant strains, from the anterior nares of carriers, with all patients in all studies showing rapid bacterial eradication and prevention of recolonisation for up to several months. Work is currently being undertaken to improve the acceptability of the vehicle in these patients.

Side Effects: Mupirocin has not been reported to cause systemic toxic effects. Local effects such as burning, stinging, itch and rash have been reported, but these occur in a low proportion of patients (less than 3%) which is no greater than with vehicle ointment, implicating the polyethylene glycol base as the probable causative factor.

Dosage and Administration: Mupirocin 2% ointment should be applied topically, directly to the site of superficial skin infection. The dosage regimen should be 2 or 3 times daily for 5 to 14 days in most patients, although longer application may be necessary in chronic or more severe infection.

Keywords

Minimal Inhibitory Concentration Skin Infection Eradication Rate Mupirocin Fusidic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© ADIS Press Limited 1986

Authors and Affiliations

  • Alan Ward
    • 1
  • Deborah M. Campoli-Richards
    • 1
  1. 1.ADIS Drug Information ServicesMairangi Bay, Auckland 10New Zealand

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