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January 2013 | Volume 12 | Issue 1 | Feature | 122 | Copyright © 2013

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Current and Future Trends in Topical Antimicrobials

INTRODUCTION

Topical antibiotics have a variety of dermatologic applications, including acne vulgaris, impetigo,1 and other secondarily infected dermatoses2 such as erythrasma,3 furunculosis,2,3 burns,4 and the prevention and treatment of surgical wound infections. Other indications include staphylococcal decolonization1,4 and prophylaxis against infection in traumatic lesions. A variety of microorganisms are implicated in skin infections and can complicate wound healing, 5 with Staphylococcus aureus,2,6 Streptococcus pyogenes, and Pseudomonas aeruginosa representing the 3 most common minor wound pathogens.6

Topical antimicrobial therapy is advantageous over oral regimens for several reasons. First, it provides high drug concentrations localized to the site of infection.2,4 Second, it minimizes systemic toxicity due to minimal, if any, absorption into circulation.7 Third, it reduces antimicrobial resistance selection among other bacteria in the body, which often results from systemic antibiotic administration.2,4 Finally, when used in the treatment of minor traumatic wounds, topical antimicrobials confer important benefits: infection prophylaxis, bacterial eradication, and enhanced wound healing times.6 Potential adverse effects include local allergic reaction to the drug or its vehicle, emergence of local resistance after prolonged use, and diminished efficacy in established infection due to poor skin penetration.2

Uncomplicated skin infections are responsible for approximately 200 million physician visits annually, with treatment costs estimated to be greater than $350 million per year.2 Importantly, dermatologists frequently create iatrogenic wounds when they employ diagnostic and therapeutic strategies such as biopsies, excisions, cryotherapy, and laser therapy.1 The success of such procedures involves the proper healing and avoidance of infection of these wounds; therefore, wound care after minor office procedures often includes treatment with a topical antibiotic.1,8 Yet the frequent use of topical antimicrobials after office procedures is not necessarily congruent with the literature. For example, studies that demonstrated that the infection rate for postoperative wounds is often less than 1.5%.9 In addition, other studies have shown that there is no statistical difference in infection rates between superficial wounds treated with topical antibiotics compared with those treated with topical petrolatum.9-13 With the risk of resistant strain emergence from antibiotic overuse, it is important for dermatologists to be knowledgeable about the antimicrobial spectrum of different topical antibiotics, cognizant of the indications for and against topical antibiotic prescription, and capable of educating their patients regarding appropriate antibiotic application.

OVER-THE-COUNTER TOPICAL ANTIBIOTICS

Bacitracin
Originally developed for systemic administration, nephrotoxicity limited bacitracin’s parenteral use,4 and it was formulated topically to be over the counter (OTC) since the 1970s. Bacitracin is a polypeptide antibiotic produced by Bacillus subtilis, and its mechanism of action involves inhibition of bacterial cell wall synthesis.3,4,14 It is active against staphylococci,4,15 S pyogenes,4,15 and other Gram-positive pathogens.4 Development of resistance is rare, but some S aureus resistance has been reported.15 This antibiotic is popular for topical treatment of minor infections and is advantageous because of its low toxicity profile and affordability.15 Nevertheless, the incidence of allergic contact dermatitis is on the rise,16 with bacitracin noted to be one of 12 most common causative agents.17

Neomycin
This aminoglycoside was introduced as a prescription antimicrobial in the 1950s and has been OTC since the 1970s.2 Produced by Streptomyces fradiae,3,4,15 neomycin inhibits bacterial protein synthesis and is active against staphylococci and many Gram -negative pathogens4,6 including Escherichia coli, Haemophilus influenza, Proteus, and Serratia.15 However, staphylococcal resistance to neomycin precludes its use as monotherapy for treatment of skin infections with this pathogen.6 The risk of allergic contact dermatitis to neomycin may also limit its use, with an estimated prevalence between 1% and 6%.4 In a cross-sectional study of more than 959 patients with allergic contact dermatitis of the hand, neomycin sulfate was one of the 12 most common causative agents.17 However, evidence suggests that intermittent use of neomycin is not associated with a high rate of sensitization.18

Polymyxin B
Like bacitracin and neomycin, this topical antimicrobial is available OTC,2 and it is isolated from Bacillus polymyxa.3,15 Its antimicrobial effects derive from its ability to increase permeability of the bacterial cell wall, thus disrupting intracellular osmolar integrity and inducing bacterial cell lysis.6 Polymyxin B is highly active against P aeruginosa6 and other Gram-negative bacteria.3,4 Its major utility is in the prevention and treatment of minor skin infections.15 Low-level resistance to this antimicrobial is rare, whereas high-level resistance can occur after repeated exposure to increasing doses.6

Triple Antibiotic Ointment (TAO)
This topical therapeutic was introduced 1956 for the prevention19 and treatment of common skin infections and is now available OTC. TAO contains the active ingredients bacitracin, neomycin, and polymyxin B.6 These 3 component antimicrobials provide a complementary and overlapping antibacterial spectrum,6 and TAO is active against the most common skin pathogens: meth-


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