For the last 40 years, benzoyl peroxide has been a common prescribed agent for acne (Burkhart, Butcher, Burkhart, & Lehmann, 2000). In addition to it acting as a bactericidal agent against P. acnes (Cove & Holland, 1983), it acts as a mild peeling agent, has comedolytic activity, and decreases fatty acid and lipid levels (Physicians' Desk Reference, 2001). Benzoyl peroxide has no association with causing any P. acnes resistance (Gollnick & Schramm, 1998). In the United States, benzoyl peroxide is available from 2.5% to 10% concentrations. In a study involving 153 patients with mild to moderately severe acne, the 2.5% preparation of benzoyl peroxide was equivalent to the 5% and 10% concentrations at decreasing the number of inflammatory acne lesions with fewer side effects (Mills, Kligman, Pochi, & Comite, 1986).
Clindamycin and erythromycin inhibit protein synthesis by irreversibly binding to the ribosomal 50S subunit of P. acnes (Physician's Desk Reference, 2001). Whereas erythromycin is bactericidal, clindamycin is both bactericidal and bacteriostatic (Wolverton, 2001). Clindamycin is available as a 1% gel, 1% lotion, or 1% solution and erythromycin as either a 2% or 3% concentration in various vehicles. Clindamycin and erythromycin are both superior to placebo at decreasing acne lesion counts. Comparison of erythromycin 2% gel with clindamycin 1% solution in a 12-week, randomized, parallel-group study found both to be equally efficacious (Leyden, Hickman, Jarratt, Stewart, & Levy, 1987).
Generally, the acquisition of antibiotic-resistant genes by bacteria occurs when genetic elements, such as transposons and plasmids, are transferred to other strains or species within the resident skin flora. Some bacteria may be innately resistant to certain antibiotics. However, with erythromycin, clindamycin, and tetracyclines, the rate of resistance is associated with point mutations in rRNA (Ross et al., 2001). Mutations in the 23SrRNA component of an E. coli equivalent nucleotide bases give varying degrees of resistance to erythromycin and clindamycin. For instance, mutations at site E. coli equivalent nucleotide base 2057 create low levels of resistance to erythromycin and no resistance to clindamycin. In contrast, mutations at site E. coli equivalent nucleotide base 2058 create varying degrees of resistance to both erythromycin and clindamycin, whereas mutations at site E. coli equivalent nucleotide base 2059 create high levels of resistance to erythromycin and low levels to clindamycin (Coates et al., 2002). Therefore, as a result of these mutations, most resistance of P. acnes to erythromycin is cross-resistant to clindamycin (Coates et al., 2002). In one study, patients treated with topical clindamycin had an increase in erythromycin-resistant propionibacteria in 64% of patients who had previously been treated with oral erythromycin compared to only 20% of patients with no prior treatment (Eady, Cove, Holland, & Cunliffe, 1989).
Azelaic acid is a naturally occurring dicarboxylic acid found in wheat, rye, and barley (Usatine & Quan, 2000). In addition to being bacteriostatic and bactericidal, it normalizes follicular keratination, is comedolytic, and has activity against hypermelanosis (Wolverton, 2001). It is available in the United States as a 20% concentration. Similar to benzoyl peroxide, azelaic acid has no potential to induce bacterial resistance (Gollnick & Schramm, 1998).
Sodium sulfacetamide is effective against P. acnes. It is commonly combined with sulfur in acne preparations. Sodium sulfacetamide acts as a competitive antagonist to para-aminobenzoic acid (PABA), an essential component for bacterial growth. Sulfur, in addition to acting as a keratolytic, inhibits growth of P. acnes and the development of free fatty acids (Physicians' Desk Reference, 2001). Although P. acnes resistance to sodium sulfacetamide has not been recognized in the literature, resistance to numerous staphylococcal isolates with topical sodium sulfacetamide has been identified in the treatment of conjunctivitis (CDCUpdate, 2002).
Combination Topical Therapy
One approach at decreasing antibiotic-resistant bacteria is to combine benzoyl peroxide with other topical agents with complementary but distinct mechanisms of antibacterial action, such as clindamycin or erythromycin. Studies have demonstrated that a 5% benzoyl peroxide/1% clindamycin combination topical gel is superior to clindamycin monotherapy at significantly decreasing the total P. acnes count and P. acnes resistance (Cunliffe, Holland, Bojar, & Levy, 2002; Leyden, 2001). One study identified a 5% benzyl peroxide/3% erythromycin combination topical gel as being more effective than erythromycin alone, resulting in a 3 log decrease in total P. acnes and a significant reduction in erythromycin-resistant strains with the combination topical gel, compared to only a 1.5 log decrease in total P. acnesand no reduction in erythromycin-resistant strains with erythromycin monotherapy (Eady et al., 1996). Although not significant, one study demonstrated a trend for greater efficacy with a benzoyl peroxide/clindamycin preparation compared to a benzoyl peroxide /erythromycin combination topical gel (Leyden et al., 2001).
Dermatology Nursing. 2003;15(4) © 2003 Jannetti Publications, Inc.
Cite this: Antibiotic Resistance of Propionibacterium acnes in Acne Vulgaris - Medscape - Aug 01, 2003.