The Role of Benzoyl Peroxide in the New Treatment Paradigm for Acne

June 2013 | Volume 12 | Issue 6 | Supplement Individual Articles | 73 | Copyright © June 2013

Leon H. Kircik MD

Mount Sinai Medical Center, New York, NY
Indiana University School of Medicine, Indianapolis, IN
Physicians Skin Care, PLLC, Louisville, KY

Although few randomized controlled trials have studied the clinical efficacy of oral antibiotics in acne, tetracycline and erythromycin have been shown to reduce inflammatory lesions by 64% and 67%, respectively.2 Other comparative studies have typically shown few or no important differences in clinical efficacy between the oral antibiotics. A recent Cochrane meta-analysis concluded that minocycline is effective for moderate acne, but data are insufficient to compare its efficacy to that of other acne therapies.22
Tetracyclines, macrolides, and trimethoprim-sulfamethoxazole can be used to treat moderate to severe acne.14,19 Whereas long-term therapy is commonly used, short courses may be effective and may reduce the risk for development of antibiotic resistance.15
Alternatively, topical BP is a relatively inexpensive agent that is proven bactericidal against P acnes with no known risk of resistance.

The Reemergence of Benzoyl Peroxide

Lincosamide antibiotics such as clindamycin and macrolide antibiotics such as erythromycin have a similar method of action, inhibiting the protein synthesis of P acnes by attaching to the 50S subunit of the bacterial ribosome.23 In contrast, BP’s mechanism of action does not involve bacterial ribosomal synthesis. Benzoyl peroxide is a potent oxidizing agent. By generating reactive oxygen species that physically interact with constituents of the bacteria, it exerts a bactericidal effect.
Combining BP with a topical antibiotic in a stable formulation has been proven in clinical trials to reduce total P acnes count by 99.7% after 1 week of therapy, eliminating both susceptible and resistant strains of P acnes.24 Clinically, combination therapy with BP and a topical antibiotic has been proven to prevent the emergence of resistant strains of P acnes. For this reason, the current clinical recommendation is to include BP in topical anti-acne regimens to preclude the development of antibiotic resistance.15
Benzoyl peroxide’s efficacy as a monotherapy was traditionally considered to be limited; however, the agent is readily used in fixed-dose combinations with antibiotics or topical retinoids, providing documented benefit.25-27 For example, the fixed-dose combination of adapalene 0.1%/BP 2.5% was associated with early improvement in quality of life and high levels of treatment satisfaction among treated patients compared with control subjects. 26 In clinical trials, adapalene/BP combination gel showed a significantly higher success rate (P<.006 or P=.006) and a greater percentage reduction in all acne lesion counts (P<.017 or P=.017) compared with adapalene or BP monotherapy.27
We are also now noticing BP’s benefits as monotherapy in the treatment of acne. The effect of BP on P acnes is rapid. After just 2 days of treatment with BP 5%, an almost 2-log10 decrease in P acnes counts was observed. No further decrease was observed at subsequent times.28
Lee et al found that P acnes synthesizes coproporphyrin III, producing the well-known orange-red follicular fluorescence under 385-nm to 415-nm light.29 Benzoyl peroxide’s activity against P acnes was demonstrated in an elegant study using 385-nm to 415-nm light fluorescence.30 When subjects with acne were treated with BP 10%, P acnes counts were significantly lower compared with untreated controls both at day 3 (P=.007) and at day 7 (P=.0001). Researchers also cultured P acnes from subjects and showed that a decrease in cultured P acnes density in the treated group paralleled the dramatic decrease in porphyrin fluorescence. Of note, documented recolonization of P acnes 10 days after stopping BP was matched by a corresponding reappearance of porphyrins.30 Because the intensity of fluorescence is proportional to the density of P acnes and decreases with BP treatment, digital fluorescence photography was selected as a reliable, noninvasive method to estimate the suppressive effects of BP 10% on P acnes.30
Thirty healthy adults with high facial P acnes counts (>10 colony-forming units/cm2 from the forehead) were recruited for a 4-week, single-center, open-label study.31The study sought to assess the presence of P acnes subpopulations resistant to erythromycin, tetracycline, and clindamycin before and throughout the course of treatment with the BP 2.5% and adapalene 0.1% fixed-dose combination. Subjects were instructed to apply adapalene 0.1%/BP 2.5% gel to the forehead once daily for 4 weeks. Cultures were taken at screening, baseline, week 2, and week 4. P acnes counts were high at baseline but reduced significantly by week 4 (Table 2.) Total P acnes were reduced by a mean 80% at week 2 and 93% at week 4. Erythromycin-resistant strains were reduced by 89% and 97%, clindamycin-resistant strains by 82% and 92%, tetracycline-resistant strains by 79% and 92%, minocycline-resistant strains by 85% and 97%, and doxycycline-resistant strains by 67% and 88%, respectively at week 2 and week 4. The authors acknowledge that their study was limited in scope; however, results demonstrate that the fixed-dose combination gel containing adapalene 0.1% and BP 2.5% effectively inhibited both antibiotic-susceptible and antibiotic-resistant P acnes.31
table 2