Overview of New Therapeutic Developments for Acne

Anja Thielitz; Harald Gollnick


April 13, 2009

In This Article

Topical Antimicrobials

Topical antimicrobials are an essential part of the therapeutic armamentarium for mild-to-moderate acne vulgaris and represent an alternative for patients who cannot take systemic antibiotics.

Topical antibiotics are used most commonly but should be administered in combination with benzoyl peroxide (BPO), an approach that also reduces the emergence of strains of P. acnes that are resistant or less sensitive to antibiotics. Topical antibiotics, such as clindamycin, erythromycin and tetracycline, are bacteriostatic for P. acnes and have also been demonstrated to have anti-inflammatory activities through inhibition of lipase production by P. acnes or inhibition of leukocyte chemotaxis.[8,9] In contrast to erythromycin, clinical efficacy of clindamycin did not decrease over time,[10] although the resistance of P. acnes to clindamycin increased and crossresistance to erythromycin is emerging. These data, together with the observation that clindamycin, to some extent, reduces comedones and microcomedones,[11] point to further para-antibiotic mechanisms of clindamycin, which deserve further investigation.

Clindamycin is used mainly as clindamycin phosphate and is available in various vehicles. A new foam formulation of clindamycin phosphate 1% demonstrated superior clinical efficacy and penetration compared with a clindamycin gel preparation, although systemic absorption was comparably low with both vehicles.[12]

Benzoyl peroxide is a nonantibiotic antimicrobial agent with bactericidal effects against P. acnes and, thus far, has not been detected to induce bacterial resistance. In addition, BPO has mild comedolytic but, as yet, no proven anticomedogenic effects on microcomedones. The drawback of the substance is its irritative potential, which has been reduced by a new microsponge delivery system allowing for a gradual release of BPO over time.[13]

Topical antibiotics should generally not be used as monotherapy and not for extended periods beyond 3 months. The combination of topical and systemic antibiotics, especially substances with distinct modes of action, should be avoided in order to prevent the development of multiresistant bacterial strains.[6,8]

Clindamycin and BPO Combination

Benzoyl peroxide is a lipophilic molecule able to penetrate the pilosebacous follicle, where it propagates free radicals to oxidize proteins in the bacterial cell membrane. The BPO radicals are increased markedly when used in combination with chemical structures that contain a tertiary amine within their structure, such as clindamycin and erythromycin, which would explain a real biologic synergism[14] in addition to complementary effects on pathogenetic factors of acne. Currently, two fixed-combination products of clindamycin 1% and BPO 5% are available (Duac®, Stiefel Laboratories, FL, USA, and BenzaClin®, SanofiAventis, France).

In five randomized, double-blind clinical studies of 1319 patients, Duac applied once daily for 11 weeks was significantly more effective than vehicle, BPO and clindamycin in the treatment of inflammatory lesions of moderate-to-moderately severe facial acne vulgaris in three out of the five studies.[15,93] In two well-controlled clinical studies of 758 patients, BenzaClin applied twice daily for 10 weeks was significantly more effective than vehicle in the treatment of moderate-to-moderately severe facial acne vulgaris, and the combination group showed greater overall improvement than the BPO, clindamycin and vehicle groups, as rated by the investigator.[16] A study published very recently investigated the effect of a clindamycin phosphate 1.2%/BPO 2.5% aqueous gel in 2813 patients with moderate-to-severe acne vulgaris and demonstrated superior efficacy of the combination compared with the individual active ingredients in inflammatory and noninflammatory lesion counts and acne severity, while maintaining a highly favorable safety profile.[17] In comparative short-term trials, clindamycin/BPO combination products showed a faster onset of action and better tolerability than erythromycin/zinc acetate or the monad adapalene.[18,19] Furthermore, the clindamycin/BPO products have been shown to be more effective and well tolerated when used in combination with retinoids.[19,20]


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