Clindamycin

Pharmacotherapeutic group: Clindamycin, combinations. ATC code: D10AF51 Clindamycin is a lincosamide antibiotic with antibacterial activity against Gram-positive aerobes and a broad spectrum of anaerobic bacteria. Lincosamides, to which clindamycin belongs, bind to the 23S subunit of the bacterial ribosome and inhibit the early stages of protein synthesis. Clindamycin is predominantly bacteriostatic, although at higher concentrations it may act as a latent bactericidal agent against susceptible strains. Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts it to clindamycin, which exerts antibacterial activity. Clinical trials in patients with acne have shown that this activity of clindamycin within acne comedones is sufficiently effective against most strains of Propionibacterium acnes. In in vitro testing, clindamycin inhibited the growth of all Propionibacterium acnes cultures tested (MIC 0.4 mcg/ml). The level of free fatty acids on the skin surface decreased from approximately 14% to 2% following clindamycin application. Benzoyl peroxide exhibits mild keratolytic activity against comedones at all stages of their development. It is an oxidising agent with bactericidal activity against Propionibacterium acnes, the microorganism implicated in the pathogenesis of acne vulgaris. Benzoyl peroxide also has a sebostatic effect, counteracting the excessive sebum production associated with acne. Duac combines mild keratolytic and antibacterial properties that enable it to act effectively, particularly against the inflammatory skin lesions characteristic of mild to moderate acne vulgaris. The prevalence of acquired resistance may vary geographically and over time for selected organisms. Local resistance data are desirable, especially when treating severe infections. The presence of benzoyl peroxide reduces the likelihood of emergence of clindamycin-resistant organisms. Combining both active substances in a single product is advantageous and supports better patient adherence to therapy. Clinical efficacy and safety Of 1,318 patients with facial acne vulgaris presenting with both inflammatory and non-inflammatory skin lesions enrolled in five randomised, double-blind clinical studies, 396 received Duac, 396 received benzoyl peroxide, 349 received clindamycin and 177 received vehicle. Treatment was applied once daily for 11 weeks, and patients were assessed with lesion counts at 2, 5, 8 and 11 weeks after initiation of treatment. The mean percentage reduction in skin lesion counts after 11 weeks of treatment is shown in the following table. Mean percentage reduction in lesion counts from baseline at 11 weeks Study 150 (n = 120) Study 151 (n = 273) Study 152 (n = 280) Study 156 (n = 287) Study 158* (n = 358) Inflammatory lesions Duac 65 56 42 57 52 Benzoyl peroxide 36 37 32 57 41 Clindamycin 34 30 38 49 33 Vehicle 19 -0.4 29 - 29 Non-inflammatory lesions Duac 27 37 24 39 25 Benzoyl peroxide 12 30 16 29 23 Clindamycin -4 13 11 18 17 Vehicle -9 -5 17 - -7 Total lesions (inflammatory and non-inflammatory) Duac 41 45 31 50 41 Benzoyl peroxide 20 35 23 43 34 Clindamycin 11 22 22 33 26 Vehicle 1 -1 22 - 16 * Pivotal study Statistically significant differences are shown in bold In all five studies, Duac produced a significant reduction in total lesion counts compared with clindamycin or vehicle. Duac showed greater efficacy than benzoyl peroxide, although the observed difference did not reach statistical significance in the individual studies. For inflammatory skin lesions, Duac was significantly more effective than clindamycin alone in four of five studies and than benzoyl peroxide alone in three of five studies. For non-inflammatory lesions, Duac was significantly more effective than clindamycin in four of five studies, with a trend towards greater efficacy compared with benzoyl peroxide alone. The global improvement in patient status was rated by the investigator, who concluded that Duac was significantly more effective than benzoyl peroxide alone and than clindamycin alone in three of five studies. An effect on inflammatory lesions was apparent from week 2 of treatment. The effect on non-inflammatory lesions was more variable, with efficacy typically evident after 2–5 weeks of treatment.