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, including clindamycin, bind to the 23S subunit of the bacterial ribosome and suppress the early stages of protein synthesis. Clindamycin is primarily 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 the compound to clindamycin, which possesses 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 vitro, clindamycin inhibited the growth of all tested cultures of Propionibacterium acnes (MIC 0.4 mcg/mL). The level of free fatty acids on the skin surface declined from approximately 14% before treatment to 2% following application of clindamycin. Benzoyl peroxide exhibits mild keratolytic activity against comedones at all stages of development. It is an oxidising agent with bactericidal activity against Propionibacterium acnes, the microorganism implicated in the development of acne vulgaris. Benzoyl peroxide additionally exerts a sebostatic effect, counteracting the excessive sebum production associated with acne. Duac combines mild keratolytic and antibacterial properties, allowing it to act effectively against the inflammatory skin lesions 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, particularly when treating severe infections. The presence of benzoyl peroxide reduces the likelihood of clindamycin-resistant organisms emerging. Combining both active substances within a single preparation is advantageous and supports better patient adherence to therapy. Clinical efficacy and safety Of 1,318 patients with facial acne vulgaris involving both inflammatory and non-inflammatory lesions, enrolled in five double-blind, randomised clinical studies, 396 patients received Duac, 396 benzoyl peroxide, 349 clindamycin and 177 vehicle. Treatment was applied once daily for 11 weeks, with assessments and lesion counts performed at weeks 2, 5, 8 and 11. The mean percentage reduction in lesion count after 11 weeks of treatment is shown in the following table. Mean percentage reduction in lesion count 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 count compared with clindamycin or vehicle. Duac demonstrated a greater effect than benzoyl peroxide, although the difference did not reach statistical significance in the individual studies. For inflammatory lesions, Duac was significantly more effective than clindamycin alone in four of the five studies and than benzoyl peroxide alone in three of the five studies. For non-inflammatory lesions, Duac was significantly more effective than clindamycin in four of the five studies, with a trend toward greater efficacy compared with benzoyl peroxide alone. The physician's global assessment of overall improvement concluded that Duac was significantly more effective than either benzoyl peroxide alone or clindamycin alone in three of the five studies. An effect on inflammatory lesions was evident from week 2 of treatment. The effect on non-inflammatory lesions was more variable, with efficacy generally apparent after 2–5 weeks of treatment.