Treating Acne Vulgaris: Systemic, Local and Combination Therapy

Laura J Savage; Alison M Layton

Disclosures

Expert Rev Clin Pharmacol. 2010;13(4):563-580. 

In This Article

Topical Antibiotics

Topical antibiotics are beneficial for reducing inflammatory lesions through diminution of skin surface and follicular P. acnes.[44] They exert their direct anti-inflammatory actions via an antioxidant effect on leukocyte chemotaxis and suppress proinflammatory free fatty acids and surface lipids.[45] Topical antibiotics also have some effect on noninflamed lesions by reducing perifollicular lymphocytes, which are involved in comedogenesis.[46]

Topical antibiotics used in the treatment of acne include clindamycin, erythromycin and tetracycline. They are available in concentrations of 1–4% with a cream or lotion base. Topical clindamycin has been compared with topical erythromycin in mild-to-severe acne, with no overall differences in clinical outcome.[47–49] However, tetracycline has been shown to be the least effective topical antibiotic with less overall improvement in severity when compared with topical clindamycin.[50,51]

Topical erythromycin and clindamycin have been demonstrated in clinical trials to be as effective as BPO,[52] and combinations of 3% erythromycin with zinc or 5% BPO are shown to be superior to single therapies.[47,53–57] Owing to the emergence of antibiotic-resistant P. acnes, use of topical antibiotics as monotherapy is now not recommended and guidelines suggest that BPO or zinc should be combined in any topical antibiotic preparation.[13,14]

Several studies have examined the use of oral versus topical antibiotics in the management of acne. Unfortunately, the duration of many RCTs has been insufficient to account for the delay in onset of action of oral antibiotics, hence affording bias to the topical agent. Eady et al. analyzed 144 clinical trials of topical antibiotic therapy and rejected over 50% owing to poor study design.[52] Adequate data could not be drawn from the remaining studies because of the different protocols used. One large RCT demonstrated that topical Benzamycin® (Dermik-Laboratories Inc., Sanofi Aventis, NJ, USA; combination product: 3% erythromycin and 5% BPO) was superior in efficacy to oral tetracycline and minocycline.[32]

Increasing worldwide emergence of antibacterial resistance to P. acnes is an important consideration. Resistance is most problematic with topical erythromycin, with 47% patients in UK primary care harboring resistant strains of P. acnes, closely followed by clindamycin (41%) and tetracycline (18%).[32] With topical antibiotic administration, resistance develops in both targeted and nontargeted bacteria and the resident flora retain a memory for resistant variants long after antibiotics are discontinued. Mills et al. demonstrated that erythromycin-resistant coagulase-negative staphylococci on the face increased from 87 to 98% following a 12-week administration of topical 2% erythromycin gel as compared with double-blind controls who were randomized to use the antibiotic vehicle only.[58] In addition, the density of resistant organisms increased significantly, with the majority of resistant isolates demonstrating high-level resistance. Similar patterns of both prevalence and density were also observed in nontargeted bacteria isolated from untreated skin on the back and in the nares.[58]

Treatment failure may be attributed to resistance in some cases. There has been some correlation demonstrated between poor response and the presence of antibiotic-resistant P. acnes.[32,59,60] However, the association between response and colonization with antibiotic-resistant strains is complex and if a specific antibiotic-resistant strain of P. acnes is reported microbiologically, it does not necessarily transpire that the acne will be clinically resistant to this antibiotic. If the antibiotic concentration at the relevant skin site is equal or greater than the minimal inhibitory concentration of that strain of P. acnes, the patient will be clinically responsive.[15] Topical antibiotics achieve some efficacy via anti-inflammatory as well as antibacterial actions, and the former can therefore offset problems with antibiotic resistance.[61] It is now recommended that topical antibiotics should not be used as monotherapy and should only be continued until such a time as visible clinical improvement ceases.[14]

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