have been shown to have greater adherence to regimens with fewer steps.22 For this reason, fixed-dose combination topical drugs have become popular options in treating acne rather than applying each of the monotherapies twice daily. Combinations include BPO-antibiotics, BPO-topical retinoids, and topical retinoids - topical antibiotics in various generic and branded formulations.
Benzoyl Peroxide
Benzoyl peroxide has at the same time anti-microbial, anti-inflammatory, and keratolytic properties. It is a recommended component of almost all combination regimens for treating acne.21,23 BPO is directly toxic to P. acnes, and to date there are no reports of P. acnes resistance.24 BPO is thought to work by inhibiting the metabolism of P. acnes’ interference with protein synthesis and mitochondrial function, and lead to DNA damage.25 It is commonly used alongside topical antibiotics to prevent the development of bacterial resistance, and acne improvement has been noted after BPO was given to patients with previously known P. acnes resistance.26 By killing P. acnes and preventing its subsequent production of pro-inflammatory mediators, BPO is indirectly anti-inflammatory.21 Moreover, BPO has keratolytic properties. Statistically higher concentrations of corneocytes have been shown to be removed by tape-strip analysis after application of BPO 2% cream compared with vehicle cream or untreated skin.27.
Benzoyl peroxide has at the same time anti-microbial, anti-inflammatory, and keratolytic properties. It is a recommended component of almost all combination regimens for treating acne.21,23 BPO is directly toxic to P. acnes, and to date there are no reports of P. acnes resistance.24 BPO is thought to work by inhibiting the metabolism of P. acnes’ interference with protein synthesis and mitochondrial function, and lead to DNA damage.25 It is commonly used alongside topical antibiotics to prevent the development of bacterial resistance, and acne improvement has been noted after BPO was given to patients with previously known P. acnes resistance.26 By killing P. acnes and preventing its subsequent production of pro-inflammatory mediators, BPO is indirectly anti-inflammatory.21 Moreover, BPO has keratolytic properties. Statistically higher concentrations of corneocytes have been shown to be removed by tape-strip analysis after application of BPO 2% cream compared with vehicle cream or untreated skin.27.
The most common adverse events (AEs) that patients associate with BPO are concentration-dependent irritant dermatitis. True allergic contact dermatitis is quite rare.28,29 In fact, studies have shown that not only are lower concentrations of BPO less irritating than higher concentrations, but they also demonstrate similar efficacy to higher concentrations.30 In one study, twice-daily application of BPO 2.5% resulted in a 97% and 99% reduction in P. acnes counts after 1 week and 2 weeks respectively.31 While products are vehicle- and formulation-dependent and generalizations cannot be made blindly, in general lower BPO concentrations may be preferred because they cause less potential skin irritation.
Topical Antibiotics
Antibiotics have both anti-microbial and anti-inflammatory effects on the skin. They reduce the levels of P. acnes bacteria within the sebaceous follicles. Some (eg, erythromycin and tetracyclines) also have direct anti-inflammatory properties, reducing pro-inflammatory chemotactic factors and lipase levels at concentrations lower than the mean inhibitory concentrations needed for P. acnes killing.32 Lipophilic antibiotics are considered best for acne because they can most easily penetrate the lipid-filled, sebaceous environment. These include macrolides (eg, erythromycin), clindamycin, tetracyclines (eg, doxycycline, minocycline), and trimethoprim.33
Antibiotics have both anti-microbial and anti-inflammatory effects on the skin. They reduce the levels of P. acnes bacteria within the sebaceous follicles. Some (eg, erythromycin and tetracyclines) also have direct anti-inflammatory properties, reducing pro-inflammatory chemotactic factors and lipase levels at concentrations lower than the mean inhibitory concentrations needed for P. acnes killing.32 Lipophilic antibiotics are considered best for acne because they can most easily penetrate the lipid-filled, sebaceous environment. These include macrolides (eg, erythromycin), clindamycin, tetracyclines (eg, doxycycline, minocycline), and trimethoprim.33
Clindamycin and erythromycin are the 2 most commonly used topical antibiotics in the United States for the treatment of acne.34 Topical erythromycin has largely fallen out of favor with most experts because of high levels of resistance by P. acnes.35 Clindamycin is widely used as an individual agent combined with a separate BPO-containing preparation or as an ingredient in one of many fixed-dose BPO/clindamycin combination products.
Besides being antimicrobial, clindamycin’s anti-inflammatory properties play an important role in its therapeutic effect. Clindamycin has been shown to lower P. acnes-related inflammatory factors, decreasing lipase production and the subsequent release of free fatty acids. In addition, it has been shown to inhibit leukocyte chemotaxis, reducing perifollicular inflammation. Clindamycin has also been shown to reduce levels of pro-inflammatory cytokines IL1-β, IL-6, INF-γ, TNF-α, and GM-CSF.36,37
While tetracyclines are used orally, there are no topical versions currently available in the US. Minocycline, however, has been successfully stabilized in a topical foam formulation and is currently in development stages. This drug will be reviewed in a subsequent section.
With the growing awareness of bacterial resistance to antibiotics, monotherapy with topical (or oral) antibiotics is not recommended for the treatment of acne.38 The first reports of bacterial resistance to topical clindamycin came in the 1970’s and were the result of mutations in 23S ribosomal RNA, conferring cross-resistance to both erythromycin and clindamycin.39 Resistance has been demonstrated in clinical studies. In one trial, clindamycin as monotherapy for the treatment of acne for 16 weeks resulted in P. acnes counts increasing by more than 1600% compared with baseline. This effect was blocked with the addition of BPO.40 Current guidelines recommend the concurrent use of BPO with topical antibiotics to reduce the risk of developing resistance.26
Topical Retinoids
Retinoids are a class of drugs similar in structure to Vitamin A. Vitamin A interacts with nuclear receptors to stimulate processes related to cell growth and differentiation. Three topical retinoids are available by prescription in the US: tretinoin, tazarotene, and adapalene (ADA).41 Collectively these drugs
