Topical antibiotics for acne accumulate in the follicle and have been postulated to work through antiinflammatory mechanisms and via antibacterial effects.60 These agents are best used in combination with BP (wash-off or leave-on), which increases efficacy and decreases the development of resistant bacterial strains. Monotherapy with topical antibiotics in the management of acne is not recommended because of the development of antibiotic resistance. Clindamycin 1% solution or gel is currently the preferred topical antibiotic for acne therapy.¹⁷³ Topical erythromycin in 2% concentration is available as a cream, gel, lotion, or pledget,^61,62 but has reduced efficacy in comparison with clindamycin because of resistance of cutaneous Staphylococci and P acnes.^60,63-66 Stable, fixed-combination agents are available with erythromycin 3%/BP 5%, clindamycin 1%/BP 5%, and clindamycin 1%/BP 3.75%.^67-69,174 Combination agents may enhance compliance with treatment regimens. Rare reports of diarrhea or Clostridium difficile–related colitis with clindamycin topically have appeared in the literature, but the risk appears low.⁶⁶ Tolerance of these agents is excellent; clindamycin alone is pregnancy category B.

Topical retinoids are vitamin A derivatives that are prescription agents with randomized, double-blind, placebo-controlled trials supporting their use for acne treatment.^70-72,175 Three active agents are available: tretinoin (0.025-0.1% in cream, gel, or microsphere gel vehicles), adapalene (0.1%, 0.3% cream, or 0.1% lotion^73,74), and tazarotene (0.05%, 0.1% cream, gel or foam). Each retinoid binds to a different set of retinoic acid receptors: tretinoin to alpha, beta, and gamma, and tazarotene and adapalene, selectively, to beta and gamma—thereby conferring slight differences in activity, tolerability, and efficacy. Retinoids are the core of topical therapy for acne because they are comedolytic, resolve the precursor microcomedone lesion, and are antiinflammatory.

These agents enhance any topical acne regimen and allow for maintenance of clearance after discontinuation of oral therapy. Retinoids are ideal for comedonal acne and, when used in combination with other agents, for all acne variants. Three topical agents are available that contain retinoids in combination with other products: adapalene 0.1%/BP 2.5%, approved for use in patients ≥9 years of age, and 2 agents with fixed combination clindamycin phosphate 1.2%/tretinoin 0.025% gel, approved for patients ≥12 years of age.75,76,176

Retinoid use may be limited by side effects, including dryness, peeling, erythema, and irritation, which can be mitigated by reduced frequency of application.¹⁷⁷ Given any single agent, higher concentrations may be more efficacious, but with greater side effects.^70,74,77 Some formulations of tretinoin (primarily generic products) are not photostable and should be applied in the evening. Tretinoin also may be oxidized and inactivated by the coadministration of BP. It is recommended that the 2 agents be applied at different times. Tretinoin microsphere formulation, adapalene, and tazarotene do not have similar restrictions. Topical retinoids have been associated with an increased risk of photosensitivity; concurrent daily sunscreen can be used to reduce the risk of sunburn.

There are several head-to-head studies with retinoid products. Some support greater efficacy of tazarotene over adapalene and tretinoin, and adapalene over tretinoin, but the concentrations and formulations used were varied.^73,78-80 Data suggest that adapalene is better tolerated than multiple concentrations of tretinoin, but this is based on older formulations.⁸¹ Overall, the limitations of the existing studies prohibit direct efficacy comparisons of topical retinoids.

Tretinoin and adapalene are pregnancy category C, while tazarotene is category X; therefore, patients should be counseled on these pregnancy risks when starting a retinoid or if a woman patient desires pregnancy.

The therapy of acne in children <12 years of age with products approved by the FDA has expanded. Fixed combination BP 2.5%/adapalene 1% gel is approved for patients ≥9 years of age, and tretinoin 0.05% micronized tretinoin gel for patients ≥10 years of age. All other retinoids are approved by the FDA for patients ≥12 years of age. Current data show that retinoids in younger patients are effective and are not associated with increased irritation or risk.

Azelaic acid 20% is mildly effective as a comedolytic, antibacterial, and antiinflammatory agent. The agent has use in patients with sensitive skin or of Fitzpatrick skin types IV or greater because of the lightening effect of the product on dyspigmentation.^82,83,178 Azelaic acid is category B in pregnancy.

The sulfone agent, dapsone 5% gel, is available as a twice-daily agent for the therapy of AV. In clinical trials, topical dapsone showed modest to moderate efficacy, primarily in the reduction of inflammatory lesions.^84,85 Combination with topical retinoids may be indicated if comedonal components are present. The mechanism of action is poorly understood, and its ability to kill P acnes has been poorly studied. It is generally thought to work as an antiinflammatory agent. The benefit in women seems to exceed the benefit in male and adolescent patients.^86,179 Topical dapsone may be oxidized by the coapplication of BP, causing orange-brown coloration of the skin which can be brushed or washed off. Topical dapsone 5% gel is pregnancy category C and has efficacy and safety data down to patients 12 years of age. Glucose-6-phosphate dehydrogenase testing is not required before starting topical dapsone.

Salicylic acid is a comedolytic agent that is available over the counter in 0.5% to 2% strengths for the therapy of AV. Both wash-off and leave-on preparations are well tolerated. Clinical trials demonstrating the efficacy of salicylic acid in acne are limited.^87,180

Although sulfur and resorcinol have been used for many years in the treatment of acne, evidence from peer-reviewed literature supporting their efficacy is lacking.181 Aluminum chloride possesses antibacterial activity and, therefore, has been investigated in the treatment acne. Of 2 peer-reviewed studies, 1 found benefit¹⁸² and 1 did not.¹⁸³ Topical zinc alone is ineffective.^184-186 There is some evidence to suggest the efficacy of sodium sulfacetamide.^187-189 Topical niacinamide (nicotinomide) 2% to 4% gel is available over the counter. The limited studies available compare its efficacy to topical clindamycin 1% gel.^190,191

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