S. Skotnicki-Grant, MD, FRCPC

Divisions of Dermatology and Occupational Health, University of Toronto, Toronto, ON, Canada, Bay Dermatology Centre, Toronto, ON, Canada


Acne vulgaris is a multifactorial disease characterized by different types of lesions at various stages of development. Several obstacles encountered in the treatment of acne include irritation resulting from topical medications and the emergence of bacterial resistance to both topical and oral antibiotics. Over the last 20 years, the number of topical agents for the treatment of acne has been enriched. Advances in vehicle technology have produced improvements in efficacy and local tolerance. Our increased knowledge of acne pathogenesis has also led to therapeutic advances, such as the combined use of benzoyl peroxide (BPO) with topical or oral antibiotics, in order to reduce the potential for bacterial resistance.

Topical Acne Agents

  • BPO
  • Retinoid
    • Tretinoin
    • Adapalene
    • Tazarotene
    • Isotretinoin
  • Topical antibiotics
    • Clindamycin
    • Erythromycin
    • Sulfacetamide
  • Combination products
    • Retinoid with erythromycin
    • BPO with erythromycin
    • BPO with clindamycin

Retinoids for Initial/ Maintenance Therapy

Retinoids are pivotal for treatment in the early stages of acne, as well as for maintenance therapy, with both anti-comedonal and anti-inflammatory activity.

  • Topical retinoids can be used for all types and grades of acne, either initially or early in the therapy.
  • Topical retinoids are effective as monotherapy in pure comedonal acne.
  • Topical retinoids act by down-regulating TLR2 and CD14 messenger RNA, which reduces their cell surface expression, and results in anti-inflammatory activity.1
  • Several studies have shown that retinoids can enhance the effects of topical antibiotic-BPO combination creams.2 This may be because retinoids can improve the penetration of other topical agents.
  • Maintenance therapy or long-term use of retinoids may help to prevent the re-emergence of micro-comedones.
  • Maintenance therapy with retinoids may diminish the need for chronic antibiotic use, especially oral antibiotics. This, in turn, may lead to decreased bacterial resistance associated with both oral and topical long-term antibiotic use.

Topical Acne Agents and Bacterial Resistance

  • Topical antibiotic agents should not be used as monotherapy.
  • The combination of BPO with a topical antibiotic can result in a greater improvement in efficacy than monotherapy with either agent alone.
  • The addition of BPO to all long-term oral or topical antibiotic treatment has been shown to help suppress the emergence of antibiotic-resistant bacteria.
  • BPO may also reduce the further development of resistant strains that are already present.
    • For this reason, most new topical antibiotic acne agents include BPO.
  • Retinoids, although recommended in all forms of acne, have no apparent activity in preventing antibiotic resistance when used in combination with an antibiotic.

Advances in Topical Acne Formulations

Advances in topical agents have:

  • reduced the potential for irritation from tretinoin, due to the microsphere technology and novel pump dispenser.
  • permitted the use of microsphere tretinoin and adapalene in the morning, or directly before or after BPO application.
  • enabled the quick application of microsphere retinoids after facial washing.
  • reduced the irritation from clindamycin 1% plus BPO 5% alone, or in combination with a retinoid, because of the increase in humectants and emollients in the clindamycin/ BPO formulation.
  • decreased the emergence of bacterial resistance due to the addition of BPO to topical antibiotic agents, and the use of BPO with long-term oral antibiotics.

Vehicle Technology in Topical Acne Agents

  • Many new topical acne formulations have aqueous-based gel vehicle delivery systems that do not contain alcohol; they are suitable for use in all skin types.
  • It is known that topical acne agents cause cutaneous irritation related in part to impaired epidermal barrier function.3
  • The use of gentle cleansers and moisturizers has been shown to reduce this cutaneous irritation.4
  • The addition of vehicle components, such as humectants and emollients, to topical acne agents serves as a more natural approach to reducing epidermal barrier impairment and increasing skin moisturization.
  • The clindamycin 1%/ BPO 5% and the tretinoin microsphere gel formulations include both glycerin (a humectant) and dimethicone (an occlusive emollient).
  • Dimethicone’s occlusive properties result in less greasiness for enhanced cosmetic acceptability.

Tretinoin Microsphere Technology and Pump Delivery Systems

Tretinoin has been formulated with a patented microsphere delivery system and a novel pump bottle design, which, according to the manufacturer, allows for proper dosage and clean dispensing of the active agent. Clinical trials have shown:

  • lower levels of irritation due to the slow release of tretinoin from the microspheres into the epidermis.1,5
    • Reduced irritation may increase tolerability and patient adherence.
    • This is a less irritating water-based gel formulation that contains no alcohol and may be applied to the face immediately after washing with no waiting period.
  • the microsphere technology leads to greater photostability of the tretinoin and allows for morning use, if necessary.6
    • Retinoids formulated in a conventional gel or cream vehicle are unstable in the presence of ultraviolet light or BPO.1
    • Adapalene is also photostable and may be applied immediately before or after a BPO containing product.7
  • that controlled dispensing with this delivery system can avoid the overuse of tretinoin, thus reducing irritation and increasing treatment adherence.1
    • The dual chambered pump dispenser releases the correct pea-sized amount for full face application and may help to maintain the optimal dosing level.

Combination Therapy

  • Because the typical clinical presentation of acne vulgaris exhibits lesions at different stages, employing a combination approach that utilizes multiple agents to produce additive or synergistic benefits is logical.
  • Studies have shown that the topical combination of retinoids and antimicrobial agents expedites clinical response.2 This may be due to enhanced penetration of agents by the retinoids.
  • Retinoids, as discussed, can be prescribed as initial therapy. If inflammatory lesions are present, the addition of a BPO alone, or in combination with a topical or oral antibiotic, should be the next step.
  • A study showed that the combined use of a clindamycin 1%/ BPO 5% formulation with a 0.04% tretinoin microsphere gel, can result in good resolution of post-inflammatory hyperpigmentation in ethnic skin, i.e., individuals of colour.8


The multifactorial nature of acne vulgaris often requires a combination of topical and/or oral agents for successful management. Common challenges of this multipronged approach include the potential development of skin irritation, which results in nonadherence, as well as concern over bacterial resistance. Recent advances in topical acne agents offer simpler dosing regimes that can promote patient adherence. Furthermore, the cumulative benefits of these advances may lead to improved therapeutic outcomes and overall increase in quality of life.


  • Cutis 80(2):152-7 (2007 Aug).
  • Kircik L. Cutis 80(1 Suppl):10-4 (2007 Jul).
  • Del Rosso JQ, et al. J Drugs Dermatol 5(2):160-4 (2006 Feb).
  • Gollnick H, et al. J Am Acad Dermatol 49(1 Suppl):S1-37 (2003 Jul).
  • Webster GF. J Am Acad Dermatol 39(2 Pt 3):S38-44 (1998 Aug).
  • Nyirady J, et al. Cutis 70(5):295-8 (2002 Nov).
  • Jain S. J Dermatolog Treat 15(4):200-7 (2004 Jul).
  • Taylor SC. Cutis 80(1 Suppl):15-20 (2007 Jul).