Antimicrobial Therapy in Acne (2)

MACROLIDES
Topical and oral erythromycin and topical clindamycin have been well-established acne treatments for decades, but have become much less effective in the past 15 years or so due to the acquisition of resistance by P. acnes. Resistant bacteria are now induced quickly by macrolide therapy because most patients have a portion of their normal skin flora that is genetically resistant, and that subgroup expands under the selective pressure of therapy (8–11). Resistant bacteria make for acne that resists therapy and erythromycin resistant strains are typically resistant to clindamycin and vice versa.Resistance can be combated by the addition of BP to topical macrolide regimens. It has been clearly shown that such combination products are not only more effective than monotherapy with macrolides, but also do not permit the survival of resistant populations of P. acnes (6).
Other macrolides for example, azithromycin have been reported in small studies to be of value in acne (12), but no data is available on the effect of resistance on the utility of these drugs.
TETRACYCLINES
The tetracycline family of antibiotics are extremely useful in acne because they have multiple modes of action, functioning as antibiotics that reduce bacterial populations, and as anti-inflammatory drugs that attack acne from a second front.Tetracyclines, especially doxycycline and minocycline are highly antiinflammatory in many cell systems (Table 1). Neutrophil and monocyte chemotaxis is inhibited through calcium chelation, blunting the migration of cells to the follicle(13). Granuloma formation in vitro (14) and in vivo (15) is inhibited; with minocycline and doxycycline roughly 10-fold more active than tetracycline. In this model, macrolides and cephalosporines were inactive. Protein kinase C is inhibited
(15), perhaps interfering with signal transduction. Generation of reactive oxygen species and the oxidative burst in neutrophils is decreased (16). Nitric oxide production ismodulated (17).Matrix metalloprotease and collagenase activity is inhibited (18–20). In vivo, tetracyclines have been demonstrated to be highly active in treating purely inflammatory diseases including rheumatoid arthritis, bullous pemphigoid, and sarcoidosis (21). Nonantibiotic derivatives of doxycycline have been recently developed that are highly anti-inflammatory and even antineoplastic through inhibition of angiogenesis and may be of use in acne and other inflammatory diseases (22–24).
Concentrations of tetracyclines that are below the antibiotic threshold still have anti-inflammatory activity. Low doses of doxycycline and minocycine that do not affect bacterial growth decrease the production of neutrophil chemoattractants by P. acnes (25,26). Subminimal inhibitory doses also retain the ability to inhibit inflammation in vivo and improve diseases such as acne, rosacea, and periodontitis (27–29).