http://www.nyccosmeticdermatology.com/oral-antibiotics-therapies.htm
Tetracyclines
Since tetracycline (tetracycline hydrochloride and oxytetracycline) first became available in 1953, followed by doxycycline in 1967 and minocycline in 1972, the tetracyclines have become the most commonly prescribed first-line systemic antibiotic for the treatment of acne. (Lymecycline, a second-generation tetracycline introduced in 1963, is used outside of the US for acne and will not be discussed further here.) Tetracyclines are antimicrobials that exert a bacteriostatic effect by interfering with protein synthesis on the 30S ribosomal subunit. Additionally, these agents exert anti-inflammatory properties by inhibiting chemotaxis, decreasing the formation of reactive oxygen species, inhibiting proteolytic matrix metalloproteinases, and downregulating proinf1ammatory cytokines. They also alter sebum excretion by inhibiting phospholipase A2 metabolism of arachidonic acid and P. acnes-derived lipase, resulting in a
decreased accumulation of follicular free fatty acids that serve as potent chemokines for neutrophil recruitment. Tetracycline, administered in doses of 5OO mg twice daily followed by 500 mg daily, can be an inexpensive, effective, and generally safe treatment. Because the absorption of tetracycline is affected by food, dairy products, antacids, vitamins, and iron, taking it on an empty stomach is recommended. Adverse effects most commonly include gastrointestinal distress manifested as diarrhea, vomiting, dyspepsia, and, rarely, esophagitis and esophageal ulceration. Vaginal candidiasis, acneiform and fixed drug eruptions, benign intracranial hypertension, photosensitivity, and, rarely, severe cutaneous reactions such as Stevens-Johnson syndrome can also occur. Cross-reactivity is more frequent with doxycycline than with minocycline, as the former is more chemically similar. Tetracyclines should be avoided by pregnant women as they cause discoloration and enamel hypoplasia of deciduous teeth, and in children younger than 8 due to staining of the developing permanent teeth.
Doxycycline is a broad-spectrum antibiotic synthetically derived from tetracycline and is available as several different forms: doxycycline monohydrate, doxycycline hydrochlotide hemierhanolate hemihydrate, doxycycline hyclate, and doxycycline calcium (Table 2). It is more lipophilic than tetracycline and has demonstrated excellent penetration into the pilosebaceous unit. lts side effect profile parallels that of tetracycline, with the exception that doxycycline is more likely to cause phororoxic reactions.
For patients with gastrointestinal complaints, capsules of doxycycline in the form of enteric-coated pellets (Doryx®) may be a viable alternative. Doryx was shown to result in fewer gastrointestinal side effects when compared to capsules containing the powdered form.
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With the worldwide emergence of P. acnes strains resistant to tetracyclines, recent studies have demonstrated therapeutic efficacy with doxycycline administered at doses below necessary for its antimicrobial properties. Subantimicrobial-dose doxycycline (SDD) hyclate 20 mg twice daily (Periosta®) was approved by the US FDA in 1998 for chronic adult periodontitis, and in 2006 for the treatment of rosacea in the form of 40 mg once daily (Oracea®). In 2003, Skidmore et al published the first acne trial examining the antiinflammatory properties of a tetracycline derivative independent of its antimicrobial effect. In this randomized, double-blind, controlled trial, participants with moderate facial acne were treated with either doxycycline hyclate 20 mg twice daily (n=2 I) or placebo (n=19) for 6 months. Skin samples were collected pre- and post-treatment to evaluate whether SDD therapy altered normal skin flora, had an antimicrobial effect. or resulted in antibiotic resistance.
At 6 months, the doxycycline group had significantly greater improvement according to the clinician’s global assessment. Comedonal and inflammatory lesions were reduced by 53.2% and 50.1%, respectively, compared to 10.6% and 30.2% lesion reductions in the placebo group. SDD had no effect on the composition of skin microflora, and did not result in organisms resistant to doxycycline or cross-resistant to other antimicrobials. Both SDD and placebo were equally well-tolerated.
This was followed by a smaller study in which 12 patients were first given doxycycline hyclate 100 mg daily for 8 weeks. This produced a 50% reduction of lesions in all that remained enrolled (n=11). Six of these patients were subsequently given doxycycline hyclate 20 mg BID while the rest received placebo. The former group maintained improvement, while the latter did not. Although there have becn few studies on SDD thus far, it appears to be an effective treatment for clinically improving acne vulgaris while having an undetectable antimicrobial effect, potentially minimizing the emergence of resistant organisms and colonization of the skin with opportunistic pathogens. Unfortunately, there are no studies comparing the clinical efficacy of subantimicrobial doses to conventional doses of doxycycline for acne treatment.
