Systemic antibiotics: Recommendations

What is the effectiveness and what are the potential side effects of systemic antibacterial agents in the treatment of adult acne and acne vulgaris in adolescents to adults including:

  • Tetracylclines: doxycycline and minocycline
  • Macrolides: erythromycin and azithromycin
  • Clindamycin
  • Trimethoprim (with or without sulfamethoxazole)
  • Ampicillin/amoxicillin

  • Systemic antibiotics are recommended in the management of moderate and severe acne, and forms of inflammatory acne that are resistant to topical treatments.
  • Doxycycline and minocycline are more effective than tetracycline, but neither is superior to each other.
  • Although oral erythromycin and azithromycin can be effective in treating acne, its use should be limited to those who cannot use the tetracyclines (i.e., pregnant women or children under 8 years of age). Erythromycin use should be restricted due to its increased risk of bacterial resistance.
  • Use of systemic antibiotics, other than the tetracyclines and macrolides, is discouraged as there is limited data for their use in acne. Trimethoprim-sulfamethoxazole and trimethoprim use should be restricted to patients unable to tolerate tetracyclines or in treatment resistant patients. 
  • Systemic antibiotic use should be limited to the shortest possible duration, typically 3 months, to minimize the development of bacterial resistance. Monotherapy with systemic antibiotics is not recommended.
  • Concomitant topical therapy with benzoyl peroxide and/or a retinoid should be used with systemic antibiotics, as well as for maintenance after completion of systemic antibiotic therapy.
  Strength of Recommendation  Level of Evidence
(tetracycline, doxycycline, minocycline) 
(azithromycin, erythromycin) 
TMP w/ or w/o SMX  II 
Limiting treatment duration and concomitant/maintenance topical therapy  I,II 

Review prescribing information for recommended acne treatments.

Systemic antibiotics have been a mainstay of acne treatment for years. They are indicated for use in moderate to severe inflammatory acne and should be used in combination with a topical retinoid and BP.95,192,193 Evidence supports the efficacy of tetracycline, doxycycline, minocycline, trimethoprim/sulfamethoxazole (TMP/SMX), trimethoprim, erythromycin, azithromycin, amoxicillin, and cephalexin. 

The tetracycline class of antibiotics should be considered first-line therapy in moderate to severe acne, except when contraindicated because of other circumstances (ie, pregnancy, ≤8 years of age, or allergy). The antibiotics of the tetracycline class work by inhibiting protein synthesis by binding the 30S subunit of the bacterial ribosome. This class also has notable antiinflammatory effects, including inhibiting chemotaxis and metalloproteinase activity. Previous guidelines recommended minocycline as superior to doxycycline in reducing P acnes.1 However, a recent Cochrane review of clinical trials found minocycline effective but not superior to other antibiotics in the treatment of acne.88 There are few studies addressing dosing of the tetracycline class. Minocycline in an extended release form appears safest (at 1 mg/kg), but no dose response was found for efficacy.194 Doxycycline appears effective in the 1.7 to 2.4 mg/kg dose range.89 Subantimicrobial dosing of doxycycline (i.e., 20 mg twice daily to 40 mg daily) has also shown efficacy in patients with moderate inflammatory acne.195,196

Erythromycin and azithromycin have also been used in the treatment of acne. The mechanism of action for the macrolide class of antibiotics is to bind the 50S subunit of the bacterial ribosome. Again, there are some antiinflammatory properties for these medications, but the mechanisms are not well understood. Azithromycin has been primarily studied in the treatment of acne in open label studies with different pulse dosing regimens ranging from 3 times a week to 4 days a month, with azithromycin being an effective treatment in the time span evaluated—usually 2 to 3 months.92,197-204 A recent randomized controlled trial comparing 3 days per month of azithromycin to daily doxycycline did show superiority of doxycycline.205 Macrolides as the penicillin class represent an alternative when traditional antibiotics cannot be used.

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