What antibiotics are used to treat moderate to severe acne?

Antibiotics for Moderate to Severe Acne

First-Line Systemic Antibiotic Therapy

Doxycycline (100mg daily) is the first-line oral antibiotic for moderate to severe inflammatory acne and must always be combined with topical benzoyl peroxide and/or a retinoid—never use oral antibiotics as monotherapy. 1, 2, 3

When to Use Systemic Antibiotics

• Systemic antibiotics are indicated for moderate to severe inflammatory acne that is widespread or resistant to topical treatments alone 1, 2
• They work through dual mechanisms: inhibiting bacterial protein synthesis at the 30S ribosomal subunit and providing anti-inflammatory effects by inhibiting chemotaxis and metalloproteinase activity 1, 3
• Patients must be 8 years or older (tetracyclines cause tooth discoloration in younger children) 1, 2

Doxycycline: The Preferred First Choice

• Doxycycline has demonstrated superiority over azithromycin in randomized controlled trials and should be tried before other options 3
• Standard dosing is 100mg daily for adults; for children 8+ years but under 100 pounds, use 2mg/lb divided into 2 doses on day 1, then 1mg/lb daily 3, 4
• Even subantimicrobial dosing (20-40mg daily) shows efficacy in moderate inflammatory acne 1, 3, 5
• FDA-approved for severe acne as useful adjunctive therapy 4

Key side effects to counsel patients about:

• Photosensitivity (more common than with minocycline)—advise sun protection 3
• Gastrointestinal disturbances, particularly at higher doses 3, 6
• Contraindicated in pregnancy (Category D) and children under 8 years 3

Second-Line Tetracycline Option

Minocycline: When Doxycycline Fails or Is Not Tolerated

• Minocycline (50-100mg daily) is the second-line tetracycline choice if doxycycline causes intolerable GI upset or photosensitivity 2, 7
• Minocycline has superior lipophilicity, achieving high concentrations in the pilosebaceous unit 6
• Less frequent GI disturbances and photosensitivity compared to doxycycline 7, 6
• FDA-approved for severe acne as useful adjunctive therapy 8

Important warnings specific to minocycline:

• Higher risk of serious adverse effects including hyperpigmentation, autoimmune disorders, and serum sickness-like reactions (though rare) 7, 6
• Vestibular side effects (dizziness, vertigo) are dose-related 6, 9
• Extended-release formulation (1mg/kg daily) reduces vestibular adverse events to placebo levels 7, 9

Alternative Antibiotics for Special Circumstances

When Tetracyclines Cannot Be Used

For pregnant women or children under 8 years, use erythromycin or azithromycin, though these are inferior options: 1, 7

• Erythromycin use should be restricted due to high rates of bacterial resistance 1
• Azithromycin is inferior to doxycycline in head-to-head trials and should only be used when tetracyclines are contraindicated 1, 7
• The American Academy of Dermatology states there is insufficient evidence to develop formal recommendations for azithromycin or trimethoprim-sulfamethoxazole 7

Trimethoprim-Sulfamethoxazole: Last Resort Only

• Reserve for patients unable to tolerate tetracyclines or in treatment-resistant cases 1
• Associated with severe adverse reactions including Stevens-Johnson syndrome/toxic epidermal necrolysis and acute respiratory failure 7
• Broad use should be discouraged to prevent antibiotic-resistant bacteria 7

Critical Treatment Principles to Prevent Resistance

Mandatory Combination Therapy

Monotherapy with systemic antibiotics is explicitly not recommended—always combine with topical benzoyl peroxide and/or a retinoid: 1, 2, 3, 7

• Concomitant topical therapy prevents bacterial resistance development 1, 2
• Continue topical therapy for maintenance after completing systemic antibiotics 1
• The combination of oral antibiotics with topical therapy is superior to oral antibiotics alone 10

Duration and Monitoring Algorithm

• Limit systemic antibiotic duration to 3-4 months maximum 1, 2, 7
• Re-evaluate at 3-4 months to assess response and minimize bacterial resistance 1, 2
• Clinical improvement typically occurs within 1-2 weeks of treatment initiation 2
• If inadequate response after 3-4 months with proper combination therapy, consider isotretinoin for severe cases 3

Common Pitfalls to Avoid

• Never prescribe oral antibiotics without concurrent topical benzoyl peroxide or retinoid—this is the most common error leading to resistance 1, 2, 7
• Do not continue antibiotics beyond 3-4 months without reassessment 1, 2, 7
• Do not use tetracycline or erythromycin as first-line agents—resistance rates are too high 1, 11
• Avoid skipping doxycycline and moving directly to newer agents like sarecycline without justification 2
• Do not forget to counsel about photosensitivity with doxycycline 2, 3

Treatment Algorithm Summary

1. Start with doxycycline 100mg daily + topical benzoyl peroxide + topical retinoid 2, 3
2. If doxycycline not tolerated (GI upset/photosensitivity): switch to minocycline 50-100mg daily 2, 7
3. If tetracyclines contraindicated (pregnancy, age <8 years, allergy): use erythromycin or azithromycin 1, 7
4. Re-evaluate at 3-4 months; if inadequate response, consider isotretinoin 1, 2, 3
5. Continue topical therapy indefinitely for maintenance after stopping oral antibiotics 1