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Q/ Which oral antibiotics are best for acne?

EVIDENCE-BASED ANSWER

A/ DOXYCYCLINE IS EFFECTIVE (strength of recommendation [SOR]: B, randomized controlled trial) and the antibiotic of choice (SOR: C, expert opinion) for moderate to severe inflammatory acne requiring oral treatment. Limiting side effects include photosensitivity and gastrointestinal (GI) disturbance.

Other members of the tetracycline family are considered second-line agents because of their side-effect profile and are contraindicated in pregnancy and for children younger than 12 years (SOR: A, meta-analysis, and C, expert opinion). For these patients, erythromycin is effective and better studied than azithromycin (SOR: C, expert opinion). Otherwise, emerging resistance and GI disturbances make erythromycin a third-line treatment.

The use of oral antibiotics should be limited to moderate to severe inflammatory acne unresponsive to topical therapies, including retinoids and antibiotics (SOR: C, expert opinion). Oral antibiotics should be used for at least 6 to 8 weeks and discontinued after 12 to 18 weeks of therapy (SOR: C, expert opinion).

Evidence summary

Acne vulgaris is an extremely common disorder affecting up to 95% of adolescents. (1) Doxycycline improves inflammatory lesions and has a tolerable side-effect profile.

Doxycycline: Fewer lesions, few side effects

A 2003 randomized, double-blind, controlled trial of 51 patients demonstrated that a sub-antimicrobial dose of doxycycline (20 mg orally twice a day) reduced comedonal lesions by 53.2% (from 31 to 16; P=.04) and inflammatory lesions by 50.1% (from 55 to 25; P<.01), whereas placebo decreased comedonal lesions by 10.6% (from 51 to 46; P=-.4) and inflammatory lesions by 30.2% (from 27 to 19; P<.01). (2)

The most commonly reported adverse effects of doxycycline are GI disturbance and sensitivity to ultraviolet radiation (sunlight). A recent systematic review found an adverse event rate of 13 per 1 million prescriptions written. (3)

Minocycline: Probably effective, but not the first choice

A 2003 Cochrane review examined 27 randomized trials that compared oral minocycline with placebo or other active treatments, including topical and systemic antibiotics, in a total of 3031 patients with acne vulgaris on the face or upper trunk. (4) The review determined that minocycline is probably an effective treatment for moderate acne vulgaris. However, no reliable evidence from randomized controlled trials (RCTs) justifies its use as a first-line agent, especially given its higher cost relative to other treatments.

Drug resistance weakens macrolides' "punch"

Macrolide antibiotics, primarily erythromycin, were at one time considered first-line treatment for acne, but have fallen out of favor because of emerging drug resistance. Nevertheless, erythromycin's price and safety in pregnant women and young children has maintained its standing in acne therapy. A 1986 RCT that compared erythromycin with tetracycline found comparable efficacy: a 65% reduction in papules, from 21 to 12 lesions, for erythromycin and a 62% reduction, from 17 to 10 lesions, for tetracycline (P<.0001). (5) The main side effect of macrolide antibiotics is GI disturbance.

A 2006 RCT randomized 290 patients to the macrolide azithromycin (500 mg daily for 3 consecutive days a week in the first month, then 250 mg every other day for 2 months) or tetracycline (1 g daily for 1 month, then 500 mg daily for 2 months). The drugs produced comparable results: an 84.7% improvement with azithromycin and a 79.7% improvement with tetracycline (P<.05). (6) Compared with other macrolides and tetracycline, azithromycin has a more tolerable side-effect profile with fewer GI disturbances.

Lack of sufficient data on trimethoprim [+ or -] sulfamethoxazole, fluoroquinolones, and cephalosporins precludes their inclusion in routine acne treatment.

Recommendations

The American Academy of Pediatrics (AAP) recommends topical retinoids as the foundation of treatment for most acne patients, and a topical microbial agent for additional therapy. Oral antibiotics should be reserved for moderate to severe inflammatory acne; tetracyclines are the standard first-line choice in most cases. The AAP warns against giving tetracyclines to children younger than 10 years because of the risk of permanent discoloration of teeth and abnormal skeletal development. (7, 8)

The American Academy of Dermatology also recommends topical retinoids as first-line therapy for acne followed by oral doxycycline or minocycline if needed. Erythromycin is recommended for patients who can't use tetracyclines, but with a warning about possible bacterial resistance. (9)

TABLE 1 shows the cost of various acne medications. TABLE 2 outlines their safety and risk profiles.

References

(1.) Amin K, Riddle CC, Aires DL et al. Common and alternate oral antibiotic therapies for acne vulgaris: a review. J Drugs Dermatol. 2007;6:873-880.

(2.) Skidmore R, Kovach R, Walker C, et al. Effects of subantimicrobial-dose doxycycline in the treatment of moderate acne. Arch Dermatol. 2003;139:459-464.

(3.) Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clin Ther. 2005;27:1329-1342.

(4.) Garner SE, Eady EA, Popescu C, et al. Minocycline for acne vulgaris: efficacy and safety. Cochrane Database Syst Rev. 2003;(1):CD002086.

(5.) Gang-non WR, Meyer C, Lantis S, et al. Comparative efficacy of oral erythromycin versus oral tetracycline in the treatment of acne vulgaris. A double-blind study, l Am Acad Dermatol. 1986;14:183-186.

(6.) Rafiei R, Yaghoobi R. Azithromycin versus tetracycline in the treatment of acne vulgaris. J Dermatol Treat. 2006; 17:217-221.

(7.) Hurwitz S. Acne vulgaris: pathogenesis and management. Pediatr Rev. 1994;15:47-52.

(8.) Zaenglein AL, Thiboutot DM. Expert committee recommendations for acne management. Pediatrics. 2006; 118:1188-1199.

(9.) Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol. 2007; 56:651-663.

Meghan Gannon, MD Spring Hill Family Health Group, Spring Hill, Tenn

Michael Underhill, DO Paseo Family Physicians, Glendale, Adz

Kay E. Wellik, MLS, AHIP Mayo Clinic Arizona, Scottsdale

ASSISTANT EDITOR

Carmen G. Strickland, MD, MPH Wake Forest School of Medicine, Family Medicine Residency Program, Winston-Salem, NC
TABLE 1
Estimated cost of oral acne medications

                      Dose, formulation,         Cost of 30-
Medication              and frequency            day supply *

Doxycycline          100 mg capsule daily           $12.99
hyclate

Doxycycline          100 mg tablet daily            $20.99
hyclate

Extended-             45 mg tablet daily           $450.97
release
minocycline

Minocycline       100 mg capsule twice a day        $45.98

Minocycline       100 mg tablet twice a day        $227.98

Erythromycin    250 mg enteric-coated capsule      $154.62
base                    4 times a day

Erythromycin     250 mg tablet 4 times a day       $114.62
base

Azithromycin         500 mg tablet daily,          $175.20
                          3 days/wk

* http://www.drugstore.com. Accessed April 10, 2011.

TABLE 2
Safety and adverse-effect profiles of acne medications (8)

Medication     Adverse effects               Pregnancy
                                             category

Doxycycline    Photosensitivity, GI              D
hyclate        disturbance, elevated BUN

Minocycline    Tooth discoloration,              D
               dizziness, hypersensitivity
               syndrome

Erythromycin   GI disturbance, nausea            B
base

Azithromycin   Abdominal pain,                   B
               GI disturbance

Medication      Lactation     Appropriate age
                  safety           range

Doxycycline       Avoid             >12y
hyclate

Minocycline       Avoid;            >12y
               milk effects
                 possible

Erythromycin       Safe         FDA-approved
base                            for children

Azithromycin   Minimal risk   Extended-release
                                formula not
                                FDA-approved
                                for children

BUN, blood urea nitrogen; GI, gastrointestinal.
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Article Details
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Title Annotation:CLINICAL INQUIRIES: Evidence-based answers from the Family Physicians Inquiries Network
Author:Gannon, Meghan; Underhill, Michael; Wellik, Kay E.
Publication:Journal of Family Practice
Geographic Code:1USA
Date:May 1, 2011
Words:1128
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