Antibiotic use — primarily use of bacteriostatic antibiotics such as erythromycin and clindamycin — is resulting in Propionibacterium acnes resistance, according to an overview of clinical evidence published in JAMA Dermatology.1 Indeed, data point to an epidemiologic crisis in which more than 50% of P. acnes strains are resistant to topical antibiotics, namely erythromycin and clindamycin and, to a lesser extent, tetracyclines.2,3 Topical antibiotics also are being associated with Staphylococcus aureus resistance, and the use of bacteriostatic antibiotics may be associated with an increased risk for upper respiratory infections and pharyngitis.

The investigators, who are affiliated with the Keck School of Medicine at the University of Southern California, Los Angeles, and Drexel University College of Medicine in Philadelphia, Pennsylvania, point out that dermatologists disproportionately prescribe antibiotics for the treatment of acne, typically using bacteriostatic agents, which are suspected of encouraging the emergence of resistant P. acnes strains. 2

They reviewed 5 US and European trials that included 120,088 outpatients whose mean age was 22 years (range, 12 to 59 years). The studies sought to determine the prevalence of antibiotic-resistant P. acnes in patients treated for acne and their close contacts; nasal/pharyngeal colonization of S. aureus and antibiotic susceptibility patterns; and prevalence of upper respiratory infections, pharyngitis, and urinary tract infections.


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In addition to the high rate of resistant P. acnes strains, data reviewed showed that use of antibiotics for the treatment of acne had “off-target” effects: topical antibiotics were linked to S. aureus resistance; prolonged use of oral or topical antibiotics (≥6 weeks) was associated with a significantly (P <.001) increased risk for upper respiratory infections within the year following treatment; and use of oral antibiotics was associated with a more than 4-fold risk for pharyngitis within the year following treatment.  

AAD Guidelines Reviewed

In light of these findings, the authors reviewed current American Academy of Dermatology (AAD) guidelines regarding antibiotic stewardship and the recommended treatment of acne.4 The guidelines recommend use of benzoyl peroxide in conjunction with topical and oral antibiotics, as benzoyl peroxide is comedolytic, has activity against P. acnes, and may help prevent emergence of antibiotic resistance.

Recommended first-line treatment for mild-to-moderate acne per the AAD is benzoyl peroxide, a topical retinoid, or combination therapy in which benzoyl peroxide is used with a retinoid and/or an antibiotic. First-line treatment for moderate-to-severe acne is an oral antibiotic combined with benzoyl peroxide and a topical retinoid. Topical antibiotics also can be included but only if benzoyl peroxide is also part of the treatment regimen. Antibiotic monotherapy is strongly discouraged, and duration of therapy preferably should not exceed 4 months, after which benzoyl peroxide and topical retinoids are the recommended maintenance therapy.

The investigators advocated for studies on the exact impact of benzoyl peroxide and combination therapy on treatment efficacy and whether and to what degree benzoyl peroxide may inhibit antimicrobial resistance to antibiotics. “There is a pressing need for high-quality studies examining the impact of some of our most commonly used acne treatments on antibiotic resistance in P. acne,” lead investigator Brandon Adler, MD, of the Keck School of Medicine, told Dermatology Advisor. “While limited in scope, the published literature suggests that real-life consequences occur due to overuse of antibiotics for acne — not only treatment failure, but resistance formation in unrelated bacteria and increased incidence of common infections. Professional society guidelines advocate for measures to stem resistance development. Just how effective these are remains to be determined. In this era of superbugs and meager antibiotic development, it is prudent to shield patients from unrestrained antibiotic exposure. By highlighting these gaps in research and practice, we hope to encourage further inquiry into crucial yet poorly understood aspects of one of the most commonly encountered dermatologic conditions.”

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Summary and Clinical Applicability

Use of macrolide antibiotics is associated with emergence of resistant P. acnes and S. aureus strains and increased risk for upper respiratory infections. Dermatologists are advised by the AAD to avoid antibiotic monotherapy, use combination treatment that incorporates benzoyl peroxide, and to limit the duration of oral antibiotic use to ≤4 months.

Limitations

The authors noted that data on antibiotic resistance in the treatment of acne are limited in scope and quality.

References

  1. Adler BL, Kornmehl H, Armstrong AW. Antibiotic resistance in acne treatment. JAMA Dermatol. 2017;153:810-811.
  2. Walsh TR, Efthimiou J, Dréno B. Systematic review of antibiotic resistance in acne: an increasing topical and or oral threat. Lancet Infect Dis. 2016;16:e23-e33.
  3. Ross JI, Snelling AM, Carnegie E, et al. Antibiotic-resistant acne: lessons from Europe. Br J Dermatol. 2003;148(3):467-478.
  4. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-973.e33