Where acne and antimicrobial stewardship meet
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Acne vulgaris (acne) is a common dermatologic condition affecting most adolescents and young adults. It is a complex condition that involves multiple factors.
Topical and systemic antibiotics have been a mainstay treatment for decades, although because of an increase in antibiotic resistance, this treatment approach is being revisited. Antibiotic use in acne has not been a focus for many antimicrobial stewardship programs; however, there are several strategies to consider in order to be good antibiotic stewards when treating a patient with acne.
What is acne and why antibiotics?
Acne occurs due to a multitude of factors, including comedo formation, excess oil production, bacterial overgrowth and inflammatory processes. Cutibacterium acnes is a common bacterium within human skin flora and the predominant bacterium associated with acne. In addition to reducing bacteria, it is thought that antibiotics have an anti-inflammatory effect. However, outpatient use of antibiotics does have the potential to contribute to antimicrobial resistance.
What medications are used to treat acne?
The American Academy of Dermatology (AAD) regularly publishes guidelines for acne, most recently in 2016. The AAD recommends a wide range of first-line treatments for acne, based on severity, including topical medications (benzoyl peroxide, retinoids, antibiotics), as well as oral medications (antibiotics or retinoids). In addition to these, alternative treatments included in the AAD algorithm are topical dapsone, spironolactone or hormonal contraception. Topical antibiotics include clindamycin or erythromycin. Oral antibiotics include tetracyclines (tetracycline, doxycycline and minocycline), macrolides (azithromycin and erythromycin) and trimethoprim, which is generally administered with sulfamethoxazole (TMP-SMX).
Antibiotic trends
A repeated cross-sectional analysis of dermatologist prescribing patterns between 2008 and 2016 was published in 2019. Researchers used commercial claims data to identify trends and found a decline in antibiotics from 3.36 to 2.13 courses per 100 visits over the course of the study period. For acne, 96.1% of claims were for extended courses of therapy (defined as > 28 days), with a mean duration of 30 days. This study found doxycycline monohydrate use increased from 5.4% to 9.5%, whereas doxycycline hyclate use decreased from 29.4% to 26%. Minocycline use increased from 22.5% to 25.9% and use of the brand name extended-release minocycline decreased from 21.3% to 17.1%. TMP-SMX and azithromycin use have remained the same at around 8.5% and 1.1%, respectively. The authors hypothesized that the changes in doxycycline and minocycline prescribing are likely due to the high cost of the extended-release brand name minocycline and the rising cost of doxycycline hyclate that started in 2012.
Overall, these trends show tetracycline antibiotics make up approximately 80% of all oral acne antibiotic prescriptions. TMP-SMX makes up around 8% and macrolides less than 3%. This study should be interpreted carefully because claims data do not necessarily provide the full picture of prescribing patterns.
A qualitative interview study of 20 general practitioners in southwest England performed in 2020 identified several themes in their use of antibiotics for acne. Regarding oral antibiotics, these themes included the perception that topical antibiotics have lower efficacy than oral, an unfamiliarity with prescribing oral antibiotics for acne, and low concerns related to prolonged treatment courses. For topical antibiotics, the themes centered around an uncertainty in prescribing (overwhelming number of options, etc.), patient acceptability and side effects.
A retrospective claims data review of more than 30,000 courses of oral antibiotics prescribed for acne between 2008 and 2010 found a mean duration of 129 days. This study looked at patients aged 9 to 21 years and found most durations were shorter than 9 months (93%), but 57.8% of the courses did not include concomitant retinoid therapy. Benzoyl peroxide use was not evaluated because it is sold over the counter, and claims data would not be an effective way to assess trends.
Antimicrobial stewardship
Using broad-spectrum antibiotics in dermatology is common practice but calls into question opportunities for antibiotic stewardship. Aside from their intrinsic side effects, routine use of broad-spectrum antibiotics can change a patient’s microbiome and contribute to antibiotic resistance. As Barbieri and colleagues identified, the use of antibiotics by dermatologists has overall been trending downward. Outside of dermatology, bringing awareness to this topic may be beneficial in primary care settings. Addressing this topic in primary care settings may have a higher yield in terms of optimizing antibiotic use for acne. Below are some strategies to consider.
Consider alternatives first: A review from Dreno and colleagues with the Global Alliance to Improve Outcomes in Acne strongly recommended against oral and topical antibiotics because there are many other efficacious options. Consider trying several nonantibiotic-containing acne regimens first. A review by Barbieri and colleagues in 2019 summarized the evidence and proper use of other systemic alternatives. Efficacious alternatives include spironolactone 25 to 100 mg daily, oral contraceptives and isotretinoin. These therapies may not be appropriate for all patients but would be options to consider. Nonpharmacological options include photodynamic therapy, light-based laser treatments and dietary modifications.
Use in combination: As recommended by AAD guidelines, antibiotics should be used in combination with nonantibiotic options to prevent and slow the development of resistance. If topical antibiotics are used, they should be administered alongside benzoyl peroxide to limit the development of resistance.
Limit duration: If antibiotics are used, frequently assess for efficacy and adherence. Cease use after 3 months if able or after 6 months if the patient continues to experience significant clinical improvement. The AAD recommends limiting treatment duration and using antibiotics in combination with topical therapies. Limiting duration is important, the organization said, because of “reported associations of inflammatory bowel disease, pharyngitis, [Clostridioides] difficile infection, and the induction of Candida vulvovaginitis.” If antibiotics are to be used, they should be reserved for moderate to severe acne. Efficacy can be noted at 4 to 8 weeks of treatment, and total duration should be limited to 12 to 16 weeks. Treating up to 24 weeks is acceptable if there is notable clinical improvement.
Conclusion
Antibiotics have been a mainstay of acne treatment for decades. However, their use does have drawbacks: perpetuating antimicrobial resistance, altering skin flora and generating antibiotic-specific side effects. There are other efficacious and safe options recommended by the AAD that could be tried before antibiotics. If antibiotics are to be used, being a good antimicrobial steward can help slow resistance. Physicians should use antibiotics in combination with a nonantibiotic medication and limit the duration as able.
- References:
- Barbieri JS, et al. J Am Acad Dermatol. 2019;doi:10.1016/j.jaad.2018.09.055.
- Barbieri JS, et al. JAMA Dermatol. 2019;doi:10.1001/jamadermatol.2018.4944.
- Bell, EA. Antibiotics for acne — How long is too long? https://www.healio.com/news/pediatrics/20180309/antibiotics-for-acne-how-long-is-too-long. March 14, 2018.
- Dreno B, et al. Eur J Dermatol. 2014;doi:10.1684/ejd.2014.2309.
- Graber, E. Acne vulgaris: Management of moderate to severe acne. UpToDate. https://www.uptodate.com/contents/acne-vulgaris-overview-of-management. Updated February 17, 2021. Accessed March 5, 2021.
- Lee HL, et al. J Am Acad Dermatol. 2014;doi:10.1016/j.jaad.2014.02.031.
- McLaughlin J, et al. Microorganisms. 2019;doi:10.3390/microorganisms7050128.
- Platt D, et al. Br J Gen Pract. 2020;doi:10.3399/bjgp20X713873.
- Zaenglein AL, et al. J Am Acad Dermatol. 2016;doi:10.1016/j.jaad.2015.12.037. [published correction appears in J Am Acad Dermatol. 2020 Jun;82(6):1576].
- For more information:
- Hannah Van Ochten, PharmD, MPH, is a PGY1 pharmacy resident at Denver Health Medical Center.
- Kati Shihadeh, PharmD, BCIDP, is a clinical pharmacy specialist in infectious diseases at Denver Health Medical Center. Shihadeh can be reached at katherine.shihadeh@dhha.org.
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