Balancing Innovation and Tradition: A Modern Look at Oral Antibiotics in Acne Treatment Overview: Acne as a Chronic Inflammatory Disease

Supported by an independent medical grant by Almirall.

Overview: Acne as a Chronic Inflammatory Disease

Acne is a common, chronic skin condition affecting approximately 9% of the worldwide population, including more than 85% of teenagers, and is the reason for approximately two-thirds of dermatology consultations.¹ Acne lesions can cause permanent scarring and skin pigmentation that requires ongoing treatment.¹ People with acne often report physical and emotional discomfort, as well as anxiety and self-consciousness that may lead to depressive symptoms.¹ The presence of acne negatively affects quality of life, particularly among those who are older than 25 years of age or have higher-grade acne, severe scars, and postacne hyperpigmentation.²

The pathogenesis of acne involves 4 pillars: excess sebum production, hyperkeratinization of the pilosebaceous follicles, excess proliferation of the Cutibacterium acnes bacteria, and inflammation.¹ Several other variables can also induce or exacerbate acne, including genetics, environmental factors (eg, temperature, humidity, pollution, sun exposure, mineral oils, halogenated hydrocarbons), nutrition, hormone fluctuations, stress, smoking, medications (eg, androgens, corticosteroids), bacteria, and cosmetics.¹ Environmental stressors may also induce epigenetic alterations, which may play a role in the development and progression of acne and other inflammatory skin diseases.¹

Evolving Clinical Practice and Use of Oral Antibiotics

Treatment of acne typically involves a multimodal approach that includes topical therapies (eg, retinoids, benzoyl peroxide, antibiotics, clascoterone, salicylic acid, azelaic acid), systemic and oral options (eg, antibiotics, oral contraceptives, spironolactone, intralesional corticosteroids), and isotretinoin for severe cases.³ Topical therapies alone may be adequate for mild to moderate cases, while more severe cases often require the addition of systemic/oral options to topical therapy or isotretinoin.³ Isotretinoin can also be used as a first-line therapy for patients with significant psychosocial burden or scarring.³

Oral antibiotics, particularly those in the tetracycline class, have been a mainstay for the treatment of severe acne, particularly for lesions located on the face and trunk.³ However, the high prescribing rates among dermatologists and growing concerns about antibiotic resistance and potential adverse effects have shifted the focus to more strategic use of oral antibiotics, such as those with shorter courses, a narrower spectrum of action, and in combination with topical therapies, according to Naiem Issa, MD, PhD, FAAD.³ According to data from the Centers for Disease Control and Prevention, dermatologists had the highest rate of antibiotic prescriptions of all medical specialties, and a retrospective analysis showed that while antibiotic prescriptions for acne decreased from 2008 to 2016, acne accounted for the largest number of extended-course antibiotic prescriptions in dermatology practices in 2016.^4,5 In their 2024 guidelines, the American Academy of Dermatology (AAD) advised antibiotic stewardship when possible to minimize the risk for development of antibiotic resistance and other complications associated with antibiotic use, such as inflammatory bowel disease, pharyngitis, Clostridium difficile infection, and Candida vulvovaginitis.³ They also advised using oral antibiotics in conjunction with other topical therapies (ie, avoiding monotherapy) and for the shortest possible duration (maximum of 3 to 4 months).³

Issa noted that the use of isotretinoin instead of oral antibiotics as the first treatment option for severe acne has been increasing in recent years, as isotretinoin is thought to be the only agent that addresses all 4 pillars of acne pathogenesis.¹ However, some patients are slow responders and/or may experience temporary worsening of acne, and Issa noted that the rapid response of acne to oral antibiotics can improve patient confidence in the treatment journey, even for patients who plan to use isotretinoin in the future.⁶ Issa said that he usually starts with oral antibiotics to stop the acne-associated inflammation as soon as possible and then follows up with isotretinoin as needed.

Types and Mechanisms of Action of Oral Antibiotics

Tetracycline-class antibiotics doxycycline, minocycline, and sarecycline are approved by the Food and Drug Administration (FDA) to treat moderate to severe acne and exert their antimicrobial effects by binding to the 16S ribosomal RNA of the bacterial ribosome 30S subunit, which interferes with bacterial protein synthesis.³ In addition to suppression of P. acnes growth, the tetracycline class of antibiotics has anti-inflammatory properties, notably decreased neutrophil chemotaxis and blockade of proinflammatory cytokines and matrix metalloproteinases, that are relevant in the treatment of acne.⁷ The anti-inflammatory effect is even present at low doses and may play a particularly important role, given that increased inflammation is present before identifiable lesions are present.⁷ According to Issa, the balance lies in finding the minimal effective dose that promotes antimicrobial and anti-inflammatory effects while reducing the risk for treatment-related adverse events and antibiotic resistance.

Doxycycline and minocycline are more lipophilic than their parent tetracycline, which improves their ability to penetrate and accumulate in the sebaceous gland where the C. acnes bacteria grow.⁷ Gastrointestinal (GI) adverse effects (eg, nausea, vomiting, and diarrhea) are often observed with doxycycline and may be mitigated by taking the drug with food (this decreases absorption by about 20%; however, the clinical significance is negligible in the context of acne treatment).⁷ Minocycline has even higher lipophilicity than doxycycline, which enables adequate absorption when dosing with food and using lower doses.⁷ Additionally, a smaller amount of active drug lingers in the GI tract, which may decrease the likelihood of GI-related adverse events compared with doxycycline.⁷ However, the high permeability of minocycline increases its likelihood of crossing the blood-brain barrier, possibly leading to acute vestibular adverse events (eg, dizziness, vertigo).⁷ Rare but serious adverse events such as irreversible hyperpigmentation, drug hypersensitivity, Stevens-Johnson syndrome, and lupus-like autoimmune reactions have also been reported with minocycline.⁷

Despite their effectiveness in treating acne, the broad spectrum of activity with doxycycline and minocycline can also lead to long-term consequences, such as disruptions in the microbiome, antimicrobial resistance that can decrease the effectiveness of this antibiotic class for treatment of future infectious diseases, and development of multidrug-resistant bacteria.⁸ Issa noted that doxycycline-resistant bacteria may develop in as little as 2 weeks of use, and even a short (7-day) course of antibiotics can alter the gut microbiome for 2 years. Therefore, there has been an increased desire to incorporate narrow-spectrum tetracycline-class antibiotics for acne to reduce the short- and long-term effects of broad-spectrum tetracycline-class antibiotics.⁸ Sarecycline is a newer narrow-spectrum tetracycline antibiotic that was FDA-approved for acne in 2018 and may be less likely to contribute to antimicrobial resistance than doxycycline or minocycline.⁷ Issa noted that sarecycline tends to work particularly well on truncal acne, which can be difficult to treat with topical therapies. Furthermore, the rates of treatment-emergent adverse effects commonly observed with tetracycline-class antibiotics were low in the phase 3 SC1401 (NCT02320149) and SC1402 (NCT02322866) trials, suggesting that sarecycline may be a more tolerable option for patients.⁸ The AAD guidelines note that while clinical trial evidence supports high certainty of benefits over risks, access to sarecycline may be limited by its high cost.³

Patient Selection and Clinical Decision-Making

Oral antibiotics are commonly used for patients with acne that is moderate or severe, inflammatory, nonresponsive to prior topical treatment, and/or encompasses a large body area.¹ The 2024 AAD guidelines give conditional recommendations for their use in combination with benzoyl peroxide and other topical therapies in patients with moderate to severe acne.³

Issa typically discusses the potential use of an oral antibiotic with any patient with moderate to severe acne (provided they do not have general contraindications for oral antibiotics, such as allergies, angioedema, or inability to swallow pills). He educates patients and their parents/caregivers on the role of oral antibiotics as a short-term strategy to quickly reduce inflammatory and noninflammatory lesions and thereby prevent permanent scarring and pigmentary changes, especially for patients with darker skin. He noted that patients and their parents may be hesitant to use oral antibiotics for acne based on misconceptions or concerns about adverse events, and counseling them on the benefits and risks of oral antibiotics is important in gaining their trust.

“I advise people to intervene hard and early for acne because scars are like diamonds,” said Issa. “They last forever, and the majority will not revert back. That’s why [I implement] the oral antibiotics, especially for my moderate [or] severe patients, and try to get them early on in the process before we even have a discussion about isotretinoin.”

However, tetracycline-class antibiotics may not be suitable for all patients with moderate to severe acne. All tetracycline-class antibiotics are thought to be associated with fetal harm (by interfering with bone growth) and should thus be avoided during pregnancy; azithromycin is generally the preferred oral antibiotic for severe acne in pregnant individuals.⁷ Permanent tooth staining with tetracycline-class antibiotics may also be a concern for children with developing teeth; therefore, these agents are not recommended for children younger than 8 years old.⁷ Issa also noted that resistance patterns within a geographic area should be considered when selecting an oral antibiotic, and high resistance to tetracyclines in a region may preclude their use.

Conclusions

According to Issa, oral antibiotics play an important role in the management of moderate to severe acne and may prevent the long-term effects of scarring and hyperpigmentation. Strategic use of oral antibiotics using the lowest effective dose for the shortest effective duration and in conjunction with topical therapies is important to reduce the risk of microbial resistance.³ Providing patient and parent education about the role, risks, and benefits of oral antibiotics for acne treatment is important to reduce patient misconceptions. Newer, narrow-spectrum antibiotics, such as sarecycline, may mitigate risk for antimicrobial resistance; efforts to increase access to these agents when uptake is limited by high cost and/or lack of insurance coverage are important.

References

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2. Hazarika N, Rajaprabha RK. Assessment of life quality index among patients with acne vulgaris in a suburban population. Indian J Dermatol. 2016;61(2):163-168. doi:10.4103/0019-5154.177758
3. Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90(5):1006.e1-1006.e30. doi:10.1016/j.jaad.2023.12.017
4. Centers for Disease Control and Prevention. Outpatient antibiotic prescriptions—United States 2022. Updated November 15, 2023. Accessed July 31, 2025. https://archive.cdc.gov/www_cdc_gov/antibiotic-use/data/report-2022.html
5. Barbieri JS, Bhate K, Hartnett KP, Fleming-Dutra KE, Margolis DJ. Trends in oral antibiotic prescription in dermatology, 2008 to 2016. JAMA Dermatol. 2019;155(3):290-297. doi:10.1001/jamadermatol.2018.4944
6. Layton A. The use of isotretinoin in acne. Dermatoendocrinol. 2009;1(3):162-169. doi:10.4161/derm.1.3.9364
7. Baldwin H. Oral antibiotic treatment options for acne vulgaris. J Clin Aesthet Dermatol. 2020;13(9):26-32.
8. Moore A, Green LJ, Bruce S, et al. Once-daily oral sarecycline 1.5 mg/kg/day is effective for moderate to severe acne vulgaris: results from two identically designed, phase 3, randomized, double-blind clinical trials. J Drugs Dermatol. 2018;17(9):987-996.