Although data suggest that antibiotic use by dermatologists is decreasing, our specialty still has the highest rates of oral antibiotic prescribing across all fields of medicine.1,2 In an era of intense concern about antibiotic resistance, the use of oral antibiotics in dermatology warrants careful consideration. However, the risk for resistance is just one of many potential consequences of systemic antibiotic use.
The negative and potentially prolonged impact of antibiotics on the microbiome is becoming increasingly evident. Research shows that the use of oral antibiotics reduces microbial diversity in the gut and may support an imbalance in microbial communities.3 Potential consequences of microbiome disruption are numerous and varied, ranging from increased risk for some chronic diseases to associations with certain cancers.4,5
Antibiotic use is linked to risk for Clostridium difficile infection (CDI)6 and impaired vaccine response.7 Additionally, antibiotic use is associated with risk for specific systemic side effects, including antibiotic-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis (AGEP), among others.8,9,10 These and other negative potential consequences of oral antibiotic use are outlined in the pages ahead. Importantly, this review emphasizes that detrimental effects of antibiotic use can develop even with short courses of oral treatment.
For dermatology providers, awareness of these risks should inspire a reassessment of our antibiotic prescribing habits, particularly for acne, one of the diseases for which a significant proportion of oral antibiotics are prescribed. The latest guidelines of care for the management of acne note that use of narrow-spectrum oral antibiotics and the concomitant use of topical antimicrobials like benzoyl peroxide (BPO) and/or retinoids can reduce the risk for antibiotic resistance and decrease dependence on oral agents.11
With therapeutic developments in the topical space, it may be increasingly possible to avoid altogether the use of oral antibiotics to manage acne. In fact, a recent systematic review found that the topical triple-agent fixed-dose combination clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel was one of the most efficacious and safe treatments for moderate-to-severe acne.12 A different analysis focused on treatment response within the first four weeks showed that the triple-combination gel yielded greater acne lesion reductions and rates of treatment success than did dyad combinations. Notably, research shows that bacterial cultures repeatedly exposed to the combination of clindamycin and BPO did not develop antibiotic resistance, although exposure to clindamycin alone induced resistance.13 Therefore, the triple combination formulation can be expected to present little to no risk for antibiotic resistance.
The efficacy of the fixed-dose triple combination is once again evidence that formulation science matters and vehicles matter. The moisturizing gel formulation is indicated for once daily application for the management of acne in patients 12 and older. Providing three active ingredients in a once-daily application supports therapeutic adherence. Plus, the gel formulation is well tolerated.
The availability of a triple combination, fixed-dose topical treatment for moderate-to-severe acne provides clinicians the opportunity to treat acne without relying on oral antibiotics and risking their undesirable side effects. It is well past time for prescribers to reassess their dependence on systemic antibiotics and consider effective alternatives, particularly for acne.
The negative and potentially prolonged impact of antibiotics on the microbiome is becoming increasingly evident. Research shows that the use of oral antibiotics reduces microbial diversity in the gut and may support an imbalance in microbial communities.3 Potential consequences of microbiome disruption are numerous and varied, ranging from increased risk for some chronic diseases to associations with certain cancers.4,5
Antibiotic use is linked to risk for Clostridium difficile infection (CDI)6 and impaired vaccine response.7 Additionally, antibiotic use is associated with risk for specific systemic side effects, including antibiotic-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis (AGEP), among others.8,9,10 These and other negative potential consequences of oral antibiotic use are outlined in the pages ahead. Importantly, this review emphasizes that detrimental effects of antibiotic use can develop even with short courses of oral treatment.
For dermatology providers, awareness of these risks should inspire a reassessment of our antibiotic prescribing habits, particularly for acne, one of the diseases for which a significant proportion of oral antibiotics are prescribed. The latest guidelines of care for the management of acne note that use of narrow-spectrum oral antibiotics and the concomitant use of topical antimicrobials like benzoyl peroxide (BPO) and/or retinoids can reduce the risk for antibiotic resistance and decrease dependence on oral agents.11
With therapeutic developments in the topical space, it may be increasingly possible to avoid altogether the use of oral antibiotics to manage acne. In fact, a recent systematic review found that the topical triple-agent fixed-dose combination clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel was one of the most efficacious and safe treatments for moderate-to-severe acne.12 A different analysis focused on treatment response within the first four weeks showed that the triple-combination gel yielded greater acne lesion reductions and rates of treatment success than did dyad combinations. Notably, research shows that bacterial cultures repeatedly exposed to the combination of clindamycin and BPO did not develop antibiotic resistance, although exposure to clindamycin alone induced resistance.13 Therefore, the triple combination formulation can be expected to present little to no risk for antibiotic resistance.
The efficacy of the fixed-dose triple combination is once again evidence that formulation science matters and vehicles matter. The moisturizing gel formulation is indicated for once daily application for the management of acne in patients 12 and older. Providing three active ingredients in a once-daily application supports therapeutic adherence. Plus, the gel formulation is well tolerated.
The availability of a triple combination, fixed-dose topical treatment for moderate-to-severe acne provides clinicians the opportunity to treat acne without relying on oral antibiotics and risking their undesirable side effects. It is well past time for prescribers to reassess their dependence on systemic antibiotics and consider effective alternatives, particularly for acne.
Leon Kircik MD
Clinical Professor of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Adjunct Clinical Professor of Dermatology, Indiana University School of Medicine, Indianapolis, IN; Medical Director at Physicians Skin Care, PLLC Louisville, KY; DermResearch, PLLC Louisville, KY; and Skin Sciences, PLLC Louisville, KY.
Clinical Professor of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Adjunct Clinical Professor of Dermatology, Indiana University School of Medicine, Indianapolis, IN; Medical Director at Physicians Skin Care, PLLC Louisville, KY; DermResearch, PLLC Louisville, KY; and Skin Sciences, PLLC Louisville, KY.
DISCLOSURE
Leon Kircik MD has received compensation from JDD for his editorial support.
REFERENCES
- Barbieri JS, Bhate K, Hartnett KP, et al. Trends in oral antibiotic prescription in dermatology, 2008 to 2016. JAMA Dermatol. 2019;155(3):290-297. doi:10.1001/jamadermatol.2018.4944.
- MacGibeny MA, Jo JH, Kong HH. Antibiotic stewardship in dermatology-reducing the risk of prolonged antimicrobial resistance in skin. JAMA Dermatol. 2022;158(9):989-991. doi:10.1001/jamadermatol.2022.3168.
- Dethlefsen L, et al. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6(11):E280.
- Queen J, Zhang J, Sears CL. Oral antibiotic use and chronic disease: long-term health impact beyond antimicrobial resistance and Clostridioides difficile. Gut Microbes. 2020;11(4):1092-1103.
- Chen J, Domingue JC, Sears CL. Microbiota dysbiosis in select human cancers: evidence of association and causality. Semin Immunol. 2017;32:25-34.
- Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015;372(16):1539-1548.
- Chapman TJ, et al. Antibiotic use and vaccine antibody levels. Pediatrics. 2022;149(5).
- Sharifzadeh S, et al. Antibacterial antibiotic-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a literature review. Eur J Clin Pharmacol. 2021;77(3):275-289.
- Mockenhaupt M. The current understanding of Stevens-Johnson syndrome and toxic epidermal necrolysis. Expert Rev Clin Immunol. 2011;7(6):803-813; quiz 814-815.
- Sidoroff A, et al. Acute generalized exanthematous pustulosis (AGEP)--a clinical reaction pattern. J Cutan Pathol. 2001;28(3):113-119.
- 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.
- Harper JC, Baldwin H, Choudhury SP, et al. Treatments for moderate-to-severe acne vulgaris: a systematic review and network meta-analysis. J Drugs Dermatol. 2024;23(4):216-226. doi:10.36849/JDD.8148.
- Ghannoum M, Gamal A, Kadry A, et al. Criticality of benzoyl peroxide and antibiotic fixed combinations in combating rising resistance in Cutibacterium acnes. Clin Cosmet Investig Dermatol. 2025;18:755-766.
