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Path of Least Resistance: Guidance for Antibiotic Stewardship in Acne
Dermatologists have long relied on oral antibiotics to manage moderate to severe acne1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.5 The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.
In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.
MECHANISMS OF RESISTANCE IN ACNE THERAPY
Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.5 These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.
PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE
The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.10 This practical framework supports safe, effective, and streamlined prescribing.
Reserve Oral Antibiotics for Appropriate Cases
Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.
Combine Oral Antibiotics With Topical Retinoids
Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.
Consider Adding an Adjunctive Topical Antimicrobial Agent
Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.
Limit Treatment Duration to 12 Weeks or Less
Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.
Simplify Treatment Regimens to Enhance Adherence
Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.13,14
Select Narrower-Spectrum Antibiotics When Feasible
Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.
Use Systemic Nonantibiotic Therapies When Appropriate
If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.
FINAL THOUGHTS
Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.
- Bhate K, Williams H. Epidemiology of acne vulgaris. Br J Dermatol. 2013;168:474-485.
- Barbieri JS, Bhate K, Hartnett KP, et al. Trends in oral antibiotic prescription in dermatology, 2008 to 2016. JAMA Dermatol. 2019;155:290-297.
- Grada A, Armstrong A, Bunick C, et al. Trends in oral antibiotic use for acne treatment: a retrospective, population-based study in the United States, 2014 to 2016. J Drugs Dermatol. 2023;22:265-270.
- Perche PO, Peck GM, Robinson L, et al. Prescribing trends for acne vulgaris visits in the United States. Antibiotics. 2023;12:269.
- Karadag A, Aslan Kayıran M, Wu CY, et al. Antibiotic resistance in acne: changes, consequences and concerns. J Eur Acad Dermatol Venereol. 2021;35:73-78.
- Eady AE, Cove JH, Layton AM. Is antibiotic resistance in cutaneous propionibacteria clinically relevant? implications of resistance for acne patients and prescribers. Am J Clin Dermatol. 2003;4:813-831.
- Eady EA, Cove J, Holland K, et al. Erythromycin resistant propionibacteria in antibiotic treated acne patients: association with therapeutic failure. Br J Dermatol. 1989;121:51-57.
- Grossman TH. Tetracycline antibiotics and resistance. Cold Spring Harb Perspect Med. 2016;6:a025387.
- Kayiran M AS, Karadag AS, Al-Khuzaei S, et al. Antibiotic resistance in acne: mechanisms, complications and management. Am J Clin Dermatol. 2020;21:813-819.
- Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90:1006-1035.
- Kucera K, Zenzola N, Hudspeth A, et al. Benzoyl peroxide drug products form benzene. Environ Health Perspect. 2024;132:037702.
- Kucera K, Zenzola N, Hudspeth A, et al. Evaluation of benzene presence and formation in benzoyl peroxide drug products. J Invest Dermatol. 2025;145:1147-1154.E11.
- Grada A, Perche P, Feldman S. Adherence and persistence to acne medications: a population-based claims database analysis. J Drugs Dermatol. 2022;21:758-764.<.li>
- Anderson KL, Dothard EH, Huang KE, et al. Frequency of primary nonadherence to acne treatment. JAMA Dermatol. 2015;151:623-626.
- Grada A, Bunick CG. Spectrum of antibiotic activity and its relevance to the microbiome. JAMA Netw Open. 2021;4:E215357-E215357.
- Francino M. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front Microbiol. 2016;6:164577.
- Moura IB, Grada A, Spittal W, et al. Profiling the effects of systemic antibiotics for acne, including the narrow-spectrum antibiotic sarecycline, on the human gut microbiota. Front Microbiol. 2022;13:901911.
- Zhanel G, Critchley I, Lin L-Y, et al. Microbiological profile of sarecycline, a novel targeted spectrum tetracycline for the treatment of acne vulgaris. Antimicrob Agents Chemother. 2019;63:1297-1318.
Dermatologists have long relied on oral antibiotics to manage moderate to severe acne1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.5 The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.
In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.
MECHANISMS OF RESISTANCE IN ACNE THERAPY
Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.5 These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.
PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE
The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.10 This practical framework supports safe, effective, and streamlined prescribing.
Reserve Oral Antibiotics for Appropriate Cases
Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.
Combine Oral Antibiotics With Topical Retinoids
Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.
Consider Adding an Adjunctive Topical Antimicrobial Agent
Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.
Limit Treatment Duration to 12 Weeks or Less
Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.
Simplify Treatment Regimens to Enhance Adherence
Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.13,14
Select Narrower-Spectrum Antibiotics When Feasible
Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.
Use Systemic Nonantibiotic Therapies When Appropriate
If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.
FINAL THOUGHTS
Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.
Dermatologists have long relied on oral antibiotics to manage moderate to severe acne1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.5 The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.
In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.
MECHANISMS OF RESISTANCE IN ACNE THERAPY
Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.5 These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.
PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE
The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.10 This practical framework supports safe, effective, and streamlined prescribing.
Reserve Oral Antibiotics for Appropriate Cases
Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.
Combine Oral Antibiotics With Topical Retinoids
Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.
Consider Adding an Adjunctive Topical Antimicrobial Agent
Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.
Limit Treatment Duration to 12 Weeks or Less
Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.
Simplify Treatment Regimens to Enhance Adherence
Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.13,14
Select Narrower-Spectrum Antibiotics When Feasible
Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.
Use Systemic Nonantibiotic Therapies When Appropriate
If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.
FINAL THOUGHTS
Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.
- Bhate K, Williams H. Epidemiology of acne vulgaris. Br J Dermatol. 2013;168:474-485.
- Barbieri JS, Bhate K, Hartnett KP, et al. Trends in oral antibiotic prescription in dermatology, 2008 to 2016. JAMA Dermatol. 2019;155:290-297.
- Grada A, Armstrong A, Bunick C, et al. Trends in oral antibiotic use for acne treatment: a retrospective, population-based study in the United States, 2014 to 2016. J Drugs Dermatol. 2023;22:265-270.
- Perche PO, Peck GM, Robinson L, et al. Prescribing trends for acne vulgaris visits in the United States. Antibiotics. 2023;12:269.
- Karadag A, Aslan Kayıran M, Wu CY, et al. Antibiotic resistance in acne: changes, consequences and concerns. J Eur Acad Dermatol Venereol. 2021;35:73-78.
- Eady AE, Cove JH, Layton AM. Is antibiotic resistance in cutaneous propionibacteria clinically relevant? implications of resistance for acne patients and prescribers. Am J Clin Dermatol. 2003;4:813-831.
- Eady EA, Cove J, Holland K, et al. Erythromycin resistant propionibacteria in antibiotic treated acne patients: association with therapeutic failure. Br J Dermatol. 1989;121:51-57.
- Grossman TH. Tetracycline antibiotics and resistance. Cold Spring Harb Perspect Med. 2016;6:a025387.
- Kayiran M AS, Karadag AS, Al-Khuzaei S, et al. Antibiotic resistance in acne: mechanisms, complications and management. Am J Clin Dermatol. 2020;21:813-819.
- Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90:1006-1035.
- Kucera K, Zenzola N, Hudspeth A, et al. Benzoyl peroxide drug products form benzene. Environ Health Perspect. 2024;132:037702.
- Kucera K, Zenzola N, Hudspeth A, et al. Evaluation of benzene presence and formation in benzoyl peroxide drug products. J Invest Dermatol. 2025;145:1147-1154.E11.
- Grada A, Perche P, Feldman S. Adherence and persistence to acne medications: a population-based claims database analysis. J Drugs Dermatol. 2022;21:758-764.<.li>
- Anderson KL, Dothard EH, Huang KE, et al. Frequency of primary nonadherence to acne treatment. JAMA Dermatol. 2015;151:623-626.
- Grada A, Bunick CG. Spectrum of antibiotic activity and its relevance to the microbiome. JAMA Netw Open. 2021;4:E215357-E215357.
- Francino M. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front Microbiol. 2016;6:164577.
- Moura IB, Grada A, Spittal W, et al. Profiling the effects of systemic antibiotics for acne, including the narrow-spectrum antibiotic sarecycline, on the human gut microbiota. Front Microbiol. 2022;13:901911.
- Zhanel G, Critchley I, Lin L-Y, et al. Microbiological profile of sarecycline, a novel targeted spectrum tetracycline for the treatment of acne vulgaris. Antimicrob Agents Chemother. 2019;63:1297-1318.
- Bhate K, Williams H. Epidemiology of acne vulgaris. Br J Dermatol. 2013;168:474-485.
- Barbieri JS, Bhate K, Hartnett KP, et al. Trends in oral antibiotic prescription in dermatology, 2008 to 2016. JAMA Dermatol. 2019;155:290-297.
- Grada A, Armstrong A, Bunick C, et al. Trends in oral antibiotic use for acne treatment: a retrospective, population-based study in the United States, 2014 to 2016. J Drugs Dermatol. 2023;22:265-270.
- Perche PO, Peck GM, Robinson L, et al. Prescribing trends for acne vulgaris visits in the United States. Antibiotics. 2023;12:269.
- Karadag A, Aslan Kayıran M, Wu CY, et al. Antibiotic resistance in acne: changes, consequences and concerns. J Eur Acad Dermatol Venereol. 2021;35:73-78.
- Eady AE, Cove JH, Layton AM. Is antibiotic resistance in cutaneous propionibacteria clinically relevant? implications of resistance for acne patients and prescribers. Am J Clin Dermatol. 2003;4:813-831.
- Eady EA, Cove J, Holland K, et al. Erythromycin resistant propionibacteria in antibiotic treated acne patients: association with therapeutic failure. Br J Dermatol. 1989;121:51-57.
- Grossman TH. Tetracycline antibiotics and resistance. Cold Spring Harb Perspect Med. 2016;6:a025387.
- Kayiran M AS, Karadag AS, Al-Khuzaei S, et al. Antibiotic resistance in acne: mechanisms, complications and management. Am J Clin Dermatol. 2020;21:813-819.
- Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90:1006-1035.
- Kucera K, Zenzola N, Hudspeth A, et al. Benzoyl peroxide drug products form benzene. Environ Health Perspect. 2024;132:037702.
- Kucera K, Zenzola N, Hudspeth A, et al. Evaluation of benzene presence and formation in benzoyl peroxide drug products. J Invest Dermatol. 2025;145:1147-1154.E11.
- Grada A, Perche P, Feldman S. Adherence and persistence to acne medications: a population-based claims database analysis. J Drugs Dermatol. 2022;21:758-764.<.li>
- Anderson KL, Dothard EH, Huang KE, et al. Frequency of primary nonadherence to acne treatment. JAMA Dermatol. 2015;151:623-626.
- Grada A, Bunick CG. Spectrum of antibiotic activity and its relevance to the microbiome. JAMA Netw Open. 2021;4:E215357-E215357.
- Francino M. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front Microbiol. 2016;6:164577.
- Moura IB, Grada A, Spittal W, et al. Profiling the effects of systemic antibiotics for acne, including the narrow-spectrum antibiotic sarecycline, on the human gut microbiota. Front Microbiol. 2022;13:901911.
- Zhanel G, Critchley I, Lin L-Y, et al. Microbiological profile of sarecycline, a novel targeted spectrum tetracycline for the treatment of acne vulgaris. Antimicrob Agents Chemother. 2019;63:1297-1318.
Path of Least Resistance: Guidance for Antibiotic Stewardship in Acne
Path of Least Resistance: Guidance for Antibiotic Stewardship in Acne
Practice Point
- Oral antibiotics remain a cornerstone in the treatment of moderate to severe acne, but growing concerns about antibiotic resistance necessitate more intentional prescribing.
