Clinical Review & Education

JAMA Dermatology Clinical Evidence Synopsis

Antibiotic Resistance in Acne Treatment

Brandon L. Adler, MD; Heather Kornmehl, BS; April W. Armstrong, MD, MPH

CLINICAL QUESTION What is the evidence for antibiotic resistance in acne, and how does
resistance affect treatment?

BOTTOM LINE Use of topical and systemic antibiotics for acne is associated with formation
of resistance in Propionibacterium acnes and other bacteria, with clinical consequences.
Guidelines recommend resistance reduction strategies including avoidance of antibiotic
monotherapy, combination treatment with topical modalities, and limiting the duration of
oral antibiotic use.

Introduction The clinical efficacy of topical erythromycin decreased from the

Antibiotics are a fundamental component of the treatment of acne
owing to the role that Propionibacterium acnes plays in its patho-
genesis. Despite a relatively small workforce, dermatologists dis-
proportionately prescribe antibiotics.1 However, antibiotic resis-
tance is a global issue with increasing prevalence over time. The
antibiotics most frequently used for acne are topical erythromycin
and clindamycin and oral tetracyclines, which are bacteriostatic
(inhibiting bacterial growth) rather than bactericidal (killing bacte-
ria). Exposure to bacteriostatic agents may encourage the emer-
gence of antibiotic-resistant strains of P acnes.
Summary of Findings
Use of antibiotics for acne is associated with development of resis-
tance in P acnes, mostly via point mutations.1
Multiple countries report resistance in greater than half of P ac-
nes isolates, predominantly to topical erythromycin and clinda-
mycin, and less so to tetracyclines.1,2
Evidence Profile
No. of trials: 5
No. of randomized clinical trials: 0
Study years: 1987-2002, 2007-2008
No. of patients: 120 088
Male: 44.1% Female: 55.9%
Race: White (65.6%) (from 2 trials [662 participants])
Age, mean (range): 22.3 (12-59) years
Setting: Outpatient
Countries: United States (n = 3), United Kingdom (n = 2), Greece,
Hungary, Italy, Spain, Sweden (n = 1 each)
Primary outcomes:
Prevalence of antibiotic-resistant Propionibacterium acnes
among patients and untreated contacts
Nasal/pharyngeal colonization with Staphylococcus aureus and
antibiotic susceptibility patterns
Diagnosis of upper respiratory or urinary tract infection
Self-reported pharyngitis
Secondary outcomes: Genotypic/phenotypic analysis of resistant
P acnes
1970s to 2002, attributed to antibiotic resistance.1
Resistant P acnes is found on the skin of untreated contacts of acne
patients prescribed antibiotics.2 Resistant strains of P acnes are
reported to cause severe infections1; therefore, current prescrib-
ing practices may represent a risk to untreated contacts, espe-
cially those with impaired immunity.
After discontinuation of therapy, resistance may persist.1
Although P acnes is not known to acquire resistance from or
transfer it to other bacteria,1 using antibiotics for acne leads to
off-target effects.
Use of topical antibiotics is associated with resistance in Staphy-
lococcus aureus. This organism, especially when methicillin resis-
tant, is responsible for potentially severe health care and com-
munity-associated infections. Treatment with oral tetracyclines is
associated with lower S aureus carriage rates, without increased
resistance.3
In a retrospective cohort of more than 100 000 patients with
acne, those treated with topical and/or oral antibiotics for at
least 6 weeks were significantly more likely to develop upper
respiratory infections during 1 year of follow-up than patients
who had not received antibiotics (odds ratio, 2.15; 95% CI, 2.05-
2.23; P < .001).4
In a prospective cohort of university students (N = 579), those re-
ceiving oral antibiotics for acne were more than 4 times more likely
to report pharyngitis during 1 year of follow-up than untreated
individuals (odds ratio, 4.34; 95% CI, 1.51-12.47).5
Discussion
Current Guidelines
Lack of development of new antibiotics and increasing resistance
rates have prompted an emphasis on antibiotic stewardship in acne
treatment guidelines (Table). The American Academy of Derma-
tologys most recent guidelines6 recommend coadministration of
benzoyl peroxide (BP), a topical bactericidal agent not reported to
cause resistance, alongside both topical and oral antibiotics. Ben-
zoyl peroxide is comedolytic and kills P acnes by generating free radi-
cals. Added to topical antibiotics, BP may prevent the formation of
resistance and increase treatment efficacy. Only indirect evidence
supports the ability of BP to limit resistance when used with oral
antibiotics.7

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 Clinical Review & Education JAMA Dermatology Clinical Evidence Synopsis

For moderate-to-severe acne, first-line treatment is with oral

Table. Guidelines for Treatment of Acne With Antibiotics
antibiotics combined with BP and a topical retinoid. Oral antibi-
Strength of
Treatment Recommendation
otic monotherapy is not recommended. Topical antibiotics may
American Academy of Dermatology Guidelines6 also be included in the regimen, provided BP is used concomi-
Mild-to-moderate acne
tantly. The first-line oral antibiotics are doxycycline and minocy-
cline, which exert anti-inflammatory as well as antimicrobial
BP A
effects. Because of associated resistance, systemic erythromycin
Topical retinoid A
should be avoided, except in patients unable to tolerate tetracy-
BP + topical retinoid A
cline therapy (eg, pregnant women and children <8 years old);
BP + topical antibiotic A
trimethoprim-sulfamethoxazole may also be considered. Dura-
BP + topical retinoid + topical antibiotic A tion of therapy should preferably be limited to 3 to 4 months. To
Moderate-to-severe acne facilitate this, BP and topical retinoids should be continued as
Oral antibiotic + BP + topical retinoid A maintenance therapy after discontinuation of systemic antibiotic
Oral antibiotic + BP + topical antibiotic A treatment. There is no guideline addressing retreatment with oral
Oral antibiotic + BP + topical retinoid + topical A antibiotics for flares subsequent to the initial course. Patients
antibiotic who require longer treatment courses with oral antibiotics should
European Guidelines7
be closely observed to limit use to the shortest possible duration.
Mild-to-moderate acne The European Evidence-Based Guideline for the Treatment of
Fixed-dose BP/topical retinoid High Acne7 also advises against topical or systemic antibiotic mono-
Fixed-dose BP/topical antibiotic High therapy and recommends limiting the duration of systemic antibi-
BP Medium otics to 3 months but diverges from American Academy of Derma-
Topical retinoid Medium tology guidelines regarding combination treatment. For mild-to-
Fixed-dose topical antibiotic/retinoid Medium moderate acne, fixed-dose topical antibiotic/retinoid may be used,
Azelaic acid Medium without BP. For moderate-to-severe acne, oral antibiotics may be
Moderate-to-severe acne
combined with topical retinoids, fixed-dose topical retinoid/BP, or
azelaic acid. There is a lower strength of recommendation for the
Oral antibiotic + topical retinoid Medium
combination of oral antibiotics and BP.
Oral antibiotic + fixed-dose BP/retinoid Medium
Oral antibiotic + azelaic acid Medium
Limitations and Areas in Need of Further Study
Oral antibiotic + BP Low The body of data on antibiotic resistance in acne is limited in scope
Abbreviation: BP, benzoyl peroxide. and quality. Additional studies are needed to address multiple
evidence gaps. Reduction of resistance through use of BP and fixed-
dose topical formulations should be quantified by susceptibility test-
For mild-to-moderate acne, first-line treatment is with BP, ing and genomic studies to more completely elucidate the benefits
topical retinoids, or combination therapy, which may incorporate of combination therapy. It is unclear how effectively adding BP to
a topical antibiotic (BP + antibiotic, BP + retinoid, BP + antibi- systemic antibiotics impedes resistance formation, contrasting
otic + retinoid). Topical antibiotic monotherapy is not recom- the limited application of BP with the antibiotics distribution
mended. In patients who benefit from topical antibiotic treatment, throughout the body. Subantimicrobial antibiotic dosing, which may
available fixed-combination antibiotic/BP formulations simplify the discourage resistance, is still poorly understood and merits further
regimen and potentially improve patient adherence. inquiry.

ARTICLE INFORMATION
Author Affiliations: Department of Dermatology,
Keck School of Medicine, University of Southern
California, Los Angeles (Adler, Armstrong); Drexel
University College of Medicine, Philadelphia,
Pennsylvania (Kornmehl).
Corresponding Author: April W. Armstrong, MD,
MPH, Department of Dermatology, Keck School of
Medicine, University of Southern California, 1975
Zonal Ave, KAM 510, MC 9034, Los Angeles, CA
90089 (aprilarmstrong@post.harvard.edu).
Published Online: June 21, 2017.
doi:10.1001/jamadermatol.2017.1297
Conflict of Interest Disclosures: Dr Armstrongs
disclosures include serving as an investigator and
consultant/advisor to AbbVie, Celgene, Janssen,
Lilly, Novartis, Sanofi, Regeneron, Pfizer, and
Modernizing Medicine, none relevant to this
manuscript. No other disclosures are reported.
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