Assessing Cutibacterium Acnes Susceptibility With Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel Use: Six-Month Analysis
November 2025 | Volume 24 | Issue 11 | 9213 | Copyright © November 2025
Published online October 8, 2025
Mahmoud Ghannoum PhDa,b, Ahmed Eltokhy MDa, James Sewake BSa, Thomas McCormick PhDa, Neal Bhatia MDc, Hilary Baldwin MDd,e, Linda Stein Gold MDf, Julie C. Harper MDg, Joshua A. Zeichner MDh, Edward (Ted) Lain MD MBAi, Valerie D. Callender MDj,k, Eric Guenin PharmD, PhD MPHl, Zoe D. Draelos MDm
aDepartment of Dermatology, Case Western Reserve University, School of Medicine, Cleveland, OH
bCenter for Medical Mycology, University Hospitals Cleveland Medical Center, Cleveland, OH
cTherapeutics Clinical Research, San Diego, CA
dThe Acne Treatment and Research Center, Brooklyn, NY
eDepartment of Dermatology, Robert Wood Johnson University Hospital, New Brunswick, NJ
fDepartment of Dermatology, Henry Ford Hospital, Detroit, MI
gDermatology & Skin Care Center of Birmingham, Birmingham, AL
hDepartment of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY
iAustin Institute for Clinical Research, Austin, TX
jCallender Dermatology and Cosmetic Center, Glenn Dale, MD
kDepartment of Dermatology, Howard University College of Medicine, Washington, DC
lOrtho Dermatologics,* Bridgewater, NJ
mDermatology Consulting Services, High Point, NC
Abstract
Background: The only approved triple-combination acne treatment – clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel - demonstrated efficacy/safety in 12-week clinical trials. However, real-world treatment may require 6 months for maximum benefits in some cases. Since long-term antibiotic use can lead to resistance in the causative Cutibacterium acnes (C. acnes), this analysis evaluated the effect of long-term CAB use on C. acnes.
Methods: Pooled data from 2 identical, 24-week, single-center, open-label studies evaluated once-daily CAB in participants aged
≥12 years with moderate/severe acne (Investigator's Global Assessment [IGA] of 3/4). Plates inoculated with central forehead swabs were monitored for C. acnes colony formation. Clindamycin susceptibility was assessed via minimum inhibitory concentration (MIC) values using Epsilometer tests; MIC ≥8 μg/mL indicated resistance.
Results: Of 50 participants enrolled, 45 completed the studies. At baseline, C. acnes strains were isolated from 82% (37/45) of participants. After 24 weeks, CAB-treated participants with cultivable isolates decreased by nearly half to 44% (20/45). For susceptible strains isolated at week 24, MIC values remained low (mean, 0.19 μg/mL). Only 1 participant without growth at baseline had cultivable C. acnes at week 24, deemed clindamycin-susceptible. Only the 5 participants (11%) with resistant C. acnes isolates at baseline had resistant isolates at study end, though all 5 had acne improvements at week 24 (IGA decrease, 1-3 points; lesion reductions, 40%-100%).
Conclusions: Long-term CAB gel treatment did not lead to antibiotic resistance development and was efficacious in participants with resistant isolates at baseline, suggesting CAB is well suited for long-term acne treatment.
INTRODUCTION
Topical therapies such as antibiotics are a mainstay of acne treatment.1 However, one concern with the long-term use of antibiotic-containing formulations is the development of antibiotic resistance in the causative bacterium Cutibacterium acnes (C. acnes). There are multiple consequences of antibiotic resistance in C. acnes, including increased acne therapeutic failure, potential for the transfer of resistance genes from C. acnes to other pathogenic bacterial strains, and therapeutic failure in other pathological conditions driven by C. acnes including sarcoidosis and infective endocarditis.2-6
The concomitant use of benzoyl peroxide (BPO) with topical antibiotics has been shown to prevent antibiotic resistance.7 As an antimicrobial, BPO is directly toxic to C. acnes and therefore effective at reducing C. acnes populations.8,9 Additionally, to date, no C. acnes resistance to BPO has been reported in
