Browsing by Author "Harper, Julie C."

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    Criticality of Benzoyl Peroxide and Antibiotic Fixed Combinations in Combating Rising Resistance in Cutibacterium acnes
    (Dove Press, 2025-03-31) Ghannoum, Mahmoud; Gamal, Ahmed; Kadry, Ahmed; Del Rosso, James Q.; Stein Gold, Linda; Kircik, Leon H.; Harper, Julie C.; Dermatology, School of Medicine
    Background: Antibiotic resistance is growing globally, with multiple countries reporting resistance in >50% of Cutibacterium acnes (C. acnes) strains. Combination formulations of an antibiotic and the antimicrobial benzoyl peroxide (BPO) may reduce this resistance risk, especially with prolonged use. This 4-part study tested susceptibility of 31 C. acnes clinical strains and development of resistance to antibiotics alone or combined with BPO. Methods: C. acnes susceptibility to single-drug antibiotics was assessed via minimum inhibitory concentration (MIC) values obtained from epsilometer tests, with lower MIC indicating higher susceptibility. Susceptibility to fixed-dose antibiotic/BPO combination products was determined by measuring the zone of inhibition using the agar diffusion method, with larger diameter indicating increased bacterial inhibition. The effect (synergistic, additive, antagonistic, or indifferent [no interaction]) of combining clindamycin with BPO on C. acnes inhibition was evaluated using a checkerboard assay, wherein 2 test compounds are combined in varying concentrations. Resistance development was assessed using serial passage of bacterial cultures in increasing concentrations of clindamycin alone or in combination with BPO. Results: All tested antibiotics (clindamycin, doxycycline, erythromycin, and minocycline) exhibited similar activity. C. acnes susceptibility was variable, with some strains having elevated MIC values-an indication of resistance-against different antibiotics. For 6 strains resistant to clindamycin alone (inhibitory zone=0 cm), formulations with BPO enhanced activity against the same isolates (range: 0.8-2.2 cm). Of 7 acne-associated strains, combining clindamycin and BPO had an additive effect against 4, and no interaction against 3. Bacterial cultures repeatedly exposed to the combination of clindamycin and BPO did not develop antibiotic resistance, which occurred with exposure to clindamycin alone. Conclusion: Overall, antibiotic susceptibility was highly dependent on the C. acnes strain, and antibiotic formulations with BPO exhibited enhanced activity against less susceptible strains. Fixed combinations of BPO with an antibiotic may improve antimicrobial activity and protect against resistance development.
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    Efficacy and Safety of Fixed-dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel in Black Participants with Moderate to Severe Acne
    (Matrix Medical Communications, 2025) Callender, Valerie D.; Alexis, Andrew F.; Bhatia, Neal; Harper, Julie C.; Baldwin, Hilary; Guenin, Eric; Kircik, Leon H.; Dermatology, School of Medicine
    Objective: Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel-the only approved fixed-dose, triple-combination acne treatment-demonstrated superior efficacy to vehicle and component dyads, with favorable safety/tolerability in Phase 2 and Phase 3 studies. In order to examine efficacy and safety of CAB in patients with darker skin phototypes, a post hoc analysis of clinical trial data of participants who self-identified as "Black or African American" was conducted. Methods: Data were pooled from two Phase 2 and two Phase 3, double-blind, 12-week studies (NCT03170388, NCT04892706, NCT04214639, NCT04214652). Eligible participants aged ≥9 years (≥12 years in NCT04892706) were randomized to once-daily CAB or vehicle. Endpoints included ≥2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and inflammatory/noninflammatory lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were also assessed. Results: Of 1,115 participants randomized to CAB or vehicle, 156 (14%) were Black. At Week 12, 32.0 percent of CAB-treated participants achieved treatment success versus 18.3 percent with vehicle (P=0.07). Inflammatory and noninflammatory lesion reductions were significantly greater with CAB versus vehicle (68.8% vs. 51.4% and 57.8% vs. 45.5%, respectively; P<0.05, both). TEAE severity was mild to moderate, and hyperpigmentation mean scores remained at/below baseline value (0.7; 1=mild). Limitations: Studies were not powered to detect significant differences between CAB and vehicle for Black participants; therefore, P values are for informative purposes only. Conclusion: CAB gel was efficacious and well tolerated in Black participants with acne.