Ghannoum Mahmoud, Gamal Ahmed, Kadry Ahmed, Del Rosso James Q, Stein Gold Linda, Kircik Leon H, Harper Julie C
Department of Dermatology, Case Western Reserve University, Cleveland, OH, USA.
University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Clin Cosmet Investig Dermatol. 2025 Mar 31;18:755-766. doi: 10.2147/CCID.S506254. eCollection 2025.
Antibiotic resistance is growing globally, with multiple countries reporting resistance in >50% of () 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 clinical strains and development of resistance to antibiotics alone or combined with BPO.
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 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.
All tested antibiotics (clindamycin, doxycycline, erythromycin, and minocycline) exhibited similar activity. 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.
Overall, antibiotic susceptibility was highly dependent on the 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.
全球抗生素耐药性不断增加，多个国家报告称超过50%的（）菌株存在耐药性。抗生素与抗菌剂过氧化苯甲酰（BPO）的联合制剂可能会降低这种耐药风险，尤其是长期使用时。这项分为四个部分的研究测试了31株临床菌株对单独使用抗生素或与BPO联合使用时的敏感性以及耐药性的产生情况。
通过从梯度扩散法获得的最低抑菌浓度（MIC）值评估对单一药物抗生素的敏感性，MIC值越低表明敏感性越高。通过使用琼脂扩散法测量抑菌圈来确定对固定剂量抗生素/BPO联合产品的敏感性，抑菌圈直径越大表明细菌抑制作用增强。使用棋盘法评估克林霉素与BPO联合对（）抑制的效果（协同、相加、拮抗或无关[无相互作用]），其中将两种测试化合物以不同浓度组合。通过在单独或与BPO联合使用的浓度不断增加的克林霉素中连续传代细菌培养物来评估耐药性的产生情况。
所有测试的抗生素（克林霉素、多西环素、红霉素和米诺环素）表现出相似的活性。（）敏感性各不相同，一些菌株对不同抗生素的MIC值升高——这表明存在耐药性。对于6株单独对克林霉素耐药的菌株（抑菌圈 = 0厘米），含BPO的制剂增强了对相同分离株的活性（范围：0.8 - 2.2厘米）。在7株与痤疮相关的菌株中，克林霉素和BPO联合对4株有相加作用，对3株无相互作用。反复暴露于克林霉素和BPO联合制剂的细菌培养物未产生抗生素耐药性，而单独暴露于克林霉素时则会产生耐药性。
总体而言，抗生素敏感性高度依赖于（）菌株，含BPO的抗生素制剂对敏感性较低的菌株表现出增强的活性。BPO与抗生素的固定组合可能会提高抗菌活性并防止耐药性的产生。
