TOPICAL QUINOLONE OPC-7251 - A CLINICAL AND MICROBIOLOGICAL STUDY IN ACNE

Microbial hypercolonization with Propionibacterium acnes is one of the four factors in the pathogenesis of acne. Topical and systemic antibi otics play an important role in the treatment of inflammatory forms of acne. The purpose of the study was to investigate the clinical effica cy and tolerance of OPC-7251 compared with erythromycin by topical app lication in patients with papular-pustular acne. Furthermore, the anti bacterial activity of OPC-7251 against bacteria commonly found in acne vulgaris was tested in vitro by an agar dilution method. Forty-eight male and female patients were enrolled in the study from five centers. This was a double-blind, controlled, phase II study comparing efficac y and tolerability of 1% OPC-7251 cream with 2% erythromycin cream twi ce daily, for 10 weeks. Both OPC-7251 and erythromycin led to a signif icant reduction in the counts of open comedones and pustules, no stati stically significant difference between the two treatment groups was o bserved at week 10. Treatment with OPC-7251 was associated with a sign ificant reduction in the number of papules at the end of treatment com pared with baseline (p < 0.022), whereas no significant reduction was seen after treatment with erythromycin compared to baseline. Neither O PC-7251 nor erythromycin caused a significant reduction in the number of closed comedones. Safety and tolerability did not show any statisti cally significant changes in hematology, clinical chemistry or urinaly sis. Some patients in the OPC-7251 group reported pruritus and/or loca l erythema. The most common adverse events associated with erythromyci n were a warming of the skin and a local burning sensation. At week 10 , there was a statistically significant difference between the two gro ups in the minimal inhibitory concentrations (MICs) for coagulase-nega tive staphylococci (CNS) (p = 0.0012) towards the development of resis tance under erythromycin: resistance was present in five patients befo re and in all patients analyzed at the end of treatment. In contrast, none of the patients developed resistance of either CNS or P. acnes to OPC-7251. In the agar dilution test, the minimal inhibitory concentra tion (MIC(50)) was 0.25 mg/l for P. acnes, 0.125 mg/l for P. granulosu m, and 0.39 mg/l for Staph. aureus. In summary, OPC-7251, a topical qu inolone, is a new alternative for topical antibiotic treatment in acne with a low resistance potential and a clinical efficacy and safety co mparable to that of 2% erythromycin.