In Vitro Activities of Azole Antifungal Agents against Propionibacterium acnes Isolated from Patients with Acne Vulgaris

Abstract

Propionibacterium acnes is a Gram-positive anaerobic to aero-tolerant bacterium and part of the skin microbiota in humans. It colonizes areas of skin rich in sebaceous glands, such as the scalp and face. The amount of P. acnes in skin is related to the activity of the sebaceous glands; the population increases after the maturation of sebaceous gland function following puberty. 1)P. acnes is the major etiological agent of inflammatory acne, and multiple mechanisms are involved in this inflammatory process. P. acnes stimulates the release of interleukin-1 (IL-1), IL-8, and tumor necrosis factor-a (TNF-a) and activates the complement system. This microorganism also produces free fatty acids via the hydrolysis of sebaceous gland triglycerides by its lipase. A wide range of antibiotic classes are effective against acne vulgaris due to P. acnes, such as clindamycin, erythromycin, quinolones, and the tetracycline family. In the last decade, the appearance of antibiotic-resistant P. acnes has increased.2) A European surveillance study suggested that 15.1% of clinical isolates were resistant to clindamycin and 17.1% to erythromycin. 3)In the 1980s, a double-blind trial of a lotion containing 2% miconazole (MCZ) and 5% benzoyl peroxide was performed in patients with acne vulgaris. 4) High efficacy was seen in 88% of the combination group compared to the group using benzoyl peroxide alone, with a significant reduction in inflammatory lesions. Although MCZ is an imidazole antifungal agent, the compound is also active against Gram-positive bacteria, such as P. acnes, Staphylococcus aureus, and Corynebacterium spp. in vitro.5) The compound causes the release of cellular K ϩ , which may be related to membrane damage.6,7) More than 20 years have passed since the clinical effectiveness of MCZ against acne vulgaris due to P. acnes was first elucidated. Since then, several azole agents have been introduced for the clinical treatment of fungal infections. In this study, we reassessed the in vitro activities of several azole antifungal agents against P. acnes. MATERIALS AND METHODSMaterials Thirty-two clinical P. acnes isolates were obtained from patients with acne vulgaris. Of them, eight were resistant to both erythromycin [minimum inhibitory concentration (MIC), 8-16 mg/ml] and clindamycin (MIC, 32-64 mg/ml), while all were susceptible to penicillin G (MIC, Ͻ0.25 mg/ml), ampicillin (MIC, Ͻ0.25 mg/ml), piperacillin (MIC, Ͻ8 mg/ml), cefozopran (MIC, Ͻ4 mg/ml), cefmetazole (MIC, Ͻ4 mg/ml), latamoxef (MIC, Ͻ4 mg/ml), imipenem/ cilastatin (MIC, 1 mg/ml), clindamycin (MIC, 0.5 mg/ml), minocycline (MIC, Ͻ1 mg/ml), chloramphenicol (MIC, 4 mg/ml), and tosufloxacin (MIC, Ͻ0.5-1 mg/ml). MCZ, fluconazole (FLZ), itraconazole (ITZ), and voriconazole (VRZ) were purchased from ASTY (Kyokuto Pharmaceutical, Tokyo, Japan); ketoconazole (KTZ) was obtained from Jassen Pharmaceutical (Tokyo, Japan).Drug Susceptibility Testing The in vitro activities of the five azole agents were determined at concentrations of 0.125-8 mg/ml in reduced Brucella broth ...

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