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体外灰黄霉素对来自头癣患者的须癣毛癣菌分离株的抗真菌药效学特征。

In vitro pharmacodynamic characteristics of griseofulvin against dermatophyte isolates of Trichophyton tonsurans from tinea capitis patients.

机构信息

Mycology Section, Mediprobe Research Inc., London, Ontario, Canada.

出版信息

Med Mycol. 2009 Dec;47(8):796-801. doi: 10.3109/13693780802712523.

DOI:10.3109/13693780802712523
PMID:19212895
Abstract

Tinea capitis is the most commonly observed fungal infection in childhood and is primarily caused by the dermatophyte species Trichophyton tonsurans, Microsporum canis, and Trichophyton violaceum. In North America and the United Kingdom T. tonsurans is responsible for more than 90% of cases. Griseofulvin has been the treatment of choice for tinea capitis for more than 40 years and is the sole oral antifungal agent approved by the FDA for the management of tinea capitis. Some researchers have expressed concern about the possibility of emerging resistance in tinea capitis isolates, especially when there is clinical failure to treatment. A total of 151 isolates of T. tonsurans (142), M. canis (7), and T. violaceum (2) collected from tinea capitis patients were evaluated for their susceptibility to griseofulvin using the CLSI M38-A method. MIC ranges and geometric means in parenthesis were observed for T. tonsurans 0.125-16 microg/ml (1.1 microg/ml), M. canis 0.25-2 microg/ml (0.61 microg/ml), and T. violaceum 2-4 microg/ml (2.82 microg/ml), respectively. In a time kill assay with T. tonsurans UAMH 9334, 50% and 90% reduction was observed in the number of colony forming units with >2x MIC after 6 h and 12 h of exposure to the griseofulvin, respectively. Of 142 T. tonsurans isolates studied, only three could grow on SDA containing 4 times to their griseofulvin MIC, representing resistance frequencies of 1.3 x 10(-6), 6.9 x 10(-7), and 9.7 x 10(-7). Furthermore a two-fold increase in MIC was observed in isolates collected at two time intervals in only one of eight patients. Interestingly, these isolates did not show the same increase in their in vitro resistance as exhibited by the three isolated mentioned above. In light of this data, we could not confirm any correlation between increased MIC and therapy failure.

摘要

头癣是儿童中最常见的真菌感染,主要由亲动物性真菌 Trichophyton tonsurans、Microsporum canis 和 Trichophyton violaceum 引起。在北美和英国,T. tonsurans 导致的病例超过 90%。灰黄霉素作为头癣的治疗药物已经有 40 多年的历史,是 FDA 唯一批准用于治疗头癣的口服抗真菌药物。一些研究人员担心头癣分离株可能出现耐药性,尤其是在治疗失败的情况下。共评估了 151 株来自头癣患者的 T. tonsurans(142 株)、M. canis(7 株)和 T. violaceum(2 株)对头癣的药敏性,采用 CLSI M38-A 方法测定灰黄霉素的 MIC 范围和几何均数(括号内)分别为 T. tonsurans 0.125-16 μg/ml(1.1 μg/ml)、M. canis 0.25-2 μg/ml(0.61 μg/ml)和 T. violaceum 2-4 μg/ml(2.82 μg/ml)。在对头癣 UAMH 9334 的时间杀伤试验中,灰黄霉素暴露 6 小时和 12 小时后,观察到>2x MIC 时,CFU 数量分别减少 50%和 90%。在研究的 142 株 T. tonsurans 分离株中,只有 3 株可在含 4 倍灰黄霉素 MIC 的 SDA 上生长,耐药频率分别为 1.3×10(-6)、6.9×10(-7)和 9.7×10(-7)。此外,仅在 8 例患者中的 1 例中,在两个时间间隔采集的分离株中观察到 MIC 增加了两倍。有趣的是,这些分离株的体外耐药性增加与上述 3 株分离株的增加并不相同。鉴于这些数据,我们无法确认 MIC 增加与治疗失败之间存在任何相关性。

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