几种抗真菌药物对马尔尼菲青霉的体外药敏试验

目的 观察马尔尼菲青霉（PM）广西野生银星竹鼠寄生株与临床人分离株对伏立康唑和几种常用抗真菌药物的敏感性。方法 采用美国临床实验室标准委员会（CLSI）M27-A2和M38-A方案中的微量稀释法，测定伏立康唑、伊曲康唑、特比萘芬、两性霉素B 及氟康唑对14株广西野生银星竹鼠PM寄生株与25株临床人PM分离株25 ℃菌丝相及37 ℃酵母相的最小抑菌浓度（MIC）。用两样本均数比较t检验比较PM寄生株与临床人PM分离株MIC的差异性，用配对t检验比较同一株菌在两种不同温度相下的MIC差异性。结果 伏立康唑、伊曲康唑、特比萘芬、两性霉素B、氟康唑对PM寄生株菌丝相的MIC分别为：0.0313 ～ 0.1250、0.1250 ～ 1.0000、0.0313 ～ 0.5000、0.2500 ～ 4.0000、2.0000 ～ 8.0000 mg/L；对PM寄生株酵母相的MIC分别为：0.0078 ～ 0.2500、0.0313 ～ 0.5000、0.0313 ～ 1.0000、0.2500 ～ 2.0000、1.0000 ～ 8.0000 mg/L；对PM临床人分离株菌丝相的MIC分别为：0.0313 ～ 0.2500、0.0625 ～ 1.0000、0.0313 ～ 1.0000、0.2500 ～ 4.0000、2.0000 ～ 32.0000 mg/L；对PM临床人分离株酵母相的MIC分别为：0.0039 ～ 0.2500、0.0313 ～ 0.5000、0.0313 ～ 2.0000、0.1250 ～ 2.0000、2.0000 ～ 16.0000 mg/L。5种抗真菌药物对广西野生银星竹鼠PM寄生株与临床人PM分离株菌丝相和酵母相均敏感。同一温度下伏立康唑对两种不同来源PM的MIC最低，其他药物的MIC依次为伊曲康唑、特比萘芬 < 两性霉素B < 氟康唑。同一药物在同一温度下对广西野生银星竹鼠PM寄生株与PM临床分离株的MIC无明显差异；伊曲康唑、两性霉素B、特比萘芬对同一菌株在菌丝相和酵母相下的MIC存在差异。结论 PM对伏立康唑的敏感性最高；来自于广西野生银星竹鼠的PM寄生株与临床人PM分离株对伏立康唑、伊曲康唑、特比萘芬、两性霉素B及氟康唑的MIC类似；菌相的改变可影响PM对伊曲康唑、两性霉素B、特比萘芬的敏感性。

In vitro susceptibility testing of Penicillium marneffei against several antifungal agents

Objective To test the susceptibility of Penicilliosis marneffei （PM） isolates from Guangxi bamboo rats and patients to voriconazole and several commonly used antifungal agents. Methods According to the Clinical and Laboratory Standards Institute （CLSI） M27-A2 and M38-A document, a microdilution method was used to determine the minimum inhibitory concentration（MIC） of voriconazole, itraconazole，terbinafine, amphotericin B, and fluconazole against mycelial phase （25 ℃） and yeast phase （37 ℃） of 14 PM isolates from Guangxi Bamboo rats and 25 PM isolates from patients. The difference in MIC of the antifungals was assessed by two-sample t test between Bamboo rat PM isolates and clinical PM isolates, and by paired t test between the mycelial and yeast phase of PM isolates. Results The MIC ranges of voriconazole, itraconazole, terbinafine, amphotericin B and fluconazole were 0.0313－0.1250, 0.1250－1.0000, 0.0313－0.5000, 0.2500－4.0000, 2.0000－8.0000 mg/L, respectively for mycelial phase of Bamboo rat PM isolates, 0.0078－0.2500, 0.0313－0.5000, 0.0313－1.0000, 0.2500－2.0000, 1.0000－8.0000 mg/L, respectively for yeast phase of Bamboo rat PM isolates, 0.0313－0.2500, 0.0625－1.0000, 0.0313－1.0000, 0.2500－4.0000, 2.0000－32.0000 mg/L, respectively for mycelial phase of clinical PM isolates, 0.0039－0.2500, 0.0313－0.5000, 0.0313－2.0000, 0.1250－2.0000, 2.0000－16.0000 mg/L, respectively for yeast phase of clinical PM isolates. None of the PM isolates was resistant to any of the antifungals. The MIC of voriconazole was found to be the lowest for PM isolates from both Bamboo rats and patients at the same temperature （37 ℃ or 25 ℃）, followed by itraconazole, terbinafine, amphotericin B and fluconazole. Statistical difference was found in the MIC values of itraconazole, terbinafine, amphotericin B between the yeast and mycelial phase of the same PM isolate, but not found in antifungal MIC values between Bamboo rat isolates and clinical isolates at the same phase. Conclusions Of the tested drugs, voriconazole shows the strongest antifungal potency. The PM isolates from Guangxi Bamboo rats are similar to clinical PM isolates in the sensitivity to voriconazole, itraconazole, terbinafine, amphotericin B and fluconazole. The phase of PM isolates may affect their susceptibility to itraconazole, amphotericin B and terbinafine.