氟康唑食管给药与静脉给药的药代动力学对比研究

目的:进行氟康唑食管给药与静脉给药的药代动力学研究。方法:采用HPLC法测定14名受试者静脉及食管给予氟康唑后经时血浓度,比较药代动力学参数及药物生物利用度变化。结果:两种给药途径,氟康唑主要药代动力学参数Cmax为(13.31±1.38)和(10.93±0.73)μg/ml,Tmax为(1.04±0.19)和(1.74±0.73)h,T1/2为(40.77±7.13)和(40.05±4.90)h,AUC为(271.09±30.48)和(261.93±32.60)μg/ml·h。食管给药生物利用度为(95.93±6.49)%,两种给药途径的生物利用度无统计学差异(P>0.05)。结论:食管给药是一种安全有效的给药方法。     

国产氟康唑对小鼠隐球菌病的疗效

以５×１０３ｃｆｕ／鼠的新型隐球菌给小鼠脑室感染（ｉｃ）１ｈ后，分别口服氟康唑（Ｆｌｕ）５和１０ｍｇ／（ｋｇ·ｄ）或酮康唑（Ｋｅｔ）５０和１００ｍｇ／（ｋｇ·ｄ），ｂｉｄ×９ｄ。对ｉｃ小鼠连续观察４０天的存活率和平均存活时间，Ｆｕｌ分别为５０％～７０％和８～１５天，Ｋｅｔ是３０％～４０％和５～９天。由小鼠侧尾静脉注射１０６ｃｆｕ／鼠新型隐球菌３天后产生的全身感染，分别给小鼠口服Ｆｌｕ２．５～１０ｍｇ／（ｋｇ·ｄ）或Ｋｅｔ２５～１００ｍｇ／（ｋｇ·ｄ），ｂｉｄ×９ｄ。感染２４、２８和３２天的ＰＤ５０Ｆｌｕ是２．７、３．５和６．７ｍｇ／ｋｇ，Ｋｅｔ为２８．４、７０．４和８３ｍｇ／ｋｇ；Ｆｌｕ和Ｋｅｔ的平均存活时间分别是２３～３４天和２０～３１天。在上述两种实验模型中分离脑和肺做细菌培养，Ｆｌｕ均与对照和５０ｍｇ／（ｋｇ·ｄ）的Ｋｅｔ比较，对ｉｃ１０天及静脉注射感染１３天的小鼠，口服５和１０ｍｇ／（ｋｇ·ｄ）或２．５～１０ｍｇ／（ｋｇ·ｄ）Ｆｌｕ均显著抑制新型隐球菌生长。     

氟康唑治疗念珠菌性龟头包皮炎53例疗效观察

目的　探讨氟康唑对念珠菌性龟头包皮炎的临床疗效。方法　将 98例患者随机分为两组 ,治疗组 ( 5 3例 )口服氟康唑 15 0mg ,qd× 5d ,用药期间停用其它的口服药及外用真菌药 ;对照组 ( 4 5例 )用霉克霜外搽患处 ,bid ,连用 2W ,用药期间停用口服药。结果　治疗组痊愈率为 90 .5 7% ,总有效率为 98.11% ;对照组痊愈率为 2 .2 2 % ,总有效率为 66.67% ,治疗组均显著高于对照组 (P均 <0 .0 1)。结论　氟康唑治疗念珠菌性龟头包皮炎疗效满意     

白色念珠菌对五种抗真菌药物体外敏感性研究

目的了解白色念珠菌对常用抗真菌药物的敏感性情况,为临床正确选择抗真菌药物和有效控制该菌引起的感染提供依据。方法采用美国国家临床实验标准委员会(NCCLS)推荐的微量肉汤稀释法,测定从临床标本中分离的102株白色念珠菌对五种抗真菌药的最低抑菌浓度(MIC)。结果酮康唑、氟胞嘧啶和伊曲康唑对102株白色念珠菌MIC较低,其MIC90分别为0.25μg/ml、0.5μg/ml和0.5μg/ml。两性霉素B和氟康唑MIC90分别为2μg/ml和8μg/ml。受试菌对氟胞嘧啶敏感率最高为100%,对氟康唑和伊曲康唑的敏感率分别为88.3%和75.5%。对氟康唑耐药的9株菌株也同时对伊曲康唑耐药。结论受试白色念珠菌对氟胞嘧啶敏感率最高,未发现耐药菌株;酮康唑对受试菌抗菌活性最强,对唑类药物存在耐药性,且该类药物之间存在交叉耐药。     

Effect of administration of diethylcarbamazine with and without fluconazole on experimental fungal infections in mice

Other researchers have found that diethylcarbamazine (DEC) is effective treatment for filariasis despite a lack of demonstrated in vitro antifilarial activity. The results of our previous investigations using feline and murine leukemia virus models encouraged us to investigate the use of DEC with other infections. In our current experiments, DEC treatment was associated with lower brain fungal burden in fluconazole-treated mice following intravenous injection of Aspergillus fumigatus or increasing numbers of Cryptococcus neoformans organisms, and lower brain and kidney levels of Candida albicans following intravenous injection of increasing numbers of C. albicans. Further investigation of combined DEC and fluconazole treatment of fungal infections is warranted.     

氟康唑治疗真菌性角膜溃疡的临床观察

目的 :观察氟康唑治疗真菌性角膜溃疡的疗效。方法 :采用局部或全身应用氟康唑 ,治疗真菌性角膜溃疡 42眼。结果 :治疗组 42眼 ,治愈 3 1眼 ,治愈率 73 .8% ,疗程 1 0～ 2 6d,平均 1 4d;对照组 2 3眼 ,治愈 1 0眼 ,治愈率 43 .4% ,疗程 1 4～ 1 8d,平均 2 8d。两组治愈率有显著性差异 (P<0 .0 5 )。结论 :氟康唑是目前治疗真菌性角膜溃疡疗效较好的药物。     

Acquired fluconazole resistance and genetic clustering in Diutina (Candida) catenulata from clinical samples

ObjectivesDiutina (Candida) catenulata is an ascomycetous yeast isolated from environmental sources and animals, occasionally infecting humans. The aim of this study is to shed light on the in vitro antifungal susceptibility and genetic diversity of this opportunistic yeast.MethodsForty-five D. catenulata strains isolated from various sources (including human and environmental sources) and originating from nine countries were included. Species identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and confirmed via internal transcribed spacer ribosomal DNA barcoding. In vitro antifungal susceptibility was determined for seven systemic antifungals via the gradient strip method after 48 hours of incubation at 35°C using Etest® (Biomérieux) or Liofilchem® strips. Isolates exhibiting fluconazole minimal inhibitory concentrations (MICs) of ≥8 μg/mL were investigated for mutations in the ERG11 gene. A novel microsatellite genotyping scheme consisting of four markers was developed to assess genetic diversity.ResultsMIC ranges for amphotericin B, caspofungin, micafungin, isavuconazole, and posaconazole were 0.19–1 μg/mL, 0.094–0.5 μg/mL, 0.012–0.064 μg/mL, 0.003–0.047 μg/mL, and 0.006–0.032 μg/mL, respectively. By comparison, a broad range of MICs was noted for fluconazole (0.75 to >256 μg/mL) and voriconazole (0.012–0.38 mg/L), the higher values being observed among clinical strains. The Y132F amino acid substitution, associated with azole resistance in various Candida species (C. albicans, C. tropicalis, C. parapsilosis, and C. orthopsilosis), was the main substitution identified. Although microsatellite typing showed extensive genetic diversity, most strains with high fluconazole MICs clustered together, suggesting human-to-human transmission or a common source of contamination.DiscussionThe high rate of acquired fluconazole resistance among clinical isolates of D. catenulata is of concern. In this study, we highlight a link between the genetic diversity of D. catenulata and its antifungal resistance patterns, suggesting possible clonal transmission of resistant isolates.     

氟康唑注射液临床流向调查及62例二重感染病例的抗生素用药分析

目的对氟康唑注射液临床流向进行调查以确定其用药的合理性;对二重感染病例的抗生素应用情况及其他相关因素进行分析,以减少用药的盲目性。方法采用时间段内大面积调查方法,对2003年9月至12月所用全部氟康唑注射液的临床流向进行全面调查,对确认的62例真菌二重感染病例的原发疾病、致病菌及其耐药性、抗生素使用的详细资料进行调查分析。结果639瓶氟康唑注射液流向12个科室,84例患者,其中二重感染病例62例,占患者总数的74%;62例二重感染病例多存在免疫力低下,病情严重及耐药菌株感染的特定情况,10d之内抗生素应用品种达24种,单品种累计换算限定日剂量数(DDDs)达982。抗生素用药档次高、联用多、用时长。结论控制真菌二重感染已成为氟康唑注射液临床用药的主要目的;广谱、高效抗生素的过度使用是诱导二重感染的重要原因,滥用抗生素会导致院内感染失控,二重感染增多的恶性循环。