伊曲康唑序贯疗法治疗老年MODS患者侵袭性肺部真菌感染14例

目的 观察伊曲康唑序贯疗法治疗老年多脏器功能障碍综合征（MODS）患者侵袭性肺部真菌感染的疗效。方法 回顾分析重症监护病房（ICU）中,老年MODS患者侵袭性真菌感染14例,最初应用伊曲康唑注射液7～14d,第1～2d,200mg,1次／12h,第3～14d,200mg,1次／d;然后,采用伊曲康唑胶囊或口服液序贯治疗,400mg／d剂量水平,疗程2—4周。结果 临床有效率85．7％,真菌清除率为92．9％,真菌清除平均天数为6．1d;患者28d生存率85．7％,不良反应发生率为42．9％。结论 对老年MODS合并侵袭性真菌感染患者在综合治疗的基础上,应用广谱抗真菌药物——伊曲康唑序贯疗法,是巩固疗效,防止复发值得推广的给药方式。临床应用伊曲康唑时,应注意适应证、药物不良反应及药物的相互作用。     

两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合治疗隐球菌性脑膜炎的临床回顾性研究

目的 观察两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合治疗非AIDS、非器官移植隐球菌性脑膜炎患者的疗效和安全性,探讨非AIDS、非器官移植隐球菌性脑膜炎患者诱导治疗的新方案.方法 采用回顾性病例对照研究,18例非AIDS、非器官移植隐球菌性脑膜炎患者诱导期分别接受两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合(研究组n=7)与两性霉素B、氟胞嘧啶和氟康唑联合治疗(对照组n=11).比较两组治疗方案在临床症状、体征变化、病死率、病原学转阴率、脑脊液改变等方面的差异及血常规、肝肾功能损害等不良反应发生情况.结果 治疗前研究组和对照组脑脊液新型隐球菌培养阳性分别为5例和8例(P =0.676),治疗1周后分别为5例和8例(P =0.676),治疗2周后分别为2例和4例(P =0.572),治疗3周后分别为0例和1例(P=0.611),治疗4周后,无死亡病例,两组脑脊液新型隐球菌培养均为阴性,脑脊液生化两组之间差异无统计学意义,对照组较研究组丙氨酸氨基转移酶(156.82±41.30 vs 97.00±22.02,P=0.003)、尿素氮(8.45±3.18 vs 5.54±1.28,P=0.020)升高更明显.结论 两性霉素B脂质体、氟胞嘧啶及伊曲康唑联合治疗非AIDS、非器官移植隐球菌性脑膜炎患者疗效确切,安全性较好,可以作为诱导期治疗的选择.     

Comparative efficacy of amphotericin B,clotrimazole and itraconazole againstAspergillus spp.

The susceptibilities of two isolates ofAspergillus flavus, one from a human case of recalcitrant mycotic keratitis, and an environmental isolate ofA. fumigatus, to itraconazole, clotrimazole and amphotericin B were measured. Observations of macroscopic growth and microscopic evaluations of conidia germination both indicated that the two isolates ofA. flavus were markedly more resistant to amphotericin B than to itraconazole and clotrimazole. Itraconazole was more effective than clotrimazole for all isolates. Ourin vitro susceptibility results suggest the use of itraconazole should be a primary consideration in the treatment ofAspergillus keratitis.     

Rapid quantification of itraconazole-resistant Aspergillus fumigatus in air

Solid-phase cytometry (SPC) was used to determine the total number and the number of itraconazole-resistant Aspergillus fumigatus cells in 60 air samples. Of the 570 A. fumigatus cells that were recovered, 10 (1.8%) were resistant. SPC proved more specific and rapid than culture and allowed high-troughput susceptibility testing.     

Design and synthesis of pyridine-substituted itraconazole analogues with improved antifungal activities, water solubility and bioavailability

To improve antifungal activities, water solubility and bioavailability, a series of novel analogues of itraconazole-containing pyridine rings were designed and synthesized. Their antifungal activities were evaluated in vitro against six clinically important fungi by measuring the minimal inhibitory concentrations (MICs). Most of the compounds showed more potent antifungal activities than that of itraconazole. In particular, the analogues 30d, 30c, 31c, and 36d exhibited much higher solubility and bioavailability than that of itraconazole. The bioavailability of 36d (42.2%) was five times higher than that of itraconazole (8%) and was negative for genetic toxicology in the Ames test.     

Stereoselective determination of the epimer mixtures of itraconazole in human blood plasma using HPLC and fluorescence detection

Itraconazole is an antifungal drug widely used in a variety of fungal infections, which have become a significant public-health problem in recent decades. Itraconazole is a chiral drug consisting of two diastereoisomeric racemates, i.e., four stereoisomers. Data in the literature suggests that stereochemistry may play a significant role in the action and disposition of the drug and therefore stereoselective analytical methods for the determination of the drug in biological fluids are needed for the elucidation of that role. We report a stereoselective HPLC method that incorporates solvent extraction, the use of an internal standard, two chiral stationary phases in series, and fluorescence detection. The procedure is enantioselective and partially diastereoselective and provides the concentrations in blood plasma of the two epimer mixtures 2R,4S,2'R/2R,4S2'S and 2S,4R,2'R/2S,4R,2'S, respectively, each of which is a combination of the two epimers that differ in the configuration at the sec-butyl group. The analytical method has suitable sensitivity, recovery, precision, and accuracy. Analysis of the plasma of a human subject six hours after the oral administration of a single 200-mg dose of itraconazole showed a 3.4-fold difference between the concentrations of the epimer mixtures. The method has certain advantages over the published alternative procedure that uses LC-MS.     

泊沙康唑在预防恶性血液病患者侵袭性真菌病中的应用研究

摘要 目的：研究泊沙康唑在预防恶性血液病患者侵袭性真菌病中的应用效果。方法：选取我院2018年1月~2019年9月收治的50例恶性血液病患者,按照随机数余数分组法分为采取泊沙康唑预防的泊沙康唑组以及采取伊曲康唑预防的伊曲康唑组各25例,对两组预防效果进行对比。结果：泊沙康唑组预防治疗成功率为84.00 % (21/25),显著高于伊曲康唑组的68.00 % ( 17/25),侵袭性真菌病发生率为4.00 % (1/25),显著低于伊曲康唑组的16.00 % (4/25)（P＜0.05）;给药前两组炎性细胞因子差异无统计学意义（P＞0.05）,给药结束后均较本组给药前降低（P＜0.05）,组间比较泊沙康唑组均低于伊曲康唑组（P＜0.05）;泊沙康唑组治疗期间不良反应发生率为8.00 % (2/25),伊曲康唑组治疗期间不良反应发生率为20.00 % (5/25),两组不良反应发生率对比无统计学意义（P＞0.05）。结论：在预防恶性血液病患者侵袭性真菌病中泊沙康唑效果更佳且安全性高,可作为优选用药方案推广使用。     

Rapid method for the analysis of itraconazole and hydroxyitraconazole in serum by high-performance liquid chromatography

An assay for the determination of itraconazole and its active metabolite hydroxyitraconazole in serum has been developed, using ketoconazole as internal standard. The procedure involved a one-step liquid-liquid extraction of the drug, its metabolite and the internal standard, followed by their separation by reversed-phase HPLC. In this paper the validation of this method is described.     

In vitro inhibitory activity of sertraline against clinical isolates of Sporothrix schenckii

BackgroundSertraline (SRT) is an antidepressant that has proven its activity in vitro against Cryptococcus, Coccidioides, Trichosporon and other fungi. Disseminated sporotrichosis, although rare, has a high mortality and its treatment is difficult and prolonged, often relying in combining two or more antifungals.AimsIn our study we evaluate the antifungal activity of SRT, alone and in combination with itraconazole (ITC), voriconazole (VRC) and amphotericin B (AMB), against 15 clinical isolates of Sporothrix schenckii.MethodsWe used the broth microdilution method as described by the CLSI to test the susceptibility to antifungals, and the checkerboard microdilution method to evaluate drug interactions.ResultsThe minimum inhibitory concentration (MIC) with SRT was in the range of 4–8 μg/ml, while for AMB, VRC and ITC were 0.5–4 μg/ml, 0.5–8 μg/ml and 0.125–2 μg/ml, respectively. In addition, SRT showed synergy with ITC in one strain, mainly additivity with VRC, and indifference with AMB in others.ConclusionsThe MIC values with SRT for the isolates studied show the potential role of this drug as an adjuvant in the treatment of sporotrichosis, especially in disseminated or complicated cases.     

Itraconazole loaded nano-structured lipid carrier for topical ocular delivery: Optimization and evaluation

Background & ObjectivesLow penetration efficiency and retention time are the main therapeutic concerns that make it difficult for most of the drugs to be delivered to the intraocular tissues. These challenging issues are often related to those drugs, which have low or poor solubility and low permeability. The goal of this study was designed to develop nanostructured lipid carriers (NLCs) loaded with itraconazole (ITZ) with the objective of enhancing topical ocular permeation and thereby improving clinical efficacy.Materials and MethodsITZ-loaded NLCs were fabricated by a high-speed homogenization technique using surfactant (Poloxamer 407), and lipids (stearic acid and oleic acid). Optimization of formulations was performed by 3 level factorial design and the selected formulation (F6) was evaluated by differential scanning calorimetry and transmission electron microscopy. Antifungal activity was assessed by measuring the zone of inhibition and irritation potential using the HET-CAM test.ResultsThe independent variables (lipid ratio-X₁ and percentage of emulsifier-X₂) have a positive impact on percentage entrapment efficiency (Y₂) and percentage release (Y₃) but have a negative impact on particle size (Y₁). Based on the better entrapment efficiency (94.65%), optimum particle size (150.67 nm), and percentage cumulative drug release (68.67%), batch F6 was selected for further evaluation. Electron microscopic images revealed that the prepared particles are spherical and have nano size. Antifungal studies demonstrated enhancement in the zone of inhibition by formulation F6 as compared to a commercial eye drop. The non-irritancy of optimized formulation (F6) was confirmed with a zero score.Interpretation & ConclusionIn summary, the optimized NLCs seem to be a potent carrier for the effective delivery of itraconazole in ocular therapy.