临床药师参与1例氟康唑致食管癌术后肝性脑病的药学监护

目的:通过参与1例食管癌术后吻合口瘘合并混合感染重症患者使用氟康唑后出现肝性脑病的临床实践过程,探讨临床药师参与药品不良反应处理和开展药学监护的方法。方法:对患者病史、用药史及当前用药进行全面系统回顾,分析肝损伤与药物间的关系并评估用药方案,认为患者肝性脑病系氟康唑不良反应所致,协助医师制订抗感染(亚胺培南/西司他丁钠+替考拉宁)、降血氨(门冬氨酸鸟氨酸、异甘草酸镁)、保肝(还原性谷胱甘肽+多烯磷脂酰胆碱)等诊疗方案。结果:通过实施药学监护发现药源性肝性脑病,及时停用氟康唑并对症治疗,7 d后患者肝性脑病症状改善,肝功能恢复至正常。结论:临床药师应结合患者实际情况提供药学监护,及时发现不良反应,为保证合理有效用药起到积极的作用。     

肺隐球菌病3例报告并文献复习

目的 提高对肺隐球菌病的诊断和治疗水平.方法 对3例肺隐球菌病患者的临床资料进行分析,并进行文献复习.结果 3例患者均行经皮肺穿刺活检,组织病理学确诊.1、2例为轻症,第3例为重症.痰培养和支气管镜检查均阴性,血清隐球菌荚膜乳胶凝集实验均阳性,第3例脑脊液压力升高,乳胶凝集实验阳性.1、2例应用氟康唑治疗,第3例应用两性霉素B治疗,均临床治愈.结论 肺隐球菌病临床误诊率高.采用血清隐球菌荚膜乳胶凝集实验和经皮肺穿刺活检相结合的方法,可明显提高诊断率.对于免疫功能正常和轻症患者,首选氟康唑,对于免疫受损和重症患者,首选两性霉素B.     

院内真菌感染及其药物的敏感性分析

目的 :了解院内真菌感染及其药物敏感状态与疗效。方法 :对院内真菌感染危险因素、诊断及抗真菌药物敏感性进行研究。结果 :院内真菌感染 13 9例 ,占同期院内感染的 2 8 4 3 % ;感染主要部位为肺、消化道及泌尿道 ;培养出真菌 14 8株 ,白色念珠菌及热带念珠菌分别为 5 9 4 6%及 2 0 95 % ;抗真菌药物敏感性分别为AMB 5 3 90 %、 5 -FC 5 1 0 6%、KCZ 5 2 4 8%、NYS 2 8 3 7%及FCZ 61 70 % ;氟康唑治疗有效率 81 2 5 %。结论 :肺部念珠菌病最常见 ,严重基础病及长期用抗生素者发病率较高 ,治疗原发病、合理用抗生素、减少侵入性操作等有利于预防院内真菌感染 ,氟康唑治疗有效。     

氟康唑胶囊的人体药动学及其生物等效性

目的对18名健康志愿者单剂量口服两种氟康唑胶囊后的血药浓度经时过程以及两者的生物等效性进行评价。方法采用LC／MS法测定人血浆中氟康唑浓度，18名健康受试者随机分组、自身交叉口服单剂量600mg氟康唑受试制剂和参比制剂进行生物等效性评价。结果采用3P97计算两制剂的主要药动学参数：Cmax分别为（9315±1527）和（8928±1583）μg／L．Tmax分别为（1．9±0.7）和（2．0±0．7）h，t1／2分别为（32．4±6．1）和（32．6±6．4）h，用梯形法计算，AUC0-1、分别为（358749±75003）和（345997±78438）μg·h／L，AUC0-∞分别为（415346±101655）和（401636±100638）μg·h／L。结论两种氟康唑胶囊具有生物等效性。     

Kontroversen bei der Standardisierung der Empfindlichkeits-prüfung von Hefen gegen Azol-Antimyotika

Zusammenfassung. Die unterschiedlichen physikalisch-chemischen Eigenschaften der therapeutisch ein-gesetzten Azol-Antimykotika erfordern ein Testverfahren, welches diesen gerecht wird. Fluconazol kann innerhalb der Gruppe der Azol-Antimykotika aufgrund seiner Hydrophilie als unproblematische Testsubstanz angesehen werden. Die extreme Hydrophobizität des Itraconazols läßt eine Übertragung der Testbedingungen für Fluconazol auf die Itraconazoltestung nicht zu. Die aktuellen Empfehlungen des NCCLS werden dieser Problematik nicht gerecht. Deshalb ist es notwendig, einen einheitlichen Standard für die In-vitro-Testung der Gruppe der Azol-Antimykotika festzulegen.
Summary. Due to the different physical-chemical conditions of the therapeutical azoles it is necessary to choose an adequate testing procedure. In the group of azoles caused by its hydrophilia fluconazole susceptibility testing can be handled easily. However it is not possible to take the same test conditions for itraconazole as for fluconazole due to the extreme high hydrophobicity of itraconazole. The current recommendations of NCCLS should be considering these problems. Therefore it is necessary to standardize susceptibility testing for all azoles possible.     

Influence of voriconazole and fluconazole on Candida albicans in long-time continuous flow culture

We investigated the influence of voriconazole and fluconazole in a long term trial of continuous flow culture (cfc) up to 9 days. The effects of these azoles were different in dependence on the growth circumstances. Under anaerobic conditions a fungicidal effect of voriconazole was detectable, defined by an inhibition of 99.9%. This also applied to fluconazole for the majority of tested strains of C. albicans. Under aerobic conditions with an otherwise similar situation we found only a fungistatic reaction (inhibition of 90%). Fluorescence microscopy comparing fungal morphology in biofilms on glass surfaces in the cfc revealed a differentiation into blastospores, germ tubes, pseudomycelia and mycelia in the control trial after a cultivation of 8 days. Under anaerobic conditions with azoles only some single cells could be found, sometimes in cell detritus. The adhesion was clearly reduced. Under aerobic conditions more blastospores but no differentiated mycelia were to be seen.     

Early empiric antifungal therapy of infections in neutropenic patients comparing fluconazole with amphotericin B/flucytosine

We compared the efficacy and tolerability of fluconazole (FCA) with amphotericin B/flucytosine (ABF) in neutropenic patients with haematological malignancies. Antifungal therapy started on day 4 when fever was unresponsive to antibiotics or on day 1 together with the antibiotics, if there was evidence of mycosis. If patients did not respond to FCA after 7 days they switched to ABF. 98 patients, 51 FCA and 47 ABF were included in the study. Response to fever was achieved in 28/51 FCA patients and in another 16 after switching to ABF. So in overall 44/51 (86.2%) of the FCA and 37/47 (78.8%) of the ABF group defervescence was observed. 46 patients (21 FCA, 25 ABF) developed radiological signs of pneumonia. Resolution of infiltrates was achieved in 5/21 FCA and 20/25 ABF patients, and another 10 of 15 initially not responding patients showed regression when switched to ABF, 5 of these had highly suspected aspergillosis. Adverse events occurred in 19.6% of FCA and 97.9% of ABF patients. In conclusion fluconazole and amphotericin B/flucytosine seem to be equally effective. In view of its lower toxicity fluconazole may be preferred as first line empiric antifungal agent, but in case of nonresponse, pneumonia or aspergillosis it may be replaced by amphotericin B combined with flucytosine.