氟康唑治疗44例隐球菌脑膜炎效果研究

目的对氟康唑治疗44例隐球菌脑膜炎效果的效果进行研究。方法 44例都给予氟康唑400mg静脉滴注,1次/d;其中5例53d后改为200mg口服1次/d;另10例120d后改为200mg口服1次/d,24例采用氟康挫200mg静脉滴注,1次/d。结果 44例使用了氟康挫治疗的隐球菌脑膜炎患者中,有除有2例死亡外,其余的42例患者的治疗效果都十分良好,且没有出现严重的不良反应。结论对隐球菌脑膜炎的治疗,首选系统性抗真菌的金标准就是采用两性霉素B在,但由于肝、肾毒性大,很多患者不能耐受该药物的治疗;然而使用氟康唑可以作为补救治疗的首选方案,早期足量长疗程应用氟康唑可以用于治疗绝大多数新型隐球菌脑膜炎患者。     

抗真菌药的近况与开发

９０年代在抗真菌药上有很大进展,主要是三唑类的伊曲康唑和氟康唑。实验证明,伊曲康唑治疗曲霉感染有效;氟康唑治疗隐球菌性脑膜炎有效,最新推出两性霉素Ｂ脂质体,这种剂型能明显地减轻两性霉素Ｂ对肾脏的毒性,并有极佳的疗效。     

新的唑类抗真菌药BMS-207147体内和体外的抗新型隐球菌活性

BMS 2 0 71 4 7是一个新的口服唑类抗真菌药物。本研究中 ,我们采用微量稀释法测定了BMS 2 0 71 4 7对于 2 6株临床分离的新型隐球菌体外敏感性 (MICs) ,且通过用BMS 2 0 71 4 7治疗鼠肺隐球菌病了解体内抗隐球菌疗效 ,并与氟康唑进行了比较。对于 2 6株新型隐球菌的MIC90 ,BMS 2 0 71 4 7为 0 0 62 5mg/L ,氟康唑是它的 32倍 ;伊曲康唑是它的 4倍 ;伏立康唑 (voriconazole)是它的 2倍。而且对于氟康唑耐药的新型隐球菌的MIC ,伊曲康唑和伏立康唑是BMS 2 0 71 4 7的 4倍。在肺隐球菌病的鼠模型实验中 ,BMS 2 0 71 4 7不仅能显著地降低由氟康唑敏感菌株感染的肺内菌数和脑内菌数 (CFU/ml) ,(与对照组比较P <0 0 5) ;而且能显著地降低氟康唑耐药新型隐球菌感染的肺内菌数和脑内菌数 (CFU/ml) ,与氟康唑治疗组相比较P <0 0 5。结论 :BMS 2 0 71 4 7具有高效的体内、体外抗新型隐球菌活性     

伊曲康唑与氟康唑在重症监护室早期经验性治疗真菌感染的疗效比较

目的比较伊曲康唑和氟康唑在重症监护室早期经验性治疗中的有效性和安全性。方法采取随机、对照、开放的临床试验，入选的40例患者具有真菌感染的高危因素，均出现不明原因发热，广谱抗生素治疗3～7 d无效。将入选患者随机分配为伊曲康唑治疗组和氟康唑治疗组各20例。伊曲康唑治疗组给予伊曲康唑注射液200 mg，q12 h，先治疗2 d，随后给予200 mg，qd，共5 d，再改用伊曲康唑口服液口服，每次200 mg，bid，治疗14 d；氟康唑治疗组给予氟康唑注射液400 mg静脉滴注，qd，共治疗21 d。观察患者体温变化、真菌感染情况、药物相关的不良反应和疗效。结果伊曲康唑组总有效率65.0%，不良反应率30.0%；氟康唑组总有效率50.0%，不良反应率5.0%，但两组总有效率和不良反应发生率均差异无显著性（均P＞0.05）。治疗过程中，氟康唑组出现2例深部真菌感染。结论伊曲康唑和氟康唑均可作为现阶段重症监护室早期经验性治疗的一线药物，但伊曲康唑疗效更佳。     

SCH-56592对新型隐球菌体内外抗真菌活性

目的评价新的唑类抗真菌药物SCH-56592体内外抗临床分离的新型隐球菌活性.方法依照美国国家临床试验标准化委员会推荐的M27-A方案的微量稀释法测定26株新型隐球菌对SCH-56592及氟康唑、伊曲康唑和两性霉素B的MICs.比较SCH-56592与氟康唑治疗免疫功能抑制的鼠肺隐球菌病的疗效.结果SCH-56592对于临床分离的26株新型隐球菌的体外抗菌活性是氟康唑的16～64倍,对氟康唑耐药的新型隐球菌的MIC(0.05μg@mL-1)是伊曲康唑MIC(2μg@mL-1)的1/40倍.SCH-56592不仅明显降低氟康唑敏感新型隐球菌株感染小鼠的肺内菌数(P＜0.05)[SCH-56592组为(2.90±1.90)×107CFU@mL-1,对照组为(46.60±29.58)×107CFU@mL-1];而且明显降低氟康唑耐药的新型隐球菌株感染的小鼠肺内菌数[SCH-56592组为(5.30±2.36)×107CFU-mL-1,对照组为(197.70±10.37)×107CFU@mL-1,氟康唑治疗组为(190.60±97.63)×107CFU@mL-1,与后2组比较,均为P＜0.05].肺隐球菌感染的小鼠经SCH-56592治疗后生存时间延长,生存率提高.结论SCH-56592具有良好的体内、体外抗临床分离的新型隐球菌活性;对于氟康唑耐药的新型球菌具有极好的抗真菌活性.     

伊曲康唑治疗中枢神经系统真菌感染的临床开放研究

目的:观察伊曲康唑注射液和口服液序贯治疗中枢神经系统真菌感染的疗效,以及与两性霉素B和(或)氟胞嘧啶联合应用时的安全性。方法:采用开放性临床研究,自2004年6月-2005年9月间共收治17例中枢神经系统真菌感染,均采用伊曲康唑单独或联合两性霉素B和(或)氟胞嘧啶治疗,伊曲康唑注射液治疗至少1 wk以上。伊曲康唑注射液静脉滴注d 1～2为200 mg,q 12 h,d 3～14为200 mg·d-1;继之伊曲康唑口服液200 mg,q 12 h序贯治疗,两性霉素B 20～30 mg·d-1缓慢静脉滴注和(或)氟胞嘧啶6 g·d-1,分4次口服。结果:确诊病例14例,临床诊断病例3例,病原菌包括隐球菌、曲霉菌和小型无绿藻。2例治疗2 d死亡,未纳入疗效评估,临床总有效率为73％(11／15)。其中2例脑曲霉病、1例无绿藻脑膜炎、8例隐球菌脑膜炎(隐脑)均获痊愈;3例隐脑进步,1例侵袭性脑曲霉病无效死亡。治疗过程中,伊曲康唑注射液的不良反应主要为轻度肝功能异常,口服液治疗中部分病人有消化道症状,包括恶心、食欲下降,发生在服药2 mo以后。结论:伊曲康唑注射液和口服液单独或联合其他抗真菌药物治疗中枢神经系统真菌感染具有较好的疗效和安全性。     

伏立康唑静脉滴注致黄视

1例77岁男性患者,因慢性阻塞性肺疾病伴肺部感染给予亚胺培南-西司他丁钠0.5 g入0.9%氯化钠注射液100 ml,3次/d静脉滴注;利奈唑胺0.6 g,2次/d静脉滴注;氨溴索0.045 g入0.9%氯化钠注射液50 ml,2次/d静脉滴注。因曲霉菌感染于第4天加用伏立康唑0.2 g,2次/d静脉滴注。第3次静脉滴注伏立康唑后,患者出现视物黄色,遂将伏立康唑改为0.2g,2次/d口服,其余药物继续应用。口服用药第2天,患者黄视症状明显减轻;第6天,症状完全消失。继续口服伏立康唑9d,其间患者未再出现黄视。     

3种抗真菌药治疗甲真菌病药物经济学分析

目的对伊曲康唑、特比萘芬、氟康唑3种不同抗真菌药物治疗120例甲真菌病患者的成本效果分析。方法选择120例病例,随机分为3组,分别给予伊曲康唑、特比萘芬、氟康唑治疗,观察各组疗效并运用药物经济学方法进行分析。结果3种药物均有较好的抗真菌疗效,特比萘芬疗效优于伊曲康唑及氟康唑,伊曲康唑疗效优于氟康唑。平均成本-效果比分别为8.9,8.0,11.7。结论药物经济学分析结果为特比萘芬治疗甲真菌病最优。     

常用抗真菌药物治疗新型隐球菌性脑膜炎的疗效对比

新型隐球菌性脑膜炎是隐球菌属中某些变异菌侵犯中枢神经系统的一种深部真菌感染。传统治疗药物有氟胞嘧啶、两性霉素B、氟康唑及伊曲康唑,近年来。为了降低两性霉素B的毒性并提高其疗效,研制出两性霉素B脂质体。对上述抗真菌药物作用机制、药动学、临床疗效及不良反应的对比分析,可为临床新型隐球菌性脑膜炎更合理、更安全、更有效的治疗提供参考。     

氟康唑致精神障碍

1例79岁股癣患者,因股骨头置换术后预防真菌感染给予氟康唑200 mg/d静脉滴注.输液完毕后3 h,患者出现面色潮红、多语、失眠,呈轻度兴奋状态.次日症状好转,再次输入氟康唑,上述症状复现,并出现定向障碍、情绪亢奋、思维奔逸、幻视及被害妄想.停用氟康唑,改为伊曲康唑0.2 g,1次/d口服,2 d后症状消失.     

临床药师参与治疗1例马尔尼菲青霉菌肺部感染

1例63岁中老年男性因“咳嗽、发热伴淋巴结肿大1月余”入院,根据淋巴结穿刺的病理结果确诊为马尔尼菲青霉菌肺部感染。患者病情严重,感染累及心脏,全身炎症反应强烈。确诊后立即给予伊曲康唑注射液抗真菌治疗,但在治疗的第19天,医生将伊曲康唑注射液改为伊曲康唑胶囊序贯治疗,临床药师考虑到患者此时的病情尚不稳定且伊曲康唑口服胶囊的生物利用度低,其血药浓度达不到有效抗菌浓度,建议继续使用伊曲康唑注射液控制病情,待患者病情稳定后可考虑给予生物利用度较高的伊曲康唑口服溶液序贯治疗。临床医生采纳临床药师的意见,继续给予伊曲康唑注射液治疗,1周后患者病情相对稳定,予以出院。3周后患者门诊随访,病情进一步好转,且无药物不良反应发生。     

Pharmacoeconomic analysis of oral antifungal therapies used to treat dermatophyte onychomycosis of the toenails. A US analysis

Until a few years ago, griseofulvin and ketoconazole were the only 2 oral agents available for the treatment of dermatophyte onychomycosis of the toenails. With the availability of the newer antifungal agents, such as itraconazole, terbinafine and fluconazole, the armamentarium of drugs available to treat onychomycosis has expanded. The objective of this study was to determine the relative cost effectiveness of the most commonly used oral antifungal agents in the US for the treatment of dermatophyte onychomycosis of the toenails from the perspective of a third-party payer. The time horizon was 3 years. A 5-step approach was used in this pharmacoeconomic analysis. First, the purpose of the study, the comparator drugs and their dosage regimens were defined. In step II, the medical practice and resource-consumption patterns associated with the treatment of onychomycosis were identified. In step III, a meta-analysis was performed on all studies meeting prespecified criteria, and the mycological cure rates of the comparator drugs were determined. In step IV, the treatment algorithm for the management of onychomycosis was constructed for each drug. The cost-of-regimen analysis for each comparator incorporated the drug acquisition cost, medical-management cost and cost of managing adverse drug reactions. The expected cost per patient, number of symptom-free days (SFDs), cost per SFD and the relative cost effectiveness for the comparator drugs were calculated. In step V, a sensitivity analysis was performed. The drug comparators for this study were griseofulvin, itraconazole (continuous and pulse), terbinafine and fluconazole. The mycological cure rates [mean +/- standard error (SE)] from the meta-analysis were griseofulvin 24.5 +/- 6.7%, itraconazole (continuous) 66.4 +/- 6.1%, itraconazole (pulse) 76 +/- 9.3%, terbinafine 74 +/- 7% and fluconazole 59%. The cost per mycological cure was griseofulvin $US8089, itraconazole (continuous) $US1877, itraconazole (pulse) $US991, terbinafine $US1125 and fluconazole $US1506. The corresponding cost per SFD was griseofulvin $US7.05, itraconazole (continuous) $US2.18, itraconazole (pulse) $US1.26, terbinafine $US1.28 and fluconazole $US2.12. The resulting ratios of cost per SFD relative to itraconazole (pulse) [1.00] were terbinafine 1.02, itraconazole (continuous) 1:73, fluconazole 1.69 and griseofulvin 5.62. In conclusion, in this analysis, itraconazole (pulse) and terbinafine were the most cost-effective therapies for dermatophyte onychomycosis of the toenails, both being substantially more cost effective than griseofulvin.     

Pharmacokinetics of antifungal agents in onychomycoses

Onychomycosis is caused by infection by fungi, mainly dermatophytes and nondermatophyte yeasts or moulds; it affects the fingernails and, more frequently, the toenails. Dermatophytes are responsible for about 90 to 95% of fungal infections. Trichophyton rubrum is the most common dermatophyte; Candida albicans is the major nondermatophyte yeast. Although topical therapy of onchomycosis does not lead to systemic adverse effects or interactions with concomitantly taken drugs, it does not provide high cure rates and requires complete compliance from the patient. At present there are 3 oral antifungal medications that are generally used for the short term treatment of onychomycosis: itraconazole, terbinafine and fluconazole. The persistence of these active drugs in nails allows weekly administration, reduced treatment or a pulse regimen. Good clinical and mycological efficacies are obtained with itraconazole 100 to 200 mg daily, terbinafine 250mg daily for 3 months, or fluconazole 150 mg weekly for at least 6 months. Itraconazole is a synthetic triazole with a broad spectrum of action. It is well absorbed when administered orally and can be detected in nails 1 to 2 weeks after the start of therapy. The nail : plasma ratio stabilises at around 1 by week 18 of treatment. Itraconazole is still detectable in nails 27 weeks after stopping administration. Nail concentrations are higher than the minimum inhibitory concentration (MIC) for most dermatophytes and Candida species from the first month of treatment. The elimination half-life of itraconazole from nails is long, ranging from 32 to 147 days. Terbinafine is a synthetic allylamine that is effective against dermatophytes. Terbinafine is well absorbed from the gastrointestinal tract, and the time to reach effective concentrations in nail is 1 to 2 weeks. The half-life is from 24 to 156 days, explaining the observed persistence of terbinafine in nails for longer than 252 days. Fluconazole is a bis-triazole broad spectrum antifungal with high oral bioavailability. The uptake of fluconazole by nail increases with the length of treatment, and nail : plasma ratios are generally 1.5 to 2 at steady state. Fluconazole concentrations exceed the MIC for Candida species soon after the start of treatment. Fluconazole concentrations fall slowly after the drug is stopped, with a half-life of 50 to 87 days, and fluconazole is still detectable in nails 5 months after the end of treatment. All these drugs are potent inhibitors of cytochrome P450 (CYP) enzymes and may increase the plasma concentrations of concomitantly used drugs. Itraconazole inhibits CYP3A4. Fluconazole inhibits CYP3A4, but to a lesser degree than itraconazole, CYP2C9 and CYP2C19. Terbinafine inhibits CYP2D6.     

临床药师在1例病毒性脑炎伴癫痫发作患者药物治疗中的作用

目的:探讨临床药师在重症监护室重症患者药物治疗实践中发挥的作用。方法:通过临床药师对1例病毒性脑炎伴癫痫发作的患者实施药学监护,关注患者用药方案中抗病毒药物及抗菌药物的选择、抗癫痫药物相互作用及药品不良反应等几个方面,协助医师为患者制订个体化的治疗方案。结果:20 d后,患者一般状态较前明显好转,各项生命体征平稳,转入康复科继续治疗,1月后康复出院。结论:临床药师对病毒性脑炎伴癫痫发作的患者实施药学监护可以提高患者用药的安全性、有效性,体现临床药师价值。     

药师参与1例开颅手术后颅内及肺部感染患者的药物治疗分析

1例45岁男性患者,以“左侧桥小脑角区（CPA）占位”入院,行左CPA肿瘤切除术后持续发热。痰培养为耐甲氧西林金葡菌感染,根据药敏试验给予替考拉宁治疗后仍有发热,症状未缓解,脑脊液检查示颅内感染。临床药师依据病原学检查、药代动力学特点以及结合相关文献资料对抗感染治疗方案提出了合理化建议,建议临床医生将替考拉宁替换为万古霉素,并在病情控制不佳的情况下调整万古霉素给药剂量,患者治疗6日后,感染得到控制。     

1例白血病合并侵袭性肺部真菌感染患者的药学监护

1例48岁男性患者,因确诊急性淋巴细胞白血病2个月入院化疗.入院后行Hyper-CVAD-A方案化疗后出现粒细胞缺乏,双下肺感染加重,结合患者既往用药史及相关抗真菌指南,临床药师建议联合采用两性霉素B和米卡芬净进行抗真菌治疗,并给予升白、补钾和护肝等支持治疗.同时,针对化疗方案和抗真菌药物可能导致的血液、胃肠道、肝肾功能等不良反应提供全面的药学监护.10d后,患者复查双肺炎症状明显减轻,出院.     

临床药师参与1例肾移植术后肺结核患者抗结核治疗的药学实践

摘 要临床药师基于循证证据,结合患者病情,与医生合作,积极参与1例肾移植术后肺结核患者的抗结核治疗,给患者提供药学服务。根据现有指南、临床研究,考虑用药经济性的基础上,临床药师对患者治疗药物的选择、药品相互作用及不良反应等方面进行合理性分析,促进合理用药。     

临床药师对1例心房颤动致脑栓塞患者的用药干预与监护

摘 要 目的： 通过神经内科临床药师参与药物治疗实践,提高心房颤动致脑栓塞患者药物治疗的有效性、安全性,以及患者的用药依从性。方法: 临床药师全程积极参与1例心源性脑梗死患者的治疗,在药物的选用、药物相互作用、不良反应的监护、相关指标的监测以及患者出院用药宣教等方面提供药学服务。结果: 临床医师与临床药师紧密合作,选用合理药物,避免药物间相互作用;患者服药依从性提高,好转后出院。结论: 临床药师积极参与心源性脑梗死患者的药物治疗,可提高药物治疗的有效性和安全性。     

临床药师参与1例慢性肾功能不全伴尿路感染的治疗实践

目的通过临床药师参与1例慢性肾功能不全伴尿路感染的治疗实践,探讨药师在合理用药中发挥的作用。方法临床药师积极参与了该患者的抗感染,控制高血压,纠正贫血,抗凝的治疗实践,针对患者的治疗方案,药品的选择、剂量、相互作用、不良反应、注意事项等提出了一些合理化的建议,同时对患者实施了药学监护,健康教育和用药教育。结果临床药师参与治疗实践,提高了临床治疗效果。患者住院用药期间无相关不良反应发生,出院时尿路感染已经控制,血压平稳,无电解质紊乱,病情控制尚可。结论临床药师参与临床药物治疗,为病人提供个体化药学服务,可使用药更合理、有效和经济;临床药师只有参与临床实践与临床医师密切配合,才能有助于更好地开展临床药学服务工作,更好地为病人服务。     

Involvement of phenobarbital and SKF 525A in the hepatotoxicity of antifungal drugs itraconazole and fluconazole in rats

Itraconazole and fluconazole are potent wide spectrum antifungal drugs. Both of these drugs induce hepatotoxicity clinically. The mechanism underlying the hepatotoxicity is unknown. The purpose of this study was to investigate the role of phenobarbital (PB), an inducer of cytochrome P450 (CYP), and SKF 525A, an inhibitor of CYP, in the mechanism of hepatotoxicity induced by these two drugs in vivo. Rats were pretreated with PB (75 mg/kg for 4 days) prior to itraconazole or fluconazole dosing (20 and 200 mg/kg for 4 days). In the inhibition study, for 4 consecutive days, rats were pretreated with SKF 525A (50 mg/kg) or saline followed by itraconazole or fluconazole (20 and 200 mg/kg) Dose-dependent increases in plasma alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma-GT), and alkaline phosphatase (ALP) activities and in liver weight were detected in rats receiving itraconazole treatment. Interestingly, pretreatment with PB prior to itraconazole reduced the ALT and gamma-GT activities and the liver weight of rats. No changes were observed in rats treated with fluconazole. Pretreatment with SKF 525A induced more severe hepatotoxicity for both itraconazole and fluconazole. CYP 3A activity was inhibited dose-dependently by itraconazole treatment. Itraconazole had no effects on the activity of CYP 1A and 2E. Fluconazole potently inhibited all three isoenzymes of CYP. PB plays a role in hepatoprotection to itraconazole-induced but not fluconazole-induced hepatotoxicity. SKF 525A enhanced the hepatotoxicity of both antifungal drugs in vivo. Therefore, it can be concluded that inhibition of CYP may play a key role in the mechanism of hepatotoxicity induced by itraconazole and fluconazole.