两性霉素B联合氟胞嘧啶与伏立康唑治疗艾滋病合并隐球菌脑膜炎的临床回顾性研究

目的观察两性霉素B联合氟胞嘧啶与伏立康唑治疗艾滋病合并隐球菌性脑膜炎的疗效和安全性,探讨艾滋病合并隐球菌性脑膜炎的新型治疗策略。方法采用回顾性病例对照研究,20例艾滋病合并隐球菌脑膜炎分别接受三联治疗（两性霉素B＋氟胞嘧啶＋伏立康唑,n=10）和传统的两联治疗（两性霉素B＋氟胞嘧啶,n=10）,比较两种治疗方案在降低脑脊液中隐球菌计数的幅度以及临床症状缓解、病死率等方面的差异以及不良反应发生情况。结果治疗2周后,三联治疗患者脑脊液中隐球菌计数下降率明显高于两联治疗患者（下降率分别为0.743和0.408,P=0.009）,三联治疗患者头痛明显减轻或消失的时间短于两联治疗者（分别为12 d和20 d,P=0.009）,两组在2周、4周、8周及12周时的病死率均无统计学差异。两种治疗方案的不良反应发生率相当。结论两性霉素B联合氟胞嘧啶与伏立康唑能有效降低脑脊液中隐球菌计数,可作为艾滋病合并隐球菌脑膜炎诱导期的治疗选择。     

脂质体两性霉素B的临床应用进展

脂质体两性霉素B是在两性霉素B分子的外面包裹了生物性脂质体,通过脂质体的携带可改善药物在体内的分子代谢,较多地分布在肝、脾、肺,而在肾组织中分布减少,从而显著地减少了其不良反应,使患者的耐受性提高,临床疗效也获得了提高,适用于系统性真菌病患者的治疗。现就脂质体两性霉素B的临床应用作一综述。     

低氧对曲霉和假丝酵母体外两性霉素B、伊曲康唑和棘白素药敏试验的影响[英]／Warn PA…／／J Antimicrobial Chemother．

抗真菌药在体外和体内的效果有很大差异,可靠的体外药敏试验在对真菌病的用药是有帮助的。已知许多因素可影响真菌的最低抑菌浓度(MIC)测定,如培养基、菌悬液的浓度、试验方法的选择(多量稀释法或微量稀释法)和培养温度。作者研究了不同氧浓度对真菌体外药敏试验的影响。     

两性霉素B及其脂质体的抗真菌机制

自20世纪60年代发现两性霉素B以来,至今仍是最有效的抗真菌药物;但由于其对人体的毒副作用大而在临床上的应用受限。近年来,随着化疗、AIDS及器官移植患者的增多,临床真菌感染的病例呈上升趋势。相应的两性霉素B脂质体的出现也给临床提供了新的治疗手段。所以对两性霉素B及其脂质体作用机制的研究、探讨有着重要的临床意义。     

矾冰纳米乳对临床常见病原菌体外抗菌活性的研究

研究纳米化提高白矾与冰片复合物体外抗菌活性的效果。分别采用琼脂扩散法、体外杀菌试验及试管稀释法,测定白矾与冰片O/W型复合纳米乳对临床常见病原菌的体外抑菌、杀菌效果及最低抑菌浓度(MIC),实验中以等浓度矾冰液作为对照。结果显示,矾冰纳米乳对金黄色葡萄球菌、表皮葡萄球菌、大肠埃希菌、铜绿假单胞菌、白假丝酵母菌的抑制及杀灭活性均明显强于矾冰液(P0.05)。矾冰纳米乳对金黄色葡萄球菌、铜绿假单胞菌、大肠埃希菌临床菌株MIC90值分别为1.02、2.04和2.04 mg/mL,均明显低于矾冰液的MIC90值(P0.05)。上述实验结果提示,矾冰纳米乳与矾冰液均有广谱体外抑菌及杀菌活性,白矾及冰片复合物纳米化可提高抗菌效果。     

金黄色葡萄球菌体外抗菌活性分析

抗生素在临床上已广泛应用了数十年 ,在抗感染疾病中发挥了极其重要的作用 ,特别是金黄色葡萄球菌耐药菌株相继出现 ,给临床治疗带来困难。目前已知这种耐药是由位于染色体外的 DNA上的耐药基因所编码 ,并通过接合、转导和转化等方式在细菌间传播 ,其中以接合为最主要。同时在传播过程中 ,这种耐药基因又可不断重新组成新的耐药基因而产生对多种抗生素同时耐药的多重耐药菌株。因此本文对174株金黄色葡萄球菌的耐药机理及抗生素耐药性进行研究 ,对如何减少耐药菌株的产生控制医院内感染的流行 ,指导临床治疗有着一定的意义。1　材料与方法…     

1例两性霉素B治疗SLE真菌性肺炎的护理体会

两性霉素B可用于治疗真菌性肺炎,但其副作用较大。本文总结了1例使用两性霉素B治疗SLE真菌性肺炎的护理。包括对患者症状及心理状态的评估,严格遵循两性霉素B的用药方法及药物使用注意事项,对患者进行标准的用药护理及其他的对症护理。认为对于真菌性肺炎患者,给予相关的护理干预,对疾病的治愈康复有重要意义。     

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.     

两性霉素B治疗侵袭性肺部真菌感染的临床分析

目的 分析两性霉素B治疗ICU内侵袭性真菌感染的疗效与不良反应.方法 回顾性分析98例合并侵袭性肺部真菌感染的重症患者接受两性霉素B微泵静脉给药的临床资料.结果 两性霉素B的临床有效率77.55％,真菌清除率75.51％.不良反应包括寒战发热（9.18％）、皮疹（4.08％）、静脉炎（1.02％）、恶心呕吐（6.12％）、低钾血症（16.32％）、肝损害（1.02％）和肾损害（4.08％）.结论 国产两性霉素B对于重症患者侵袭性真菌感染疗效确定,采用持续微泵静脉给药不良反应发生率低.     

伏立康唑治疗深部真菌感染的观察及护理

近年来由于肿瘤化疗、器官移植等免疫缺陷患者增多,以及广谱抗生素、肾上腺皮质激素、免疫抑制剂等药物的广泛应用,深部真菌感染呈持续增多趋势.伏立康唑作为新的第二代三唑类广谱抗真菌药,在体内、外的抗真菌活性强,已广泛应用于临床,并取得了一定疗效.我科于2009年5月～2011年5月应用伏立康唑对33例确诊为深部真菌感染的患者进行治疗,效果较好,现将护理体会报道如下.     

泊沙康唑对临床来源接合菌的体外抗菌活性研究

目的研究泊沙康唑对临床来源的接合菌体外抗菌活性。方法对临床来源的43株接合菌采用ITS区序列分析进行准确鉴定,采用E-test纸片法研究泊沙康唑对43株菌的体外药物敏感性,观察其MIC值。结果经ITS序列分析鉴定,43株临床来源接合菌中最为常见的是小孢根霉和不规则毛霉(各12株),其次为米根霉(10株),ramosa(3株)。其他菌种分别为ornata、总状共头霉、微小根毛霉、卷曲毛霉、印度毛霉和冻土毛霉各1株。E-test纸片法测得泊沙康唑对毛霉属、根霉属和Lichtheimia spp.的MIC值范围分别为0.19～>32μg/mL、0.19～3μg/mL、0.002～0.38μg/mL,对总状共头霉和微小根毛霉的MIC值分别为1μg/mL和0.19μg/mL。结论泊沙康唑对大部分接合菌有效,不同种属MIC值范围不同,毛霉属真菌的MIC值差异较大。     

In vitro antifungal activity of voriconazole against dermatophytes and superficial isolates of Scopulariopsis brevicaulis

We have studied the in vitro antifungal activity of voriconazole, fluconazole and itraconazole against 252 clinical isolates of dermatophytes and Scopulariopsis brevicaulis by a standardized agar diffusion method (NeoSensitabs). Several important factors such as temperature (28 degrees C vs. 35 degrees C) and incubation time (2-10 days vs. 18-74 h) were adapted to dermatophytes and Scopulariopsis requirements. Voriconazole showed an excellent activity against most species of dermatophytes, higher than itraconazole and fluconazole. However, S. brevicaulis isolates were highly resistant to all azoles used in this study. Voriconazole might be an interesting antifungal alternative to refractory superficial mycoses.     

In vitro activities of voriconazole, fluconazole, itraconazole and amphotericin B against non Candida albicans yeast isolates

Antifungal susceptibility testing was performed on 197 yeast isolates from the BCCM/IHEM biomedical fungi and yeasts collection (Belgian Co-ordinated Collections of Micro-organisms / IPH-Mycology) to study the in vitro activity of voriconazole against fluconazole, itraconazole and amphotericin B. MICs of the four antifungal agents were determined by an adapted NCCLS M27-A microdilution reference method. MIC readings were visually and spectrophotometrically determined. Optical density data were used for calculation of the MIC endpoints. For amphotericin B, the MIC endpoint was defined as the minimal antifungal concentration that exerts 90% inhibition, compared to the control growth. The azoles endpoints were determined at 50% inhibition of growth. The MIC distribution of voriconazole susceptibilities showed that 193 isolates had a MIC < or = 2 microg/ml and 185 a MIC < or = 1 microg/ml. Cross-tabulation of voriconazole, fluconazole, and itraconazole MICs indicated that voriconazole MICs raised with fluconazole and itraconazole MICs. The in vitro data obtained in this study suggest that voriconazole may also be effective treating yeast infection in patients infected with fluconazole or itraconazole resistant isolates.     

In vitro activity of fluconazole and amphotericin B against Candida inconspicua clinical isolates as determined by the time-kill method

Candida inconspicua is an emerging pathogen in immunocompromised patients possessing inherently decreased susceptibility to fluconazole. We determined the MICs and killing activity of fluconazole and amphotericin B against C. inconspicua clinical isolates as well as reference strain C. inconspicua ATCC 16783 for comparison. MICs were determined using the standard broth microdilution method. Killing rates were determined using time-kill methodology at 0.5-16 x MIC fluconazole and amphotericin B concentrations. Fluconazole and amphotericin B MIC values varied between 16-128 mg/l and 0.5-1 mg/l, respectively. In time kill-assays fluconazole showed fungistatic effect at 1-16 x MIC concentrations against all tested strains after 24 h-incubation, but became fungicidal after 48 h at 4-16 x MIC concentrations. The time necessary to achieve fungicidal endpoint at 1 mg/l amphotericin B concentration ranged from 2 to 24 h. Our in vitro results confirm the data that fluconazole is ineffective against C. inconspicua at the fluconazole serum concentration attainable in humans. Amphotericin B due to its rapid killing activity seems to be a good alternative for the treatment of infections caused by C. inconspicua.     

In vitro activity of amphotericin B cochleates against Leishmania chagasi

Cochleate delivery vehicles are a novel lipid-based system with potential for delivery of amphotericin B (AmB). In this study, the efficacy of cochleates was evaluated by examining the in vitro activity of AmB cochleates (CAMB) against Leishmania chagasi in a macrophage model of infection. We demonstrate that CAMB is nontoxic to macrophages at concentrations as high as 2.5 μg/mL, whereas the conventional formulation, AmB deoxycholate, showed high toxicity at this concentration. The in vitro activity of CAMB against L. chagasi was found to be similar to that of the reference drug AmB deoxycholate, with ED50s of 0.017 μg/mL and 0.021 μg/mL, respectively. Considering that L. chagasi affects organs amenable to cochleate-mediated delivery of AmB, we hypothesize that CAMB will be an effective lipid system for the treatment of visceral leishmaniasis.     

The activity of echinocandins, amphotericin B and voriconazole against fluconazole-susceptible and fluconazole-resistant Brazilian Candida glabrata isolates

The extensive use of azole antifungal agents has promoted the resistance of Candida spp to these drugs. Candida glabrata is a problematic yeast because it presents a high degree of primary or secondary resistance to fluconazole. In Brazil, C. glabrata has been less studied than other species. In this paper, we compared the activity of three major classes of antifungal agents (azoles, echinocandins and polyenes) against fluconazole-susceptible (FS) and fluconazole-resistant (FR) C. glabrata strains. Cross-resistance between fluconazole and voriconazole was remarkable. Among the antifungal agents, the echinocandins were the most effective against FS and FR C. glabrata and micafungin showed the lowest minimal inhibitory concentrations.     

布洛芬对曲霉的体外抗真菌活性评价

目的观察布洛芬对曲霉临床分离株的体外抗真菌活性。方法分别用微量液基稀释法和纸片扩散法,测定布洛芬对10株烟曲霉、黄曲霉和土曲霉的抗菌活性。结果微量液基稀释法显示布洛芬对曲霉的最低抑菌浓度（MIC）范围为1000～2000μg/mL,最低杀菌浓度（MFC）范围为2000～8000μg/mL;纸片扩散法也显示布洛芬有体外抗曲霉活性：48h时,1000μg布洛芬对曲霉产生的抑菌圈直径为（20.1±3.89）mm。结论布洛芬有体外抗曲霉活性。     

In vitro interaction between glabridin and voriconazole against Aspergillus fumigatus isolates

BackgroundVoriconazole (VRC) is widely recommended as the first-line therapy for invasive aspergillosis. However, surveillance studies have demonstrated that there is an increase in the frequency of azole resistance among Aspergillus fumigates isolates. In recent years, more studies on effective synergisms between natural agents and antifungal drugs have been published.AimsTo evaluate the synergistic antifungal effect of glabridin (Gla) and VRC against A. fumigatus isolates.MethodsPotential interactions between Gla and VRC were studied by using a microdilution checkerboard method based on the CLSI reference technique. To assess the interaction of drugs the fractional inhibitory concentration index (FICI) was calculated based on the Loewe Additivity model.ResultsThe minimum inhibitory concentrations (MIC) obtained with Gla alone were relatively high (MIC₅₀ 16 μg/ml). However, our results showed synergistic interaction between Gla and VRC against A. fumigatus strains, with FICI range values between 0.15 and 0.5.ConclusionsSynergistic activity of Gla and VRC against both VRC-sensitive and -resistant A. fumigatus isolates may lead to design new antifungal agents, especially for inhibiting those azole-resistant strains.