两性霉素B联合氟胞嘧啶与伏立康唑治疗艾滋病合并中枢神经系统新型隐球菌病的疗效分析

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中枢神经系统新型隐球菌病的疗效。方法24例艾滋病合并中枢神经系统新型隐球菌病患者,随机分为观察组和对照组,各12例,观察组患者使用两性霉素B联合氟胞嘧啶与伏立康唑进行治疗,对照组患者使用两性霉素B联合氟胞嘧啶进行治疗,比较两种治疗方式的临床疗效、患者的不良反应及患者的死亡率。结果经过治疗后观察组患者的治疗效果优于比对照组,比较差异具统计学意义（P〈0.05）。在不良反应和死亡率上两组比较差异无统计学意义（P〉0.05）。结论针对艾滋病合并中枢神经系统新型隐球菌病患者采用两性霉素B联合氟胞嘧啶与伏立康唑进行治疗,临床治疗效果更为显著,可明显减轻患者痛苦及改善临床症状。     

137例阴道真菌感染及耐药性分析

目的了解女性阴道中真菌感染及耐药情况。方法将白带常规中涂片镜检真菌阳性患者的阴道分泌物的标本进行培养、鉴定和药敏试验。结果 137份送检标本中,白色假丝酵母菌(84株,61.3%)检出率最高,其次是光滑球拟酵母菌(19株,13.9%),热带假丝酵母菌(15株,10.9%),克柔假丝酵母菌(7株,5.1%),其他真菌(12株,8.8%)。分离菌株对氟胞嘧啶,两性霉素B和伏立康唑的敏感率均>90%,伊曲康唑敏感率为84.7%,氟康唑敏感率为70.8%。结论女性阴道真菌感染的白色假丝酵母菌为主。氟胞嘧啶,两性霉素B和伏立康唑敏感率较高,氟康唑和伊曲康唑敏感率较低,但仍然有效。     

2014—2017年解放军总医院海南分院真菌分布及耐药性分析

目的 了解2014—2017年解放军总医院海南分院真菌的分布和耐药特点,为促进抗真菌药的合理应用、有效减缓真菌耐药提供参考。方法 提取解放军总医院海南分院2014年1月—2017年12月临床真菌分离和药敏相关数据,分析真菌的分布特征及其对常用抗真菌药的耐药率和变化趋势。结果 共纳入1 048份阳性真菌样本,呼吸道标本占41.89%,60岁以上患者（61.45%）和重症医学科（25.48%）分布比例最高;共分离出1 329株真菌,白色念珠菌、念珠菌属、热带念珠菌分别占24.53%、15.80%、13.69%。各种念珠菌对两性霉素B和5-氟胞嘧啶的敏感率基本保持在90%以上;热带念珠菌对伊曲康唑耐药率最高,达10%～20%,对氟康唑和伏立康唑的耐药率亦高于两性霉素B和5-氟胞嘧啶;白色念珠菌对伊曲康唑和伏立康唑的耐药率呈逐年快速上升趋势。结论 白色念珠菌和热带念珠菌感染应慎用唑类抗真菌药;两性霉素B和5-氟胞嘧啶是念珠菌感染的有效选择。     

2018-2022年深圳市妇幼保健院分离真菌的分布及耐药情况分析

目的 调查分析南方医科大学附属深圳妇幼保健院分离真菌的分布特点和药物敏感性情况,为妇幼真菌感染疾病的临床诊治、耐药性监测和流行病学研究提供参考。方法 回顾分析南方医科大学附属深圳妇幼保健院2018年1月-2022年12月标本采集、真菌鉴定和抗真菌药敏试验的结果数据。结果 共分离真菌3 350株,前2位分别为白色念珠菌1 542株、光滑念珠菌223株。阳性标本以阴道分泌物/宫颈分泌物为主。妇科和产科分离到的真菌最多。白色念珠菌对伊曲康唑、伏立康唑的5年耐药率分别为9.58%、4.12%,对两性霉素B和5-氟胞嘧啶的5年敏感率分别为99.79%、98.01%,对氟康唑的历年敏感率有逐渐升高的态势。光滑念珠菌、近平滑念珠菌和热带念珠菌对两性霉素B及5-氟胞嘧啶的敏感率均为100.00%。克柔念珠菌对两性霉素B和伏立康唑100.00%敏感。结论 南方医科大学附属深圳妇幼保健院分离真菌以念珠菌属为主,其中白色念珠菌最多。阴道分泌物/宫颈分泌物是主要真菌阳性分离标本。白色念珠菌对两性霉素B的耐药率最低、敏感率最高,对伊曲康唑的耐药率最高、敏感率最低。光滑念珠菌、近平滑念珠菌、热带念珠菌和克柔念珠菌对两性霉素B和5-氟胞嘧啶均无耐药性。光滑念珠菌对伊曲康唑耐药率最高、敏感率最低。     

泌尿系统感染念珠菌分布及耐药性分析

目的探讨泌尿道感染念珠菌的分布特点,抗真菌药物的耐药性,为临床治疗深部真菌感染提供实验室参考依据。方法中段尿标本接种科玛嘉真菌培养基,菌种鉴定及抗真菌药物敏感试验采用API试剂。结果2011年1月至2013年12月共分离出培养出112株念珠菌,其中白念珠菌占70.5%,热带念珠菌占13.4%。念珠菌对两性霉素B、氟胞嘧啶和伏立康唑敏感率均>90.0%,对氟康唑、伊曲康唑的敏感率有降低趋势。结论对于泌尿道感染念珠菌患者,应做真菌培养并根据药敏试验结果选择抗菌药物,治疗深部真菌感染应首选氟胞嘧啶和伏立康唑。     

重症监护病房院内肺部真菌感染100例的耐药菌分析

目的:对重症监护病房院内肺部真菌感染100例的病原菌分布和耐药菌进行分析,为临床合理用药提供指导.方法:选取我院于2013年1月～2017年1月收治的100例重症监护病房院内肺部真菌感染患者,对其临床资料进行回顾性分析,对病原菌进行分离和检测,并采用全自动微生物分析仪对病原菌进行药敏试验,分析耐药性.结果:100例患者均对痰液标本进行检测,共分离115株病原菌,主要为白色假丝酵母菌和热带假丝酵母菌;所有病原菌对伊曲康唑和氟康唑的耐药性较低,对氟胞嘧啶、两性霉素B以及伏立康唑的敏感性较高,分别为97.39％、96.52％和93.04％.结论:白色假丝酵母菌和热带假丝酵母菌是导致重症监护病房患者发生院内肺部真菌感染的主要致病菌,从其耐药性分析可以看出,在临床治疗中应首选伏立康唑、氟胞嘧啶以及两性霉素B,有助于提高治疗效果.     

药代动力学和药效动力学理论指导系统性抗真菌治疗

侵袭性真菌感染多见于有严重器官疾病、长期使用抗菌药物或免疫抑制人群,是住院患者常见的感染之一。目前,用于抗真菌治疗的药物数量较少,毒性较高。针对不同人群正确地进行抗真菌药物种类和剂量的选择非常重要。目前常用的抗真菌药物共有4类,它们是多烯类(两性霉素B)、唑类(氟康唑、伊曲康唑、伏立康唑)、嘧啶类(氟胞嘧啶)     

神经内科肺部真菌感染的发生原因和菌种及耐药性分析

目的了解我院神经内科肺部真菌感染原因、菌种、耐药以及预防情况,为治疗提供建议。方法住院的肺部的真菌感染患者317例,并对其感染的菌种,原因和耐药情况进行统计。结果317例肺部感染的患者中,分离的真菌依次为白色念珠菌181例（57．1％）、热带念珠菌52例（16．4％）、光滑念珠菌34例（10．7％）、克柔念珠菌26侧（8．2％）、其他念珠菌12株（3．7％）,曲霉菌属12株（3．7％）;造成肺部真菌感染的原因主要有脑出血和脑梗死等、脑膜炎等、合并慢性阻塞性肺病、合并意识障碍等;各种念珠菌对5种抗真菌药物的耐药率依次为两性霉素B为6（1．9％）,5-氟胞嘧啶为10（3．2％）,伏立康唑为18（5．7％）,伊曲康唑为54（17．0％）、氟康唑为84（26．5％）。结论神经内科患者肺部真菌感染以白色念珠菌为主,但是不能忽视其他真菌感染的治疗,两性霉素B对念珠菌的敏感性最好,5-氟胞嘧啶、伏立康唑对念珠菌属敏感性较高,伏立康唑和伊曲康唑对念珠菌的敏感性较差。医院应警惕真菌感染,加强支持治疗。     

156例白色念珠菌感染的特性及耐药性分析

目的通过分析不同标本中分离鉴定出的白色念珠菌,总结其临床分布情况和抗真菌药物敏感试验结果,为临床科室提供治疗真菌感染的依据。方法不同标本中鉴定分离出的156例白色念珠菌,对其在各类标本中的分布及耐药性进行分析;在标本来源方面痰液占第一位（70.5%）,尿液占第二位（18.1%）,分泌物占第三位（5.8%）,血液占第四位（3.9%）,其他占（1.7%）。结果经分离鉴定,156株白色念珠菌主要对两性霉素B、5-氟胞嘧啶和伏立康唑耐药性较低（0~25.4%）,对氟康唑和伊曲康唑耐药性较高（51.3%~69.9%）。结论 156株白色念珠菌感染部位的标本以呼吸道感染的痰液和泌尿道感染的尿液为主,两性霉素B、5-氟胞嘧啶和伏立康唑对白色念珠菌具有较低的耐药性,临床疗效明显;伊曲康唑和氟康唑对白色念珠菌的耐药性较高,应引起临床的注意,因此监测白色念珠菌的耐药性对临床用药有积极的指导作用。     

59例恶性血液病患者合并侵袭性真菌病的临床分析

目的观察59例恶性血液病合并侵袭性真菌病患者的临床特征,并探讨两性霉素B脂质体联合伏立康唑治疗恶性血液病患者合并侵袭性真菌病的临床疗效及安全性。方法回顾性分析2010年至2015年入住我院血液科合并侵袭性真菌病(IFI)的恶性血液病患者59例的病例资料,依据使用抗真菌药物的不同进行分组,其中17例应用两性霉素B脂质体联合伏立康唑治疗(联合治疗组),24例单用伏立康唑治疗(伏立康唑组),18例单用两性霉素B脂质体治疗(两性霉素B脂质体组)。收集、总结临床特征、分析其治疗效果及安全性,并进行统计学分析。结果联合治疗组的有效率为82.3%,伏立康唑组的有效率为37.5%,两性霉素B脂质体组的有效率为61.1%。三组之间治疗有效率差异均有统计学意义(P0.05)。而联合治疗组的不良反应发生率为58.8%,伏立康唑组的不良反应发生率为25.0%,两性霉素B脂质体组的不良反应发生率为55.5%。结论应用两性霉素B脂质体联合伏立康唑治疗恶性血液病合并侵袭性真菌病的效果较单用伏立康唑或单用两性霉素B脂质体,可明显提高疗效,且安全性上并不比单用两性霉素B脂质体差,患者往往能够耐受。     

Effect of antifungal treatment in a murine model of blastoschizomycosis

Blastoschizomyces capitatus is an emerging pathogenic fungus that can cause deep invasive diseases in neutropenic patients. We developed a model of disseminated blastoschizomycosis in immunosuppressed mice to evaluate the effectiveness of amphotericin B, flucytosine, fluconazole and voriconazole. High-dose fluconazole was the most effective drug at prolonging the survival of mice and at reducing fungal burden in the kidneys, spleen and liver.     

Economic evaluation of voriconazole in the treatment of invasive aspergillosis in the Netherlands

OBJECTIVE: To asses the cost-effectiveness of voriconazole in comparison to conventional amphotericin B and itraconazole for the treatment of invasive aspergillosis in the Netherlands. METHODS: The cost-effectiveness of voriconazole in comparison to conventional amphotericin B or itraconazole was evaluated with a decision tree model followed by a life-time Markov model, focusing on long-term survival of patients treated for invasive aspergillosis. Efficacy after 12 weeks of treatment from clinical trials was used to estimate long-term effectiveness by extrapolating these short-term results over time. Information on medical resource consumption, treatment pathways and switch proportions were obtained from both the literature and Experts. Probabilistic analysis was used to compare the cost-effectiveness among the regimens. RESULTS: With voriconazole, the mean cost for treating invasive aspergillosis per patient was E32 651 (2.5th percentile and 97.5th of uncertainty distribution: E30 037; E36 859), compared to E33 616 (E30 920; E39 633) for conventional amphotericin B and E29 115 (E23 537; E61 414) for itraconazole. The mean survival of patients treated with voriconazole was 174.0 life weeks (160.1; 188.8), compared to 116.1 life weeks (104.8; 128.0) for conventional amphotericin B and 150.4 life weeks (109.1; 194.4) for itraconazole. The beneficial effects of voriconazole on both cost and effectiveness compared with conventional amphotericin B resulted in a probability of 69.8% that voriconazole was a dominant treatment (i.e. less costs and longer survival). The incremental cost-effectiveness ratio of voriconazole versus itraconazole was E150 per life week (i.e. 7800 euros per life-year gained). Depending on the willingness to pay (WTP) the probability of being cost-effective vs. itraconazole increased to a maximum probability of 70%. CONCLUSION: In the treatment of invasive aspergillosis, voriconazole is dominant over amphotericin B and cost-effective in comparison to itraconazole.     

Economic evaluation of voriconazole in the treatment of invasive aspergillosis in the Netherlands

ABSTRACT

Objective: To asses the cost-effectiveness of voriconazole in comparison to conventional amphotericin B and itraconazole for the treatment of invasive aspergillosis in the Netherlands.

Methods: The cost-effectiveness of voriconazole in comparison to conventional amphotericin B or itraconazole was evaluated with a decision tree model followed by a life-time Markov model, focusing on long-term survival of patients treated for invasive aspergillosis. Efficacy after 12 weeks of treatment from clinical trials was used to estimate long-term effectiveness by extrapolating these short-term results over time. Information on medical resource consumption, treatment pathways and switch proportions were obtained from both the literature and Experts. Probabilistic analysis was used to compare the cost-effectiveness among the regimens.

Results: With voriconazole, the mean cost for treating invasive aspergillosis per patient was €32?651 (2.5th percentile and 97.5th of uncertainty distribution: €30?037; €36?859), compared to €33?616 (€30?920; €39?633) for conventional amphotericin B and €29?115 (€23?537; €61?414) for itraconazole. The mean survival of patients treated with voriconazole was 174.0 life weeks (160.1; 188.8), compared to 116.1 life weeks (104.8; 128.0) for conventional amphotericin B and 150.4 life weeks (109.1; 194.4) for itraconazole. The beneficial effects of voriconazole on both cost and effectiveness compared with conventional amphotericin B resulted in a probability of 69.8% that voriconazole was a dominant treatment (i.e. less costs and longer survival). The incremental cost-effectiveness ratio of voriconazole versus itraconazole was €150 per life week (i.e. 7800 euros per life-year gained). Depending on the willingness to pay (WTP) the probability of being cost-effective vs. itraconazole increased to a maximum probability of 70%.

Conclusion: In the treatment of invasive aspergillosis, voriconazole is dominant over amphotericin B and cost-effective in comparison to itraconazole.     

Fungal infections of the CNS: treatment strategies for the immunocompromised patient

Infections with fungi cause significant morbidity in the immunocompromised host and invasion of the CNS may lead to devastating consequences. Vulnerable individuals include those with haematological malignancies, transplant recipients, and those infected with HIV. Potential pathogens include yeasts, Aspergillus spp., other moulds of an increasing variety, and a range of dimorphic fungi, often associated with particular geographical locations. Antifungal treatments include polyenes such as amphotericin B and its lipid formulations, azoles such as fluconazole and itraconazole, and the more recent voriconazole and posaconazole. The new antifungal class of echinocandins, such as caspofungin, micafungin and anidulafungin, typically lack CNS penetration. Amphotericin B and flucytosine are used to initiate treatment for CNS yeast infections caused by Candida and Cryptococcus neoformans. Voriconazole is preferred for aspergillus, although amphotericin B, particularly in lipid formulation, is also useful. Reliable treatment data are lacking for CNS infections with most of the non-aspergillus moulds; posaconazole holds promise for the zygomycetes and perhaps some of the rarer pigmented fungi, but amphotericin B preparations are still recommended. Oral fluconazole is effective for the CNS manifestations of coccidioides, while histoplasmosis and blastomycoses typically require amphotericin B therapy. Effective treatment requires a definitive diagnosis, which is often challenging in the population at risk of CNS fungal infections.     

Comparative cost-effectiveness of voriconazole and amphotericin B in treatment of invasive pulmonary aspergillosis.

PURPOSE: The comparative cost-effectiveness of voriconazole and amphotericin B in the treatment of invasive pulmonary aspergillosis (IPA) was examined. METHODS: A decision-tree model was constructed comparing 12-week treatment outcomes in a subset of patients enrolled in a clinical trial comparing initial treatment of IPA with amphotericin B versus voriconazole. Patients included those with IPA who underwent a thoracic computed tomographic (CT) scan at baseline. Cost and survival were estimated for those with and without a halo sign at baseline. Incremental cost-effectiveness ratios comparing voriconazole with amphotericin B were calculated for both patient subgroups. RESULTS: Patients with a halo sign had similar costs and better survival rates than those without the sign. Within the subgroup of patients with the sign, total costs were lower and survival rates higher for those treated with voriconazole than for those treated with amphotericin B. For patients without a halo sign, total costs and survival rates were higher for those treated with voriconazole versus amphotericin B. CONCLUSION: Among patients treated for IPA, those with a baseline CT halo sign, an early indicator of the condition, appeared to have better survival rates and lower health care costs compared with patients without the sign. In patients with the halo sign, survival rates were higher and costs were lower when voriconazole rather than amphotericin B was used as first-line treatment; survival was better with voriconazole than with amphotericin B when the halo sign was not present. Voriconazole was cost-effective compared with amphotericin B when the halo sign was present, but voriconazole's cost-effectiveness when the sign was not present depended on the cost per life saved.     

Antifungal resistance in Candida spp. isolated in Italy between 2002 and 2005 from children and adults

The activity of amphotericin B, fluconazole, flucytosine, itraconazole and voriconazole was tested in vitro against 618 clinical Candida spp. isolates, using the broth microdilution or the disk diffusion method (voriconazole). Amphotericin B and voriconazole were the most potent antifungal agents assayed (100% of susceptible strains). Resistance to fluconazole and itraconazole was detected in three (0.7%) and 11 (2.7%) isolates of Candida albicans and in four (3.7%) isolates of Candida glabrata. Flucytosine intermediate, resistant strains, or both, were observed in C. albicans (0.3% and 0.7%), C. glabrata (2.8% intermediate) and C. tropicalis (15.2% and 15.2%). C. krusei was the least susceptible species to azoles. No statistically significant differences in the rates of resistant isolates depending on site of infection and age of the patient were observed, with the exception of C. albicans and itraconazole (higher percentage of resistance in children). At present, acquired antifungal resistance represents an uncommon finding in most Candida spp. circulating in Northern Italy.     

In vitro susceptibility testing of Candida and Aspergillus spp. to voriconazole and other antifungal agents using Etest: results of a French multicentre study

Minimum inhibitory concentrations (MICs) of the antifungal agent voriconazole were determined using the Etest and compared with those of amphotericin B, itraconazole and fluconazole using 1986 clinical isolates of Candida spp. Voriconazole MICs were also compared with those of amphotericin B and itraconazole using 391 clinical isolates of Aspergillus spp. Voriconazole was found to have more potent activity and lower MIC values than amphotericin B, itraconazole and fluconazole against C. albicans, C. tropicalis, C. parapsilosis and C. kefyr. Against C. glabrata and C. krusei, voriconazole was more active than either of the other two azole antifungals but had similar activity to amphotericin B. For species of Aspergillus, MIC values of voriconazole were lower than those of amphotericin B and itraconazole against A. fumigatus and A. flavus, and were similar to those of amphotericin B against A. niger. Against A. terreus, MIC values for voriconazole and itraconazole were similar. A. terreus is known to be resistant to amphotericin B, and this was reflected in higher MIC values compared with those of voriconazole and itraconazole. Voriconazole therefore compares very favourably with other antifungal agents against a large number of clinical isolates of Candida and Aspergillus spp.     

Clinical use of systemic antifungal agents

The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects, and drug interactions of amphotericin B, flucytosine, ketoconazole, and miconazole are reviewed. Amphotericin B, a heptaene compound with poor water solubility, disrupts the fungal cell wall by binding to ergosterol. Ketoconazole and miconazole, imidazole derivatives, are poorly water soluble and inhibit the synthesis of ergosterol. Flucytosine is a readily water-soluble, fluorinated pyrimidine agent that may be metabolized to fluorouracil. The pharmacokinetics of amphotericin B is unique and has not yet been clearly defined. After oral administration, absorption of flucytosine from the gastrointestinal tract is rapid and nearly complete. In adults, oral administration of ketoconazole produces peak concentrations of drug one to two hours after the dose. Miconazole is administered only intravenously and distributes well into most tissues. Amphotericin B remains the drug of choice for most systemic mycoses. Dosing of amphotericin B is often empiric and patient specific. Flucytosine is rarely used alone; the combination of flucytosine and amphotericin B exerts synergistic killing of many fungi. Ketoconazole is effective for treating many chronic fungal infections. Miconazole is seldom used because of the availability of agents that are equally effective, less toxic, or both. Nephrotoxicity can occur with amphotericin B therapy, while flucytosine is associated with gastrointestinal and hematologic toxicities. Ketoconazole is much less toxic than any of the other agents, while miconazole has a high incidence of adverse effects. In addition to the need for more effective and less toxic agents, research is needed to clearly define the pharmacokinetics and pharmacodynamics of currently available antifungal drugs.     

两性霉素B和5—氟胞嘧啶联合用药对肝、肾功能的影响

目的：探讨两性霉素B（AMB）和5－氟胞嘧啶（5－FC）联合治疗新型隐球菌性脑膜炎对肝、肾功能的影响。方法：用AMB联合5－FC治疗新型隐球菌性脑膜炎患赌40例,观察用药后肝、肾功能的变化。结果：治疗患 者中有75％（30／40）出现ALT升高,55％（22／40）出现AST升高,仅有12.5％（5／40）出现血清总胆红素升高。分别有47.5％（19／40）和20％（8／40）的患者出现血尿素氮和血肌酐异常。结论：AMB联合5－FC治疗新型隐球菌性脑膜炎对中毒性肝炎的发生率高,但不引起严重的中毒性肝损害。对肾脏的毒性表现为氮质血症,尿毒性的发生率低。     

非白念珠菌对常用抗真菌药物的敏感性分析

目的 了解非白念珠菌对我国常用抗真菌药物的耐药状况.方法 采用Roseo Neo-Sensitab纸片扩散法检测116株非念珠菌对常用抗真菌药物的敏感性.结果 除2株光滑念珠菌对两性霉素B耐药外,其它菌株均对两性霉素B敏感;86.4%的热带念珠菌和80%的近平滑念珠菌对氟康唑敏感;光滑念珠菌对两性霉素B、氟康唑和伊曲康唑的耐药率分别为3.6%、16.1%和10.7%;所有克柔念珠菌对氟康唑和氟胞嘧啶均耐药.结论 绝大多数非白念珠菌对两性霉素B敏感,克柔念珠菌对氟胞嘧啶及三唑类抗真菌药物的耐药率高,光滑念珠菌对常用抗真菌药物包括两性霉素B的敏感性低,对三唑类抗真菌药物的耐药率高,且对三唑类抗真菌药物存在交叉耐药.