抗真菌新药卡泊芬净在血液病患者经验性抗真菌治疗中的疗效观察

目的 探讨卡泊芬净在血液病患者经验性抗真菌治疗中的疗效.方法 将2008年10月至2010年10月收治的40例抗生素治疗无效且怀疑真菌感染的血液病患者随机分为两组,各20例,A组给予卡泊芬净治疗,第1天70 mg静脉滴注,第2天起50 mg静脉滴注;B组患者给予脂质体两性霉素B治疗,3 mg/(kg·d)静脉滴注.两组均治疗10 d,观察两组患者的疗效和不良反应.结果两组总有效率比较(66.7% vs.61.1%),差异无统计学意义(χ2=1.17,P>0.05),但A组肾毒性、输液反应发生率明显低于B组(χ2=4.37,4.37,P<0.05).结论 卡泊芬净用于血液病患者经验性抗真菌治疗,效果较好,患者耐受性较好,是侵袭性真菌感染的一个较好选择.     

新型抗真菌药卡泊芬净

Echinocandins是新一类抗真菌药 ,通过非竞争性抑制 1 ,3 β D肽聚糖合成酶而阻止真菌细胞壁合成。此类药物毒性低 ,对大多数分离的念珠菌属均有快速杀菌作用 ,且因其良好的药代动力学特性而可每日 1次给药 ,故具有较好的临床应用前景。卡泊芬净 (Caspofunginacetate ,亦称MK 0 991 ,L 74 3,872 )是第一个批准用于临床的棘白菌素 (echinocan din)。一、药理作用卡泊芬净是一种半合成脂肽 ,属 1 6环脂肽[1] 。通过非竞争性抑制 1 ,3 β D肽聚糖合成酶而抑制真菌细胞壁合成[2 ] 。 1 ,3 β D肽聚糖合成酶催化真菌细胞壁多聚葡聚糖的合成 ,…     

注射用醋酸卡泊芬净与注射用替考拉宁存在配伍禁忌

随着新药的不断出现,有些药物之间是否存在配伍禁忌无法在《静脉药物配伍禁忌表》中查获。2007年12月,笔者在临床应用注射用醋酸卡泊芬净钠与注射用替考拉宁连续静脉滴注时出现药物性状改变,现报道如下。     

注射用醋酸卡泊芬净与克林霉素磷酸酯注射液存在配伍禁忌

在临床中我们发现注射用醋酸卡泊芬净（科赛斯）与克林霉素磷酸酯注射液之间存在配伍禁忌，现报道如下。     

卡泊芬净治疗急性白血病并发真菌感染10例临床分析

我们选择因心脏、肾脏功能有损害或年龄≥70岁或因其他抗真菌药物治疗失败的急性白血病患者合并真菌感染的使用卡泊芬净治疗观察临床疗效和不良反应。1资料与方法1.1病例选择按照中国侵袭性真菌感染工作组制定的血液病/恶性肿瘤患者侵袭性真菌感染的诊断标准[1],10例中确诊5例,     

醋酸卡泊芬净与多烯磷脂酰胆碱注射液存在配伍禁忌

醋酸卡泊芬净（商品名科赛斯）为白色或类白色冻干块状物，在无菌条件下加入无菌注射用水，配制后为透明澄清液体，常用于治疗对其他药物治疗无效或不能耐受的侵袭性曲霉菌病。多烯磷脂酰胆碱注射液（商品名易善复），为黄色澄清液体，用于治疗各种类型的肝病，如肝炎、肝硬化、肝昏迷等。2008年6月在使用醋酸卡泊芬净与多烯磷脂酰胆碱注射液时发现这两种药物之间存在配伍禁忌，现报道如下。     

注射用醋酸卡泊芬净与注射用甲泼尼龙琥珀酸钠存在配伍禁忌

科赛斯（通用名称：注射用醋酸卡泊芬净）主要适用于治疗对其他治疗无效或不能耐受的侵袭性曲霉菌病;对疑似真菌感染的粒细胞缺乏症伴发热患者的经验治疗;亦可治疗侵袭性念珠菌病,包括中性粒细胞减少症及非中性粒细胞减少症患者的念珠菌血症。甲泼尼龙（通用名称：注射用甲泼尼龙琥珀酸钠）主要适用于器官移植排异反应、免疫综合征（抑制免疫作用）,亦可用于急性肾上腺皮质功能不全、休克等。     

卡泊芬净联合其他抗真菌药物治疗血液病嗜中性粒细胞缺乏合并侵袭性真菌感染疗效观察

目的 分析评价卡泊芬净联合其他抗真菌药物治疗恶性血液病患者中性粒细胞缺乏时合并侵袭性真菌感染的有效性和安全性.方法 选择2005年6月至2007年6月应用卡泊芬净联合其他抗真菌药物治疗恶性血液病患者嗜中性粒细胞缺乏时合并侵袭性真菌感染16例(20例次)患者.16例患者急性淋巴细胞白血病3例,多发性骨髓瘤3例,急性非淋巴细胞白血病5例,淋巴瘤5例.其中确诊侵袭性真菌感染3例,临床诊断8例,拟诊5例.患者第1天用负荷剂量卡泊芬净70 mg静脉滴注,第2天开始用50mg,每日1次,直至血象上升或症状好转后改口服其他抗真菌药,在用卡泊芬净同时联合应用其他抗真菌药(两性霉素B,或伏立康唑,或伊曲康唑),连用7～10 d停用其他抗真菌药,卡泊芬净至少应用7 d,最长应用57 d.平均应用14 d.所有患者在发热时均行真菌抗原检测及其血培养、痰培养,均行胸部CT检查,治疗结束进行疗效评估.治疗成功包括完全反应和部分反应.结果 16例(20例次)患者有17次出现血氧饱和度下降.经联合用药后1～6 d血氧饱和度恢复正常,3次为临床诊断患者大剂量化疗或造血干细胞移植期间治疗用药.16例患者抢救治疗成功率100%,应用卡泊芬净治疗期间未见明显不良反应.结论 对于危重血液病患者粒细胞缺乏期卡泊芬净联合其他抗真菌药物治疗重度侵袭性真菌感染,疗效可靠,副作用小,具有临床应用价值.     

卡泊芬净在中性粒细胞缺乏伴持续发热患者经验性抗真菌治疗中的疗效观察

卡泊芬净(caspofungin acetate.亦称MK20991,L2743872)是第一个批准用于临床的棘白菌素。此类药物毒性低,对大多数临床分离的念珠菌属和曲霉属均有快速杀菌作用。在血液科恶性肿瘤接受化疗或进行造血干细胞移植、再生障碍性贫血等发生中性粒细胞缺乏的患者中,侵袭性真菌感染是其重要的死亡原因。本研究报道6例中性粒细胞缺乏患者经验性应用卡泊芬净的疗效与不良反应。     

卡泊芬净联合伊曲康唑治疗侵袭性肺部真菌感染的效果分析

目的评价醋酸卡泊芬净联合伊曲康唑治疗侵袭性肺部真菌感染的疗效与安全性。方法侵袭性肺部真菌感染患者35例,应用计算机随机分为两组,治疗组18例,给予醋酸卡泊芬净静脉滴注,首日70mg,次日起50mg／d,患者临床症状基本消失且体温正常5d、或连续痰标本涂片阴性后3d改为口服伊曲康唑胶囊200mg／d;对照组17例,静脉滴注伊曲康唑注射液,第1、2天每日2次,每次200mg,以后每日1次,每次200mg,连续12d;14d后改为口服伊曲康唑胶囊200mg／d。两组均以患者的临床症状、影像学和痰及肺泡灌洗液真菌连续培养均正常1周以上等作为停药指标。观察两组患者的疗效与不良反应发生情况。结果治疗组治愈8例,显效6例,总有效率为77．78％（14／18）;对照组治愈5例,显效6例,总有效率为64．30％（11／17）,两组总有效率差异有统计学意义（X^2=27．41,P=0．03）;治疗组与对照组不良反应各有2例,差异无统计学意义（P〉0．05）。结论两种方案对侵袭性肺部真菌感染均有效,卡泊芬净静脉滴注后2—4周口服伊曲康唑有较好的疗效,且安全性好。     

Caspofungin: an echinocandin antifungal agent

BACKGROUND: The mainstays of treatment for nosocomial fungal infections have been amphotericin B and azole derivatives. Caspofungin acetate is a new echinocandin antifungal agent with a mechanism of action that targets a structural component of the fungal cell wall. OBJECTIVE: This article describes the pharmacologic properties and potential clinical usefulness of caspofungin. METHODS: Relevant information was identified through searches of MEDLINE (1966-September 2001). Iowa Drug Information Service (1966-September 2001), and International Pharmaceutical Abstracts (1970-September 2001), as well as meeting abstracts of the Infectious Diseases Society of America and the Interscience Conference on Antimicrobial Agents and Chemotherapy (1996-2001), using the terms caspofungin, MK-0991, pneumocandin, echinocandin, candin, and beta-(1,3)-glucan inhibitor. RESULTS: In vitro, caspofungin exhibits antifungal activity against an array of clinically important yeasts and molds, including Candida and Aspergillus spp. The proposed susceptibility breakpoint for caspofungin against Candida spp, the most common cause of nosocomial fungal infections, is a minimum inhibitory concentration of < or =1 microg/mL. In humans, caspofungin has a volume of distribution of 9.67 L, is extensively bound to albumin (97%), has a plasma elimination half-life of 9 to 11 hours, and is metabolized to inactive metabolites in the liver. Dose adjustment based on age, sex, race, or renal function does not appear to be necessary, although patients with moderate hepatic insufficiency (Child-Pugh score 7-9) should receive a lower maintenance dose. The results of clinical trials, although somewhat preliminary, suggest that caspofungin is effective in the treatment of esophageal and oropharyngeal candidiasis and invasive aspergillosis. When combined with other antifungal agents, caspofungin produces a synergistic or additive effect against a variety of clinically important fungi. The most commonly reported adverse events with caspofungin have included fever, infusion-related reactions, headache, nausea, elevations in liver transaminase levels, and histamine-type reactions. The recommended dosage in adults is 70 mg IV on day 1 followed by 50 mg/d, with the duration of treatment depending on the severity of the patient's underlying condition and the clinical response. CONCLUSION: Although additional studies are needed, caspofungin appears to be a promising agent for the treatment of patients with difficult-to-treat or life-threatening fungal infections.     

Caspofungin: the first representative of a new antifungal class

Caspofungin (MK-0991; L-743,872) belongs to the echinocandin family, a new class of antifungal agents that act on the fungal cell wall by inhibiting glucan synthesis. Data in vitro, and experimental studies, have demonstrated that caspofungin has antifungal activity against yeasts of the genus Candida (including isolates resistant to azoles and amphotericin B), several species of filamentous fungi, including Aspergillus, and certain dimorphic fungi, such as Histoplasma, Blastomyces and Coccidioides. In vitro and in animals, caspofungin shows additive or synergic antifungal activity with amphotericin B and triazoles. It also possesses activity against Pneumocystis carinii. Clinical trials have shown caspofungin to be well tolerated and effective in invasive aspergillosis in patients refractory or intolerant to standard treatment (45% favourable responses), in oropharyngeal and oesophageal candidiasis (67-93% favourable responses with an efficacy similar to those of amphotericin B and fluconazole), and in invasive candidiasis with efficacy equivalent to that of amphotericin B, and better tolerability. The results of these first clinical trials were promising, and led to the approval of caspofungin for invasive aspergillosis after failure of, or intolerance to, standard therapy. Further studies are required to define the exact role of caspofungin in the antifungal armamentarium.     

Voriconazole: a new triazole antifungal agent

OBJECTIVE: To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. DATA SOURCES: A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. DATA EXTRACTION: All published and unpublished trials and abstracts citing voriconazole were selected. DATA SYNTHESIS: Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. CONCLUSIONS: Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.     

Terconazole--a new antifungal agent for vulvovaginal candidiasis

Terconazole is a new broad-spectrum antifungal agent for the treatment of vulvovaginal candidiasis. Instead of an imidazole structure, terconazole contains a triazole ring, a structure developed specifically to improve antifungal activity. Clinical studies of this antifungal agent have involved 5,500 women worldwide and a number of terconazole formulations, including 80-mg vaginal suppositories and 0.4% vaginal cream. The highlights of several large, major studies are discussed in this review article. In European studies, mycologic cure rates for terconazole regimens approached or exceeded 90%. Speed of action was rapid, and relapse rates were low. In double-blind, multicenter studies conducted in the United States, clinical cure rates for 0.4% terconazole cream ranged from 86% to 96% and microbiologic cure rates from 77% to 91% at 8 to 10 days after therapy. Most patients remained free of positive signs and symptoms and microbiologic evidence of infection at 30 to 35 days posttherapy. Symptomatic relief tended to be more rapid for patients treated with 0.4% terconazole cream than for those treated with 2.0% miconazole nitrate cream. In US studies of 80-mg terconazole suppositories, clinical cure rates 8 to 10 days after therapy were between 89% and 92%, and microbiologic cure rates were between 80% and 85%. Relapse rates were also low with this form of therapy. No statistically significant differences were found between three days of treatment with 80-mg terconazole suppositories and seven days of treatment with 100-mg miconazole nitrate suppositories. This research demonstrates that terconazole is a fast-acting, highly effective, well-tolerated therapy for vulvovaginal candidiasis.     

In vitro activity of naftifine, a new antifungal agent.

Naftifine exhibits an interesting in vitro spectrum of activity against dermatophytes (38 strains; minimal inhibitory concentration [MIC] range 0.1 to 0.2 microgram/ml), aspergilli (6 strains; MIC range, 0.8 to 12.5 microgram/ml), Sporothrix schenckii (2 strains; MICs, 0.8 and 1.5 microgram/ml), and yeasts of the genus Candida (77 strains; MIC range, 1.5 to greater than 100 microgram/ml). Its degree of efficacy is unaffected by the organism density in the test medium, and it is primarily fungicidal against dermatophytes as well as yeasts. Its in vitro efficacy is pH dependent and rises with increasing pH values.     

Bioassay for SF 86-327, a new antifungal agent.

A bioassay with Trichophyton mentagrophytes is described for SF 86-327, an allylamine antifungal agent. SF 86-327 serum concentrations were measured by bioassay in 117 serum sampler from five patients receiving 500 mg/day. The peak, trough, and area under the concentration-time curve were determined after the first dose and at steady state. Drug accumulation occurred with prolonged therapy.     

In vitro activity of ME1401, a new antifungal agent.

The in vitro antifungal activity of ME1401, a potential topical antifungal agent, was compared with that of haloprogin, clotrimazole, miconazole, tolnaftate, and ciclopirox olamine by using an agar dilution procedure. ME1401 showed a broad antifungal spectrum and inhibited all of the 428 strains of 52 species of pathogenic yeasts and filamentous fungi tested at concentrations ranging from 0.01 to 12.5 micrograms/ml. In general, the activity of ME1401 was comparable or superior to that of clotrimazole and was greater than that of haloprogin and the other reference drugs under the conditions used. Only tolnaftate was superior to ME1401 in its activity against clinical isolates of Trichophyton rubrum. ME1401 showed no cross-resistance with any of the reference drugs and exhibited potent fungicidal activity.     

Anidulafungin: review of a new echinocandin antifungal agent

Anidulafungin (Vicuron Pharmaceuticals) is a new echinocandin antifungal with potent activity against Aspergillus and Candida spp. Anidulafungin is a noncompetitive inhibitor of (1,3)-β-d-glucan synthase within fungal cells. The drug is rapidly distributed and steady-state concentrations are achieved after the first dose, when a loading dose of twice the daily maintenance dose is given on day 1. Drug biotransformation occurs via chemical degradation, with no hepatic metabolism or renal elimination. A favorable pharmacokinetic profile and lack of significant drug interactions suggest that patients can receive anidulafungin without dosage adjustments. These characteristics, in addition to comparable efficacy to fluconazole (Diflucan^®, Pfizer Ltd) in the treatment of esophageal candidiasis, support further investigation of its use in the treatment of systemic fungal infections caused by Candida and Aspergillus spp.     

Anidulafungin: review of a new echinocandin antifungal agent

Anidulafungin (Vicuron Pharmaceuticals) is a new echinocandin antifungal with potent activity against Aspergillus and Candida spp. Anidulafungin is a noncompetitive inhibitor of (1,3)-beta-D-glucan synthase within fungal cells. The drug is rapidly distributed and steady-state concentrations are achieved after the first dose, when a loading dose of twice the daily maintenance dose is given on day 1. Drug biotransformation occurs via chemical degradation, with no hepatic metabolism or renal elimination. A favorable pharmacokinetic profile and lack of significant drug interactions suggest that patients can receive anidulafungin without dosage adjustments. These characteristics, in addition to comparable efficacy to fluconazole (Diflucan, Pfizer Ltd) in the treatment of esophageal candidiasis, support further investigation of its use in the treatment of systemic fungal infections caused by Candida and Aspergillus spp.     

A chemically modified tetracycline (CMT-3) is a new antifungal agent

Several chemically modified tetracycline analogs (CMTs), which were chemically modified to eliminate their antibacterial efficacy, were unexpectedly found to have antifungal properties. Of 10 CMTs screened in vitro, all exhibited antifungal activities, although their efficacies varied. Among these compounds, CMT-315, -3, and -308 were found to be the most potent as antifungal agents. The MICs of CMT-3 against 47 strains of fungi in vitro were determined by using amphotericin B (AMB) and doxycycline as positive and negative controls, respectively. The MICs of CMT-3 were generally found to be between 0.25 and 8.00 microg/ml, a range that approximates the blood levels of this drug when administrated orally to humans. Of all the yeast species tested to date, Candida albicans showed the greatest sensitivity to CMT-3. The filamentous species most susceptible to CMT-3 were found to be Epidermophyton floccosum, Microsporum gypseum, Pseudallescheria boydii, a Penicillium sp., Scedosporium apiospermum, a Tricothecium sp., and Trichophyton rubrum. Growth inhibition of C. albicans by CMT-3, determined by a turbidity assay, indicated a 50% inhibitory concentration of 1 microg/ml. Thirty-nine strains, including 20 yeasts and 19 molds, were used to measure viability (the ability to grow after treatment with a drug) inhibition by CMT-3 and AMB. CMT-3 exhibited fungicidal activity against most of these fungi, especially the filamentous fungi. Eighty-four percent (16 of 19) of the filamentous fungi tested showed more than 90% inhibition of viability by CMT-3. In contrast, AMB showed fungicidal activity against all yeasts tested. However, most of the filamentous fungi (16 of 19) showed less than 50% inhibition of viability by AMB, indicating that AMB is fungistatic against most of these filamentous fungi. To begin to identify the sites in fungal cells affected by CMT-3, C. albicans and a Penicillium sp. were incubated with the compound at 35 degrees C, and then the fluorescence of CMT-3 was observed by confocal laser scanning electron microscopy. CMT-3 appeared to have widespread intracellular distribution throughout C. albicans and the Penicillium sp. The mechanisms of the antifungal activity of CMT-3 are now being explored.