LC-MS同时测定醋酸卡泊芬净中的3种杂质

目的 建立同时测定醋酸卡泊芬净中杂质A、C和D的LC-MS方法。方法 色谱柱为WatersCORTECS^?C₁₈⁺(4.6 mm×150 mm,2.7μm)色谱柱;流动相A为0.1%甲酸-水溶液,流动相B为0.1%甲酸-乙腈;用电喷雾离子化单四极杆质谱,以选择离子检测方式对杂质A和C进行正离子检测,对杂质D进行负离子检测。结果 杂质A、C和D在线性范围内线性系数r≥0.999 3;平均回收率分别为100.5%,104.1%和105.2%,RSD<4%(n=6);按S/N=10计算,杂质A、C和D的定量限分别为31.8,6.99,15.5 ng·mL^-1。3批样品中杂质A、C和D的含量均低于限度值。结论 该方法简单、灵敏度高、适用性强,可用于醋酸卡泊芬净中杂质A、C和D的同时定量检测,并可为醋酸卡泊芬净中其他杂质检测提供参考。     

Echinocandins: Their Role in the Management of Candida Biofilms

The importance of antifungal agents and their clinical implications has received little attention in comparison to antibiotics, particularly in the health-care setting. However, apart from bacterial infections rising in hospitals, the incidences of fungal infections are growing with the development of resistance to conventional antifungal agents. Newer antifungal agents such as echinocandins (ECs) have been extensively studied over the past decade and are recognised as a superior treatment compared with prior antifungals as a first line of therapy in tertiary institutions. Caspofungin (CAS), micafungin (MICA) and anidulafungin (ANID) are the three most widely used EC antifungal agents. The treatment of biofilm-associated fungal infections affecting patients in tertiary health-care facilities has been identified as a challenge, particularly in Indian Intensive Care Unit (ICU) settings. With the rising number of critically ill patients requiring invasive devices such as central venous catheters for treatment, especially in ICUs, these devices serve as a potential source of nosocomial infections. Candida spp. colonisation is a major precursor of these infections and further complicates and prolongs treatment procedures, adding to increasing costs both for hospitals and the patient. Analysing studies involving the use of these agents can help in making critical decisions for antifungal therapy in the event of a fungal infection in the ICU. In addition, the development of resistance to antifungal agents is a crucial factor for assessing the appropriate antifungals that can be used for treatment. This review provides an overview of ANID in biofilms, along with CAS and MICA, in terms of clinical efficacy, resistance development and potency, primarily against Candida spp.     

氨基丁酸联合卡泊芬净的体外抗白色假丝酵母菌协同作用研究

目的探讨氨基丁酸联合卡泊芬净体外抗白色假丝酵母菌的协同作用。方法采用CLSI公布的M27-A方案微量棋盘液基稀释法测定氨基丁酸单用以及联合卡泊芬净对白色假丝酵母菌标准株SC5314的MIC80值和FICI值。采用抗真菌试管敏感性实验,考察给药24h后,卡泊芬净单用以及氨基丁酸联合卡泊芬净对白色假丝酵母菌SC5314生长的影响。采用生长曲线实验,测定氨基丁酸联合卡泊芬净抗白色假丝酵母菌SC5314的生长曲线。结果氨基丁酸单用对白色假丝酵母菌SC5314的MIC80>20μmol·L-1,说明氨基丁酸单用对SC5314没有抑菌作用;但1.25μmol·L-1氨基丁酸与卡泊芬净合用的FICI<0.5,说明氨基丁酸与卡泊芬净合用表现出协同关系。另外,在抗真菌试管敏感性实验中,1.25μmol·L-1的氨基丁酸联合0.012 5μg·mL-1的卡泊芬净与0.012 5μg·mL-1的卡泊芬净单用组相比,可以直观地观察到试管内浑浊程度明显减弱,SC5314的生长受到抑制。在生长曲线实验中,1.25μmol·L-1氨基丁酸联合0.012 5μg·mL-1卡泊芬净的生长曲线显著低于同浓度下两药单用的生长曲线(P<0.05)。结论氨基丁酸本身对白色假丝酵母菌标准株SC5314没有抑菌作用,但氨基丁酸能显著增强卡泊芬净对白色假丝酵母菌SC5314的杀菌作用。     

Candida spp. with acquired echinocandin resistance, France, 2004-2010

We report 20 episodes of infection caused by acquired echinocandin-resistant Candida spp. harboring diverse and new Fksp mutations. For 12 patients, initial isolates (low MIC, wild-type Fksp sequence) and subsequent isolates (after caspofungin treatment, high MIC, mutated Fksp) were genetically related.     

Emerging echinocandins for treatment of invasive fungal infections

The echinocandins are a new class of antifungals, developed in response to the need for safe and effective antifungals for the treatment of invasive fungal infections. These agents work by inhibiting 1,3-β-d-glucan synthase, an enzyme essential for production of cell walls in select fungi. Echinocandins appear to demonstrate favourable activity in vitro against a variety of yeasts (including both Candida albicans and non-albicans Candida) as well as select moulds (including Aspergillus spp.) In general, all echninocandins demonstrate a favourable safety profile and require once-daily parenteral administration. Caspofungin is the first of these agents to be available in the US, and is approved for empirical antifungal therapy in febrile neutropenic patients, candidaemia and select forms of invasive candidiasis, and for management of invasive aspergillosis in patients refractory to or intolerant of other therapies. Micafungin was recently approved by the FDA for treatment of oesophageal candidiasis, and for the prophylaxis of fungal infections in haematopoietic stem cell transplant recipients. Emerging data indicate micafungin may have an important role in the treatment of invasive forms of candidiasis. Anidulafungin is an echinocandin approved in the US for treatment of candidaemia and oesophageal candidiasis. Aminocandin (HMR-3702, IP-960) is an investigational agent, with published experience limited to in vitro studies and animal models of infection.     

The use of caspofungin in HIV-infected individuals

Fungal infections are a significant cause of HIV-related morbidity and mortality, particularly in the developing world, but also in countries with access to highly active antiretroviral therapy. New agents are essential to improve present efficacy rates, particularly in cases of drug resistance. Caspofungin is a new antifungal from the echinocandin class and is licensed for the treatment of candidal infections and as a second-line therapy for invasive aspergillosis. In this paper, the pharmacology, interaction and susceptibility data for this agent are reviewed and studies supporting the use of this agent in HIV-infected individuals are examined. Finally, evidence for the use of caspofungin for the treatment of Pneumocystis jiroveci pneumonia, an unlicensed indication, including a case series from our own unit is explored.     

Combination of caspofungin and low‐dose trimethoprim/sulfamethoxazole for the treatment of severe Pneumocystis jirovecii pneumonia in renal transplant recipients

Pneumocystis jirovecii pneumonia (PJP) is a severe and life‐threatening complication in immunocompromised patients. Trimethoprim/sulfamethoxazole (TMP‐SMZ) is well known for its effectiveness as prophylaxis of PJP. However, the use of TMP‐SMZ is associated with various adverse effects that may not be tolerated by critically ill patients. Caspofungin is recommended for invasive fungal infections, but the treatment of PJP after solid organ transplantation (SOT) is an off‐label use of this drug. In this study, three cases of severe PJP in renal transplant recipients treated with a combination of caspofungin and low‐dose TMP‐SMZ were presented. Initial findings indicated that the combined treatment may be beneficial for the treatment of PJP and decrease the incidence of TMP‐SMZ‐related adverse effects.     

LC-MS/MS法测定重症患者血浆中卡泊芬净的浓度

目的：建立LC-MS/MS法测定人血浆中卡泊芬净的浓度。方法：采用安捷伦ZORBAX Eclipse Plus C₁₈色谱柱（2.1 mm×100 mm, 3.5 μm）,柱温25℃,流动相为含0.1%甲酸的水和含0.1%甲酸的乙腈溶液,梯度洗脱,流速为0.3 mL·min^-1,分析时长8 min。采用电喷雾离子化,正离子模式多反应监测扫描分析,用于定量分析的离子对分别为：m/z 547.600→137.200（卡泊芬净）,m/z 749.800→591.400（内标阿奇霉素）。结果：卡泊芬净在0.06~14.27 μg·mL^-1范围内线性关系良好,定量下限为0.06 μg·mL^-1,准确度在±15%之间,日内及日间精密度RSD均小于10%,提取回收率为96.6%~102.0%。样本在室温放置4 h、4℃放置24 h、反复冻融3次、冰冻放置5 d和处理后自动进样器（4℃）放置8 h等条件下均稳定,RSD ≤ 7.1%。结论：本方法简便、快捷、灵敏、准确,适合临床上对卡泊芬净血药浓度的监测以及后续的药动学研究。     

卡泊芬净治疗55例恶性血液病患者侵袭性真菌感染的安全性研究

目的:评价卡泊芬净治疗血液病患者侵袭性真菌感染的疗效及安全性。方法:采用回顾性分析法统计本院2005年8月—2006年9月住院患者使用卡泊芬净的疗效和不良事件。结果:55例病历分析中显示卡泊芬净总有效率为57.1%,药物相关的不良反应发生率低且较轻。结论:卡泊芬净抗菌谱广,疗效确切,安全性好,是血液病患者抗真菌经验治疗的较为理想药物。