米卡芬净与伏立康唑联合治疗侵袭性真菌感染的临床研究

目的评价米卡芬净静脉注射后口服伏立康唑治疗ICU侵袭性真菌感染（IFI）疗效及安全性。方法将侵袭性真菌感染患者,根据不同抗真菌治疗方法分成两组,A组（16例）采用米卡芬净静注后伏立康唑口服联合疗法;B组（16例）,米卡芬净组静脉滴注米卡芬净（100mg／d）,观察两组患者的疗效和不良反应。结果A组的总有效率为87．5％（14／16）,药物相关的不良反应发生率6．3％（1／16）;B组的总有效率56．3％（9／16）,药物相关的不良反应发生率为25％（4／16）。两组总有效率较高,但有显著性差异（P〈0．05）,A组不良反应率显著低于B组。结论两种方案对侵袭性真菌感染的患者均有效,米卡芬净联合伏立康唑疗法比单独应用米卡芬净更具有疗效优势,且安全性好,不良反应少,有显著性差异（P〈0．05）。     

米卡芬净与伏立康唑联合治疗侵袭性真菌感染的临床研究

目的评价米卡芬净静脉注射后口服伏立康唑治疗ICU侵袭性真菌感染(IFI)疗效及安全性。方法将侵袭性真菌感染患者,根据不同抗真菌治疗方法分成两组,A组(16例)采用米卡芬净静注后伏立康唑口服联合疗法;B组(16例),米卡芬净组静脉滴注米卡芬净(100 mg/d),观察两组患者的疗效和不良反应。结果 A组的总有效率为87.5%(14/16),药物相关的不良反应发生率6.3%(1/16);B组的总有效率56.3%(9/16),药物相关的不良反应发生率为25%(4/16)。两组总有效率较高,但有显著性差异(P0.05),A组不良反应率显著低于B组。结论两种方案对侵袭性真菌感染的患者均有效,米卡芬净联合伏立康唑疗法比单独应用米卡芬净更具有疗效优势,且安全性好,不良反应少,有显著性差异(P0.05)。     

卡泊芬净治疗重症监护病房侵袭性真菌感染13例临床分析

目的探讨卡泊芬净治疗ICU侵袭性真菌感染(IFI)的疗效与安全性。方法回顾分析我院呼吸、急诊和外科ICU接受过卡泊芬净治疗的IFI患者临床资料。结果2005年5月—2006年11月共有13例接受了卡泊芬净治疗。13例中确诊IFI6例,包括念珠菌菌血症4例(白念珠菌2例,光滑念珠菌和近平滑念珠各1例)、肺IFI2例(光滑念珠菌和曲霉各1例);拟诊肺IFI3例(白念珠菌1例,曲霉2例);疑似肺IFI4例,病原真菌不明。基础疾病为心血管外科术后8例,骨科与普外科术后各1例,肺癌术后复发化疗、间质性肺疾病和成人Still′s病各1例。卡泊芬净中位疗程14(1~55d)d。1例于用药当天死于心脏骤停疗效无法判断,12例可评估患者中,痊愈4例(4/12,33.3%),显效4例(4/12,33.3%),总有效率(8/12,66.7%),进步和无效各2例。死亡6例(6/13,病死率46.2%)。治疗过程中未发现与卡泊芬净有关的不良反应。结论卡泊芬净是治疗IFI有效、安全的药物,值得进一步临床验证。     

米卡芬净在儿童恶性血液病患者合并肺部真菌感染中的临床应用

目的 探讨米卡芬净治疗儿童恶性血液病并侵袭性肺部真菌感染的疗效及安全性.方法 选取柘城县人民医院血液/肿瘤病区治疗恶性血液病合并肺部真菌感染患儿51例,随机分为两组,分别给予米卡芬净与伏立康唑治疗,比较两组的治疗有效率、痊愈率和不良反应发生率.结果 两组患儿在有效率和痊愈率方面比较差异无统计学意义（P〉0.05）,但在不良反应发生率方面,米卡芬净组患儿低于伏立康唑组患儿,差异有统计学意义（P〈0.05）.结论 米卡芬净与伏立康唑对儿童恶性血液病侵袭性肺部真菌感染均具有良好的疗效,但米卡芬净具有更好的安全性.     

卡泊芬净与氟康唑治疗慢阻肺急性加重期合并肺部真菌感染疗效对比

目的：分析卡泊芬净与氟康唑治疗慢阻肺（COPD）急性加重期合并肺部真菌感染的临床疗效。方法：选取2018年2月~2020年4月收治的COPD急性加重期合并肺部真菌感染患者60例,采用随机数字表法分为卡泊芬净组和氟康唑组,各30例。在常规治疗基础上,卡泊芬净组采用注射用醋酸卡泊芬净治疗,氟康唑组采用氟康唑注射液治疗,两组连续治疗2周。比较两组患者体温恢复正常时间、肺部真菌涂片检查转阴时间、白细胞恢复正常时间、真菌清除率以及不良反应发生情况。结果：卡泊芬净组患者体温恢复正常时间、肺部真菌涂片检查转阴时间以及白细胞恢复正常时间均短于氟康唑组,差异有统计学意义（P＜0.05）;治疗2周后,卡泊芬净组光滑念珠菌清除率及总清除率高于氟康唑组,差异有统计学意义（P＜0.05）。治疗期间,两组均未发生明显不良反应。结论：卡泊芬净治疗COPD急性加重期合并肺部真菌感染患者疗效要优于氟康唑,可以加速肺部真菌转阴和白细胞恢复正常,能更有效地清除真菌,且不良反应少,耐受性较好。     

卡泊芬净治疗儿童血液病侵袭性真菌感染的疗效及安全性评价

目的探讨卡泊芬净治疗儿童血液病侵袭性真菌感染的临床疗效及安全性。方法回顾性分析35例真菌感染的血液病患儿,给予静脉滴注卡泊芬净,第1天单次70mg/m2负荷剂量(日实际剂量不超过70mg),之后给予每天50mg/m2(日实际剂量不超过70mg),疗程4～36d,根据患儿临床表现和肺影像学变化判断疗效。结果确诊3例为血源感染,临床诊断25例、拟诊7例均为肺部感染,治疗总有效率71.43%;有效组疗程为(17.80±6.97)d,无效组疗程(10.40±5.54)d,差异有统计学意义(P<0.05);抢先/经验治疗组有效率为84%,高于目标/挽救治疗组的40%,差异有统计学意义(P<0.05);未见明显不良反应。粒细胞缺乏≥10d是治疗失败的危险因素。结论卡泊芬净治疗儿童血液病侵袭性真菌感染是安全有效的治疗选择;抢先治疗能提高疗效。     

卡泊芬净治疗恶性血液病化疗后中性粒细胞缺乏合并深部真菌感染的临床观察

目的分析卡泊芬净治疗恶性血液病化疗后中性粒细胞缺乏合并深部真菌感染临床效果及安全性。方法选取2009年3月至2012年5月收治恶性血液病化疗后中性粒细胞缺乏合并深部真菌感染患者50例,采用随机数字表法分为两性霉素B组和卡泊芬净组,分别采用两性霉素B和卡泊芬净静脉滴注治疗;比较两组患者临床治疗总有效率及不良反应发生率等。结果两性霉素B组总有效率(72.0%)与卡泊芬净组患者(76.0%)比较无显著差异(P>0.05);两性霉素B组不良反应发生率(36.0%)明显高于卡泊芬净组(P<0.05)。结论卡泊芬净早期治疗恶性血液病化疗后中性粒细胞缺乏合并深部真菌感染临床效果满意,且无严重不良反应。     

棘白菌素类的新品种:米卡芬净

米卡芬净[1]于2005年通过美国FDA的审批,成为继卡泊芬净之后第2个应用于临床的棘白菌素类药物。一、体外抗菌作用米卡芬净是水溶性抗真菌药,它主要抑制真菌细胞壁的主要成分1,3-β-D-葡聚糖合成,从而破坏真菌细胞壁的合成,影响细胞形态和渗透压,导致细胞溶解死亡。米卡芬净还能     

回顾卡芬净治疗高龄肺部真菌感染的疗效分析

目的：探讨卡泊芬净治疗高龄侵袭性肺部真菌感染患者的疗效和安全性。方法入选北京友谊医院医疗保健中心2010年12月至2012年7月接受过卡泊芬净治疗的侵袭性肺部真菌感染患者32例,对临床资料进行分析。根据诊断分为临床诊断病例（n=19）、拟诊病例（n=13）。根据侵袭性真菌感染的疗效评价标准,判定卡泊芬净对高龄侵袭性肺部真菌感染患者的有效率。同时观察该药的安全性。结果共入选32例80岁以上高龄患者。治疗的总有效率为71.9%。其中,痊愈15例（46.9%）,显效8例（25%）,进步5例（15.6%）,无效4例（12.5%）。治疗过程中2例患者出现谷丙转氨酶升高,考虑为与用药有关的肝功能受损所致。结论卡泊芬净对于治疗高龄患者侵袭性真菌感染安全有效。     

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。     

米卡芬净在造血干细胞移植二级预防中的临床应用分析

目的 探讨米卡芬净在有侵袭性真菌感染(invasive fungal infection,IFI)病史的患者行造血干细胞移植(haematopoietic stem cell transplantation,HSCT)时二级预防(secondary anti-fungal prophylaxis,SAP)的有效性和安全...     

Impact of special patient populations on the pharmacokinetics of echinocandins

Echinocandins belong to the class of antifungal agents. Currently, three echinocandin drugs are licensed for intravenous treatment of invasive fungal infections: anidulafungin, caspofungin and micafungin. While their antifungal activity overlaps, there are substantial differences in pharmacokinetics (PK). Numerous factors may account for variability in PK of echinocandins including age (pediatrics vs adults), body surface area and body composition (normal weight vs obesity), disease status (e.g., critically ill and burn patients) and organ dysfunction (kidney and liver impairment). Subsequent effects of altered exposure might impact efficacy and safety. Knowledge of PK behavior is crucial in optimal clinical utilization of echinocandin in a specific patient or patient population. This review provides up-to-date information on PK data of anidulafungin, caspofungin and micafungin in special patient populations. Patient populations addressed are neonates, children and adolescents, obese patients, patients with hepatic or renal impairment, critically ill patients (including burn patients) and patients with hematological diseases.     

Posaconazole: a new antifungal weapon

The last twenty years, the incidence of invasive fungal infections (IFI) has risen dramatically due to the prolongation of survival of patients with multiple risk factors for fungal infections. Amphotericin B was for more than 40 years the gold standard for almost all IFI, but toxicity and resistance, especially of new and emerging pathogens remained important issues. Fluconazole and itraconazole have also the same disadvantage of resistance. Voriconazole, a new triazole antifungal has offered an additional option, but the problem of resistant aspergillosis, and zygomycosis remains. Echinocandins (caspofungin, micafungin and anidulafungin) are active only against Candida and Aspergillus spp., but not against Fusarium, Scedosporium and Zygomycetes. Posaconazole is the most recently approved triazole with broad spectrum activity against Candida spp., Aspergillus spp., Cryptococcus neoformans, Zygomycetes, dermatiaceous, dimorphic, and other fungal pathogens. Interestingly, posaconazole is active against Candida spp., resistant to fluconazole and itraconazole, and Aspergillus fumigatus resistant to fluconazole itraconazole, amphotericin B, and voriconazole. The results from clinical trials of posaconazole as salvage treatment are encouraging. Multicenter clinical trials have also established its role in the prophylaxis of (IFI) in the severely immunocompromised patients such as those after hematopoietic stem cell transplantation (HSCT) who developed graft versus host disease (GVHD), as well as the neutropenic patients with an acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after myeloablative chemotherapy. Posaconazole has pharmacokinetic advantages and low side effect profile, which are very important, especially in the seriously ill population.     

国产两性霉素B治疗侵袭性真菌感染121例临床分析

目的 观察静脉用国产两性霉素B对血液病患者侵袭性真菌感染(IFI)的临床疗效及其安全性.方法 选择121例血液病患者静脉使用两性霉素B,剂量为5～50 mg/d,用药时间5～101d,中位数为19 d,并对用药前后患者肝、肾功能及电解质进行监测.结果 静脉使用两性霉素B临床总有效率为67.3%,真菌清除率为66.7%.不良反应包括寒战、高热、低钾血症、肝肾功能损害、胃肠道反应、静脉炎和皮疹.结论 只要合理应用,对其不良反应进行积极防治,两性霉素B仍是较为安全有效的一线抗真菌药物.     

Comparison of Efficacy and Safety of Caspofungin Versus Micafungin in Pediatric Allogeneic Stem Cell Transplant Recipients: A Retrospective Analysis

Introduction

The high morbidity and mortality associated with invasive fungal infections (IFIs) provide the rationale for antifungal prophylaxis in immuno-compromised pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Caspofungin and micafungin are antifungal agents of interest for prophylaxis of IFIs because of their potency against Candida and minimal toxicity or interactions with other drugs. Few studies have demonstrated the safety and efficacy of such echinocandins as prophylaxis for IFIs in patients undergoing HSCT.

Methods

This retrospective cohort study compared caspofungin and micafungin for prevention of IFIs in 93 pediatric patients undergoing HSCT for oncological or non-oncological disease. The observation began with the first dose of antifungal agent and ended 3 months after transplantation.

Results

Patients in the micafungin group had a higher overall treatment success rate of 87.2 versus 84.8% in the caspofungin group, but the difference was not significant. There were no statistically significant differences in the incidence or type of proven/probable IFIs between the 2 groups. The low incidence of death did not differ statistically between the groups. Patients in the caspofungin group presented more frequently with fever, during and after neutropenia. In both groups, we observed an expected worsening of blood chemistry parameters. There were no adverse events definitely attributable to the two antifungal agents.

Conclusion

These results demonstrate good efficacy and tolerability for caspofungin and micafungin. However, better results with respect to the incidence and resolution of fever in the micafungin group may suggest its use in preference to that of caspofungin.

     

Overexpression of Candida albicans CDR1, CDR2, or MDR1 does not produce significant changes in echinocandin susceptibility

The micafungin and caspofungin susceptibilities of Candida albicans laboratory and clinical isolates and of Saccharomyces cerevisiae strains stably hyperexpressing fungal ATP-binding cassette (ABC) or major facilitator superfamily (MFS) transporters involved in azole resistance were determined using three separate methods. Yeast strains hyperexpressing individual alleles of ABC transporters or an MFS transporter from C. albicans gave the expected resistance profiles for the azoles fluconazole, itraconazole, and voriconazole. The strains hyperexpressing CDR2 showed slightly decreased susceptibility to caspofungin in agar plate drug resistance assays, as previously reported, but increased susceptibility to micafungin compared with either the strains hyperexpressing CDR1 or the null parent deleted of seven ABC transporters. The strains hyperexpressing CDR1 showed slightly decreased susceptibility to micafungin in these assays. A C. albicans clinical isolate overexpressing both Cdr1p and Cdr2p relative to its azole-sensitive isogenic progenitor acquired resistance to azole drugs and showed reduced susceptibility to caspofungin and slightly increased susceptibility to micafungin in agar plate drug resistance assays. None of the strains showed significant resistance to micafungin or caspofungin in liquid microdilution susceptibility assays. The antifungal activities of micafungin and caspofungin were similar in agarose diffusion assays, although the shape and size of the caspofungin inhibitory zones were affected by medium composition. The assessment of micafungin and caspofungin potency is therefore assay dependent; the differences seen with agar plate drug resistance assays occur over narrow ranges of echinocandin concentrations and are not of clinical significance.     

Echinocandins in invasive candidiasis]

Invasive fungal infections on the intensive care unit are predominantly caused by Candida spp., most frequently manifesting as candidemia. In spite of increasing treatment options during the last 2 decades, mortality of invasive candidiasis remains high with 20-50%. With the echinocandins, a new class of antifungal drugs with activity against clinically relevant Aspergillus and Candida spp. has become available since the beginning of the new millennium. The echinocandins have shown convincing efficacy in numerous multicenter, mostly double-blinded phase III clinical trials. These trials compared current standard treatment regimens with the echinocandins anidulafungin, caspofungin, and micafungin. All trials observed noninferiority of the new drugs against the standard treatment; in the case of anidulafungin, superiority against fluconazole was demonstrated. Especially in trials utilizing amphotericin B as comparator, significantly less treatment-related adverse events were observed when using an echinocandin. Echinocandins have a low drug-drug interaction profile and are only marginally affected by liver function. Especially in ICU (intensive care unit) patients frequently showing single- or multiorgan failure and receiving a multitude of drugs with complex interactions, echinocandins have become the treatment of first choice for invasive candidiasis.     

Differences in efficacy and cytokine profiles following echinocandin or liposomal amphotericin B monotherapy or combination therapy for murine pulmonary or systemic Aspergillus flavus infections

Given the recent increase in aspergillosis caused by species other than Aspergillus fumigatus, micafungin, caspofungin, and liposomal amphotericin B (L-AmBi) were investigated as monotherapy or combination therapy for murine systemic or pulmonary Aspergillus flavus infection. Treatment for 3 or 6 days was begun at 24 h (intravenous [i.v.], 2.8 × 10(4) conidia) or 2 h (intranasal, 4.1 × 10(6) to 6.75 × 10(6) conidia) postchallenge as follows: 5 or 10 mg/kg L-AmBi, 10 mg/kg caspofungin, 15 mg/kg micafungin, L-AmBi plus echinocandin, L-AmBi on days 1 to 3 and echinocandin on days 4 to 6, or echinocandin on days 1 to 3 and L-AmBi on days 4 to 6. Mice were monitored for survival, fungal burden, serum or tissue cytokines, and lung histopathology. In the systemic infection, micafungin or caspofungin was more effective than L-AmBi in prolonging survival (P < 0.05), and L-AmBi was associated with significantly elevated serum levels of interleukin-6 (IL-6), macrophage inflammatory protein 1α (MIP-1α), and IL-12 (P < 0.05). In contrast, L-AmBi was significantly more effective than the echinocandins in reducing fungal growth in most tissues (P < 0.05). Concomitant therapies produced significantly enhanced survival, reduction in fungal burden, and low levels of proinflammatory cytokines, while antagonism was seen with some sequential regimens. In comparison, in the pulmonary infection, L-AmBi was significantly better (P < 0.05) than caspofungin or the combination of L-AmBi and caspofungin in prolonging survival and reducing lung fungal burden. Caspofungin stimulated high lung levels of IL-1α, tumor necrosis factor alpha (TNF-α), and IL-6, with extensive tissue damage. In summary, systemic A flavus infection was treated effectively with L-AmBi plus micafungin or caspofungin provided that the drugs were administered concomitantly and not sequentially, while pulmonary A. flavus infection responded well to L-AmBi but not to caspofungin.