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。     

米卡芬净抗侵袭性真菌感染的临床观察

侵袭性真菌感染发生率日益增加,病情进展迅速、凶险,已成为导致危重病患者死亡的主要原因之一[1-3].临床工作中,除了采取积极的预防措施外,早期诊断真菌感染并采取安全有效的抗真菌药物是危重病患者救治成功的关键.     

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.     

卡泊芬净治疗侵袭性真菌病的临床研究

目的 探讨卡泊芬净治疗侵袭性真菌病(IFD)的疗效与安全性.方法 回顾分析北京安贞医院呼吸科、急诊科和外科ICU接受卡泊芬净治疗的IFD患者临床资料.结果 2005年5月-2009年12月共35例接受卡泊芬净治疗患者.其中,确诊20例,包括念珠菌血症18例(白念珠菌10例,近平滑念珠菌3例,光滑念珠菌和热带念珠菌各2...     

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)。     

卡泊芬净治疗肾移植后肺部侵袭性真菌感染：12例分析

背景：肾移植后侵袭性真菌感染是肾移植失败的主要原因。卡泊芬净具有独特的抗真菌机制,对氟康唑和伊曲康唑耐药的念珠菌有很强的抗菌作用,并表现出很好的耐受性,且没有与剂量或作用持续时间相关的毒性。 目的：评价卡泊芬净治疗肾移植后肺部侵袭性真菌感染的有效性和安全性。 方法：回顾性分析2013年1至12月三门峡市中心医院呼吸科诊断为肺部侵袭性真菌感染的肾移植患者,采用卡泊芬净抗真菌治疗,卡泊芬净首剂为70 mg/d,继以50 mg/d,静脉滴注。用药后每周最少监测2次肝功能,若肝功能损害加重或出现新的肝功能损害,根据肝脏功能调整剂量或者停药,疗程为10-14 d。观察患者的疗效和不良反应。 结果与结论：共收治12例患者,可以找到真菌微生物学证据者占67%,其培养真菌以念珠菌为主,占75%,合并细菌感染比例为58%,合并巨细胞病毒感染的比例为25%。治疗有效率为92%（11/12）,死亡率为8%（1/12）,不良事件发生率为25%。提示对于肾移植后侵袭性真菌感染患者的经验性抗真菌治疗,卡泊芬净的疗效较好,且不良事件发生率低。卡泊芬净可以作为肾移植后侵袭性真菌感染的首选药物。     

卡泊芬净治疗危重患者肺部真菌感染的护理

危重患者由于严重的基础疾病、合并疾病、手术、导管留置以及广谱抗菌药、糖皮质激素的应用等,使肺部真菌感染患病率增加。卡泊芬净具有广谱抗真菌作用,对白色念珠菌、非白色念珠菌及曲霉菌均具有很好的抗菌活性,     

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。     

Nationwide survey of treatment for pediatric patients with invasive fungal infections in Japan

In Japan, only a few antifungal agents have been approved for children, but in actual clinical practice, various antifungal agents used in adults are administered to pediatric patients with invasive fungal infections (IFIs). However, the pediatric dosages of some antifungal agents are not indicated in the package inserts or mentioned in the Japanese Mycology Study Group 2007 Guidelines for Management of Deep-seated Mycoses. We conducted a nationwide survey to determine how antifungal agents are being used to treat pediatric patients with IFIs in Japan. We sent a questionnaire to 792 medical centers that train pediatricians and received 250 (31.6 %) responses. In the past 5 years, 65 (26.0 %) of 250 facilities reported treating a total of 232 cases of IFIs. The characteristics of pediatric patients with IFIs were almost the same as adult patients except that immunological diseases and neonatal diseases are common as underlying diseases. Antifungal agents used in adults were all used in children. However, the dosages of some antifungal agents deviated from the package insert or guideline recommendations. As for the reasons for selecting a particular antifungal agent, strong antifungal activity (including potency, broad spectrum, and clinical efficacy) was favored over safety. These results can be used to revise guidelines for the management of children with IFIs.     

Current challenges in the management of invasive fungal infections

The incidence of invasive fungal infections (IFIs) has increased over the past two decades, as the populations of patients at risk have continued to rise. Early and accurate diagnosis and the subsequent usage of appropriate antifungal therapy are difficult, which leads to a high mortality rate in patients with IFI. Along with the widespread use of antifungal prophylaxis, the epidemiology of invasive fungal pathogens has changed. Non-albicans Candida, Non-fumigatus Aspergillus, and molds other than Aspergillus have become more common pathogens causing invasive diseases, and most of these emerging fungi are resistant to or less susceptible than others to standard antifungal agents. Therefore, invasive infections due to these previously rare fungi are more difficult to treat. Advances in more potent and less toxic antifungal agents, such as second-generation triazoles and echinocandins, may potentially improve the outcomes of these infections. Recent advances in detecting fungal cell-wall components and genomic DNA also allow earlier diagnosis. This article reviews the changing spectrum of invasive fungal infections and the introduction of recent advances in diagnostic tools and antifungal agents.     

Distribution of micafungin in the tissue fluids of patients with invasive fungal infections

The distribution of micafungin (MCFG) in tissue fluids, such as cerebrospinal fluid (CSF), pleural effusions, ascites, and wound tissue fluids, was examined in seven patients with invasive fungal infections. MCFG (100–300 mg) was administered once daily over a 1-h intravenous infusion. Blood and tissue fluid samples were collected from 1 to 24 h after infusion. Although two patients had similar MCFG concentrations in their plasma, the concentrations in the CSF differed between these two patients. The concentration in the CSF of one patient was much higher than the MIC₉₀ for Candida albicans, Candida glabrata, and Aspergillus fumigatus, whereas the MCFG concentration in the CSF of the other patient was comparable to the MIC₉₀. By contrast, MCFG concentrations in pleural effusions, ascites, and wound tissue fluids were above the MIC₉₀ . These results suggest that intravenous MCFG may be effective to treat invasive fungal infections that invade the organs and tissues.     

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.     

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.     

Invasive fungal infections in pediatric patients: a review focusing on antifungal therapy

Invasive fungal infections in children appear to have increased over the past few decades. Substantial differences compared with adult patients in risk factors, pathogen epidemiology, pathophysiology and, most notably, pharmacokinetics of antifungal agents require age-adapted management and treatment approaches. The present article reviews these aspects for invasive aspergillosis and invasive candidiasis, the two most common life-threatening fungal infections.     

血液疾病患者并发侵袭性真菌感染的危险因素及预后分析

目的 分析血液系统疾病患者侵袭性真菌感染(IFI)的发生率、危险因素、预后和高危人群.方法 回顾性分析2007年1月1日至2008年12月31日在我院移植中心住院时间≥2周的病例.应用逻辑回归、递归分割等方法分析IFI的危险因素和高危人群,IFI发生率的估计应用累积发生率,预后分析应用Kaplan-Meier生存分析....     

恶性血液病患者侵袭性真菌感染GM和BG抗原检测的价值

目的 评价半乳甘露聚糖(GM)抗原和(1→3)-β-D葡聚糖(BG)抗原检测对恶性血液病患者侵袭性真菌感染(IFI)的诊断价值以及两种方法在监测抗真菌治疗效果中的作用.方法 51例恶性血液病患者当体温超过38 ℃,持续48 h以上,经广谱抗生素治疗无效,或起初有效但体温下降后再次升高时被纳入本研究.第1周采集患者静脉血2次,以后每周采血1次,至少监测4周.分别采用ELISA法和比色法检测患者血清GM和BG值.GM实验阳性定义为连续两次不同时点检测GM值＞0.5或单次＞0.8,G实验阳性定义为BG值＞80 pg/ml.患者分为确诊、临床诊断、拟诊及非真菌感染四组,21名正常志愿者作为对照.结果 51例患者共收集240份血清标本.其中确诊IFI2例,临床诊断26例,拟诊17例,非真菌感染6例.以确诊及临床诊断为真阳性组,以非真菌感染为真阴性组.GM实验在真阳性组28例中21例阳性,真阴性组6例中1例阳性,敏感性75%,特异性83.3%,阳性预测值95.5%,阴性预测值41.7%;G实验在真阳性组28例中全部阳性,真阴性组6例中4例阳性,敏感性100%,特异性33.3%,阳性预测值87.5%,阴性预测值100%.G实验的敏感性高于GM实验,差异有统计学意义(P=0.015);但特异性差异无统计学意义(P=0.242).GM实验阳性的21例患者中抗真菌治疗有效19例,GM值渐转阴性,2例无效的患者GM值持续阳性,有效组GM平均值两周后明显低于无效组,差异有统计学意义(P＜0.05);G实验阳性的患者中治疗有效者BG值逐渐下降,但未转阴;治疗无效组BG值变化无规律,总体呈上升趋势,但各时间点BG值监测对疗效无明显判断意义.结论 血清GM和BG抗原检测可以为早期诊断IFI提供有力证据,联合检测BG和GM两种抗原,可提高对曲霉菌诊断的特异性,减少假阳性.治疗中监测GM和BG值的动态变化,GM实验用于评价疗效的价值优于G实验.

Abstract：

Objective To evaluate the diagnostic value of serum galactomannan antigen (GM)and (1→3)-β-D-glucan antigen(BG) assay in invasive fungal infections( IFI ) in the patients with hematologic malignancies and the role in monitoring therapeutic response. Methods Fifty one patients with hematological malignancies met the criteria for inclusion: ①body temperature above 38 ℃ for 48 hours, ②failure to respond to broad-spectrum antibiotic treatment, or ③temperature rose again after the responded drop. Blood samples were collected twice at the first week, then once a week in at least four weeks. The double antibody sandwich enzyme-linked immunosorbent assay( EL1SA )and colorimetric assay were used for detecting GM and BG. The positive GM test is defined as two consecutive tests at different time GM value ＞ 0.5 or ＞ 0. 8 and the positive G test is defined as BG value ＞ 80 pg/ml. The patients were assigned into four groups as proven,probable, possible, and non-fungal infection respectively, and 21 normal volunteers were as controls. Results Two hundred and forty serum samples were collected from 51 patients including 2 of proven IFI, 26 probable IFI, 17 possible IFI and 6 non-fungal infection. The true-positive group including the proven and probable groups, and true negative group was the non-fungal infection group. GM tests were positive in 21 of 28 cases in true positive group, and only one of 6 cases in non-fungal infection. The sensitivity, specificity,positive predictive value and negative predictive value were 75%, 83.3%, 95.5% and 41.7%, respectively. G tests were positive in all 28 cases of the true positive group, and 4 in 6 non-fungal infection cases. The sensitivity, specificity, positive predictive value and negative predictive value were 100%, 33.3%, 87.5% and 100%, respectively. G test is more sensitive than GM test ( P = 0.015 ), but there was no significant difference in specificity of the two tests (P =0.242). In 19 of 21 patients with GM test positive, anti-fungal treatment was effective, and GM value gradually decreased to negative, two invalid patients were persistent with GM test positive. After two weeks treatment, the average GM value was significantly lower in the effective group than in the ineffective group (P ＜ 0.05 ). BG values in the responded patients showed a gradual decline similar to that of GM values, but not to negative. The changes of BG value in ineffective group varied with a trend upward. The changes in BG value had no relation with treatment effectiveness. Conclusions Serum GM and BG antigens detection provides strong evidence for early diagnosis of IFI. Combination of GM and G tests can improve the diagnostic specificity and reduce the false positive GM test seems superior to G test for monitoring GM and BG values during treatment.