卡泊芬净治疗心脏术后侵袭性真菌病20例临床分析

目的:探讨卡泊芬净治疗心脏术后并发侵袭性真菌感染(IFI)的疗效与安全性。方法:回顾分析我院呼吸科、心外科和急诊重症监护室(ICU),接受过卡泊芬净治疗的心脏术后合并IFI患者临床资料。结果:2005年5月至2010年12月,共有20例接受了卡泊芬净治疗。男性12例,女性8例,中位年龄65岁(23～82)岁。确诊10例,皆为念珠菌血症(白念珠菌4例,近平滑念珠菌3例,光滑念珠菌、热带念珠菌和克柔念珠菌各1例);临床诊断肺IFI 5例(念珠菌3例,曲霉2例);拟诊肺IFI 5例,病原真菌不明。冠状动脉搭桥(CABG)术8例,瓣膜手术8例,胸主动脉瘤手术2例,先天性心脏病(先心病)和马方综合征手术各1例。卡泊芬净的使用时间中位数为18(1～55)d。1例于用药当天死于心脏骤停疗效无法判断,19例可评估患者中,痊愈10例(10/19,52.6%),显效4例(4/19,21.1%),总有效率为73.7%,进步3例,无效2例。死亡6例(6/20,病死率30.0%)。治疗过程中未发现与卡泊芬净有关的不良反应。结论:卡泊芬净是治疗心脏术后并发IFI的有效安全药物,值得进一步临床验证。     

卡泊芬净治疗危重病难治性侵袭性真菌感染临床研究

目的 评价卡泊芬净治疗氟康唑治疗无效的危重病侵袭性真菌感染患者的疗效和安全性.方法 采用开放性临床研究,对2005年5月至2007年6月浙江省人民医院ICU住院患者氟康唑治疗无效的44例侵袭性真菌感染患者,给予卡泊芬净首日负荷剂量70 mg,之后以50 mg/d维持治疗,疗程为10～40 d.结果 42例可评价患者中,痊愈18例(42.86%),显效14例(33.33%),总有效率76.19%,真菌清除率为62.22%.不良反应少,所有患者均耐受治疗.结论 卡泊芬净治疗危重病患者难治性侵袭性真菌感染安全、有效.     

卡泊芬净治疗侵袭性真菌感染疗效观察

目的探讨卡泊芬净治疗侵袭性真菌感染（IFI）的疗效与安全性。方法对20例外科ICU IFI患者使用卡泊芬净50mg／d,观察临床疗效与不良反应。结果IFI痊愈8例,显效6例,进步4例,无效2例,有效率为70％,未出现严重不良反应。结论卡泊芬净治疗IFI患者疗效确切,不良反应小。     

卡泊芬净治疗恶性血液病合并侵袭性肺部真菌感染的临床疗效观察

目的 观察卡泊芬净在恶性血液病患者肺部真菌感染治疗中的疗效及安全性.方法 回顾性分析我科2007年10月～2014年1月间49例恶性血液病合并侵袭性肺部真菌感染患者的临床资料,评估其静脉应用卡泊芬净治疗的临床疗效,并于治疗期间监测肺部影像学、肝肾功能等.结果 49例患者中,临床诊断10例,拟诊39例;卡泊芬净治疗7 d ～ 210 d,总有效率为53.6％;临床诊断10例患者中,临床治愈0例,临床显效4例,进步2例,无效4例,有效率为40％;拟诊39例患者中,临床治愈8例,临床显效14例,进步8例,无效9例,有效率为56.4％;初始治疗组37例,有效率54.5％,挽救性治疗组12例,有效率50.0％;仅1例患者在治疗期间出现一过性谷丙转氨酶增高,至67 IU/L,其他患者用药过程中均未出现明显不良反应.结论 卡泊芬净治疗恶性血液病患者合并侵袭性肺部真菌感染患者具有一定疗效且安全性好.     

几种常用抗真菌药物在恶性血液病合并侵袭性真菌病中的疗效分析

目的探讨临床上常用抗真菌药物在恶性血液病合并侵袭性真菌病(IFD)患者中的总体疗效、分层诊断疗效、疗效与感染部位的关系以及常见毒副反应。方法回顾性分析2005年1月至2008年8月在中山大学附属第一医院住院的117例恶性血液病合并IFD患者的临床资料。结果伊曲康唑、伏立康唑、卡泊芬净和脂质体两性霉素B治疗的总有效率分别为69.0%(40/58)、77.4%(24/31)、64.7%(11/17)和63.6%(7/11)(P=0.726);肺部感染患者中,4种药物的有效率分别为63.0%(17/27)、85.7%(12/14)、50.0%(4/8)和62.5%(5/8)(P=0.283);在肝脾念珠菌病、真菌血症及不明部位感染患者中,各用药组患者疗效相似;6周时各组存活率分别为86.2%、87.1%、70.6%和72.7%。伊曲康唑和伏立康唑常见副反应主要为胃肠道反应和轻度低钾血症,前者副反应有胃肠道反应(12.1%)、低钾血症(20.7%),伏立康唑组个别患者出现视觉异常(9.7%)和椎体外系症状(6.4%);卡泊芬净毒副反应轻微,仅见胃肠道反应(15.4%);脂质体两性霉素B组毒副反应较常见,为寒战发热(81.8%)、低钾血症(100%)、胃肠道反应(18.2%)和肝损害(9.1%)。结论伊曲康唑、伏立康唑、卡泊芬净和脂质体两性霉素B在恶性血液病合并IFD中总体疗效、分层诊断疗效以及6周存活率相当,临床治疗可根据患者特点选择个性化用药方案。     

继发性肺部念珠菌感染47例治疗分析

目的 探讨继发性肺部念珠茵感染的诊断和治疗相关问题.方法 收集2004-09-01-2006-08-31广东省人民医院呼吸内科47例住院患者,其中男24例,女23例.年龄(57.0±16.1)岁.均有住院时间较长、发热、有肺部感染性病变、普通抗感染治疗无效、呼吸道分泌物找到念珠茵并经抗真茵治疗有效,对其临床诊治情况进行分析.体温平均(38.4±0.6)℃,发热时间均超过6 d.发现真茵时的住院天数为(17.7±5.2)d,全部病例均有基础疾病.结果 病例的病原体包括:白色念珠茵38株,光滑念珠菌5株,克柔念殊菌2株,热带念珠菌1株,葡萄牙念珠菌1株.使用氟康唑进行治疗的28例患者,1例白色念珠菌和1例光滑念珠菌治疗无效,改用伏立康唑后治疗成功.使用伊曲康唑进行治疗的9例患者,有1例白色念珠菌和1例光滑念珠菌治疗无效,改用伏立康唑后治疗有效.使用伏立康唑进行治疗的7例全部有效,包括3例光滑念珠茵、1例葡萄牙念珠菌和3例白色念珠菌.7例使用卡泊芬净进行治疗的全部有效,本研究该药物抗真茵治疗覆盖了3例光滑念珠菌、2例克柔念珠菌、1例热带念珠菌和1例白色念珠菌.结论 本组继发性肺部念珠菌感染以白色念珠菌为主,全部患者均有发热.目前使用的新一代抗真菌药物伏立康唑、卡泊芬净均有可靠的疗效,其中卡泊芬净具有更好的安全性和耐受性.     

卡泊芬净联合复方磺胺甲嗯唑治疗重症肺孢子菌肺炎

目的 探讨卡泊芬净联合复方磺胺甲嗯唑治疗重症肺孢子菌肺炎的疗效.方法 分析总结6例肺孢子菌肺炎患者的临床特点和诊治经过.结果 6例患者均接受卡泊芬净联合复方磺胺甲噁唑治疗,除1例放弃治疗外,其余5例均收到满意疗效.其中3例患者初始单用复方磺胺甲噁唑治疗,病情无好转,后改为联合卡泊芬净,病情得到控制.结论 卡泊芬净联合复方磺胺甲噁唑治疗肺孢子菌肺炎取得了满意疗效,值得推荐作为单用复方磺胺甲噁唑不能控制的肺孢子菌肺炎的治疗选择.     

卡泊芬净治疗白血病并发侵袭性肺部真菌感染4例的临床观察

卡泊芬净是一种新型葡聚糖合成酶抑制剂类抗真菌药,我院血液肿瘤病房自2004年11月～2006年4月对4例白血病并发侵袭性肺部真菌感染的患者使用卡泊芬净治疗,现报告治疗体会.     

泊沙康唑初级预防急性髓系白血病诱导化疗后发生侵袭性真菌病的临床评估

目的观察泊沙康唑口服悬液初级预防急性髓系白血病(AML)患者诱导化疗后发生侵袭性真菌病(IFD)的疗效及毒副反应。方法收集2016年5月至2018年5月宁波市鄞州人民医院血液科收治的所有符合入选和排除标准的初诊AML患者206例(除外急性早幼粒细胞白血病、入院后接受静脉抗真菌或诱导化疗前1个月发生IFD、合并重要脏器功能不全、年龄>65岁),其中诱导化疗期间使用泊沙康唑口服悬液进行初级预防IFD的患者47例(泊沙康唑组),使用伏立康唑片进行初级预防IFD的患者61例(伏立康唑组),未进行初级预防IFD的患者98例(对照组)。对各组临床资料进行回顾性分析,比较3组诱导化疗期间IFD的发生率及泊沙康唑口服悬液、伏立康唑片的药物安全性。结果(1)泊沙康唑组出现5例(10.6%)IFD,均为拟诊病例;伏立康唑组出现11例(18.0%)IFD,其中拟诊7例,临床诊断3例,确诊1例;对照组出现35例(35.7%)IFD,其中拟诊19例,临床诊断11例,确诊5例。泊沙康唑组和伏立康唑组IFD的发生率均明显低于对照组(P值均<0.05)。泊沙康唑组IFD的发生率低于伏立康唑组,但差异无统计学意义(P>0.05)。(2)泊沙康唑组不良事件发生率明显低于伏立康唑组[12.8%(6/47)比32.8%(20/61),P<0.05]。结论(1)AML诱导化疗期间使用泊沙康唑口服悬液或伏立康唑片进行初级预防,可以明显减少IFD的发生率;(2)AML诱导化疗期间使用泊沙康唑口服悬液和伏立康唑片进行初级预防IFD的疗效相当,但泊沙康唑口服悬液安全性更好。     

造血干细胞移植后侵袭性真菌病的临床研究

目的探讨造血干细胞移植(hematopoietic stem cell transplantation,HSCT)后侵袭性真菌病(invasive fungal disease,IFD)的发生率、发病时间、临床表现及治疗效果。方法对军事医学科学院附属医院造血干细胞移植科2000年1月至2006年12月326例行HSCT的病例进行回顾性分析。结果326例行HSCT的患者中39例发生了IFD,发生率为11.9%。确诊9例,临床诊断21例,拟诊9例。39例IFD中,念珠菌病7例,霉菌病32例。HLA相合同胞、无关相合或相关不合及自体HSCT的IFD发生率分别为11.1%(26/234),18.5%(10/54)和7.9%(3/38)。30例出现IFD患者有移植物抗宿主病(graft versus host disease,GVHD)。IFD发生的中位时间78(17~198)d,临床表现主要是发热,广谱抗生素治疗无效,部分患者出现低氧血症。39例中,存活21例,死亡18例,联合抗真菌药物治疗9例患者6例存活。结论IFD是HSCT后的主要死亡原因,无关供者和相关不合的HSCT的IFD发生率明显升高,有GVHD患者发生IFD机会明显增加,联合抗真菌治疗效果有待进一步证实。     

A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis

BACKGROUND: Candida esophagitis remains an important cause of morbidity in patients with advanced human immunodeficiency virus (HIV) infection. Fluconazole is widely regarded as the treatment of choice for this condition. METHODS: The efficacy and safety of caspofungin were compared with fluconazole in adult patients with Candida esophagitis in a double-blind randomized trial. Eligible patients had symptoms compatible with esophagitis, endoscopic demonstration of mucosal plaques, and microscopic demonstration of Candida from the esophageal lesions. Patients were randomly assigned to receive caspofungin (50 mg) or fluconazole (200 mg) intravenously once daily for 7 to 21 days. The primary endpoint was the combined response of symptom resolution and significant endoscopic improvement 5 to 7 days after discontinuation of treatment. Data were analyzed with a modified intention-to-treat analysis, which excluded 2 ineligible patients. RESULTS: Most patients (154/177; 87%) had HIV infection, with a median CD4 count of 30 cells/mm(3). Candida albicans was the predominant isolate. Favorable response rates were achieved in 66 (81%) of the 81 patients in the caspofungin arm and in 80 (85%) of the 94 patients in the fluconazole arm (difference = -4%; 95% confidence interval: -15% to +8%). Symptoms had resolved in >50% of patients in both groups by the fifth day of treatment. No patient in the caspofungin group developed a serious drug-related adverse event; therapy was only discontinued in 1 patient (receiving fluconazole) due to a drug-related adverse experience. Four weeks after stopping study drug, symptoms had recurred in 18 (28%) of 64 patients given caspofungin and in 12 (17%) of 72 patients given fluconazole (P = 0.19). CONCLUSIONS: In this study, caspofungin appeared to be as efficacious and generally as well tolerated as fluconazole in patients with advanced HIV infection and documented Candida esophagitis.     

慢性阻塞性肺病继发肺部真菌感染41例临床分析

目的探讨慢性阻塞性肺病(COPD)继发肺部真菌感染的常见原因及对策。方法对41例COPD伴真菌感染病例进行回顾性分析。结果应用抗生素3种以上者23例(56.10%),5种以上者10例(24.39%),29例同时使用了糖皮质激素(70.73%),痰培养的真菌谱为:白念珠菌24例(58.54%),热带念珠菌5例,克柔念珠菌2例,酵母样菌7例,曲霉菌3例。治愈26例(63.41%),好转6例(14.63%),无变化4例(9.76%),死亡5例,病死率12.19%。结论广谱抗生素和糖皮质激素的广泛应用是COPD继发肺部真菌感染的主要原因,及时诊断和治疗可提高其治愈率。     

Response and relapse rates of candidal esophagitis in HIV-infected patients treated with caspofungin

Caspofungin is a new antifungal drug of the echinocandin class. We analyzed the clinical efficacy of caspofungin (50 mg/day) in the treatment of HIV-infected adults with endoscopically documented Candida esophagitis and enrolled in four clinical trials of caspofungin. Symptoms were evaluated daily; a favorable outcome required complete resolution of all esophageal symptoms assessed at the time of discontinuation of therapy. Relapse was defined as recurrent symptoms during the subsequent 2 weeks. A multivariate logistic regression model was developed to identify potential factors (including severity of symptoms at presentation, CD4(+) cell count on entry, extent of disease [assessed endoscopically at baseline], causative Candida species, duration of therapy [overall and after resolution of symptoms], time on treatment before symptom resolution, and antifungal prophylaxis) that might predict symptomatic relapse in the 2 weeks following completion of therapy. The median CD4(+) lymphocyte count for the entire population was 31/mm(3). Candida albicans was isolated from 109 of 110 patient samples cultured for the pathogen and constituted the sole isolate in 77%. Extensive esophageal involvement was present in 55% of patients at the time of pretreatment endoscopy. The duration of therapy ranged from 7 to 20 days (median, 12 days). Symptoms resolved in 117 of 123 patients (95%; 95% confidence interval, 90-98%) with a median time of ~4 days. Response rates were 43 of 46 (93%) and 70 of 73 (96%) for patients with greater or fewer than 50 CD4(+) cells/mm(3), and 80 of 85 (94%) and 23 of 24 (96%) in infections caused by C. albicans alone or in association with non-albicans isolates, respectively. Symptoms recurred within 2 weeks of stopping caspofungin in 19 of 115 evaluable patients (17%), including 3 of 16 (19%) receiving antifungal prophylaxis. Relapse rates were similar for patients with greater or fewer than 50 CD4(+) cells/mm(3). In this relatively small number of patients, only symptom severity and extent of disease judged endoscopically at baseline were significantly (p < 0.10) associated with early relapse in the multivariate model.     

Candida albicans endocarditis treatment with caspofungin in an HIV-infected patient--case report and review of literature

Caspofungin has recently been introduced for the treatment of invasive candidiasis, however, there is limited data on its use in endocarditis. We report a 22-year-old male HIV-infected patient on methadone maintenance therapy that developed right-sided Candida albicans endocarditis. Caspofungin treatment and vegetectomy, followed by fluconazole, was successful in the treatment of our patient. We also review all previous cases of Candida endocarditis treated with caspofungin.     

Evaluation of caspofungin and amphotericin B deoxycholate against Candida albicans biofilms in an experimental intravascular catheter infection model

Candida albicans biofilms complicate the treatment of infected implanted intravascular devices because of decreased antifungal susceptibility. In our investigation, 48 rabbits with experimental central venous catheter C. albicans infection were equally allocated to a control arm or to receive amphotericin B deoxycholate or caspofungin treatment while undergoing systemic and intraluminal lock therapy for 7 days. C. albicans was cultured from catheters from all control rabbits, from 3 that received amphotericin B, and from 0 that received caspofungin. Differences in colony counts were detected between the control and amphotericin (P<.001) and control and caspofungin (P<.001) arms. Caspofungin may be useful in the treatment of C. albicans biofilm-associated intravascular catheter infections, which warrants further study.     

The role of fluconazole in the treatment of Candida endocarditis: a meta-analysis

The treatment of Candida infective endocarditis generally involves infected valve removal accompanied by antifungal therapy with amphotericin B or a lipid-based derivative, with or without flucytosine. While often used as chronic suppressive therapy in these patients, the precise role for fluconazole has not been established. We conducted a meta-analysis of 64 literature cases of Candida endocarditis whose management did not include valve replacement but who received fluconazole, alone or concurrently or in sequence with 1 or more other antifungal drugs.Forty-nine (77%) patients were cured (n = 44) or improved (n = 5), 4 relapsed (6%), and 11 failed (10 of whom died) (17%). Among 19 patients for whom fluconazole was administered as the sole antifungal therapy, 11 (58%) were cured or improved. In contrast, among 45 patients who received 1 or more other antifungal agents in addition to fluconazole, 38 (84%) were cured or improved (p = 0.02). Eighteen of 21 (86%) patients with native valve infection were cured or improved compared with 13 of 19 (68%) patients with prosthetic valve endocarditis (p = 0.13). The mean duration of successful fluconazole regimens was 134 days. Twenty of 21 (95%) patients who received fluconazole as chronic suppressive therapy for ≥6 months were cured. Prognosis was independent of Candida species or patient age. Among 23 historical controls managed with fluconazole-containing antifungal therapy plus valvular surgery, survival was 91%.In conclusion, fluconazole-containing, combination antifungal therapy, with or without concomitant valve replacement, and followed by prolonged, perhaps indefinite fluconazole suppression, is effective in patients with Candida endocarditis.     

The predictors of outcome in immunocompetent patients with hematogenous candidiasis.

OBJECTIVE: Clinical parameters that predict outcome in non-immunosuppressed candidemic patients are not fully understood. METHODS: Eighty-one consecutive episodes of candidemia were retrospectively evaluated in 75 patients during 1998-2000. RESULTS: Infection due to Candida albicans was common (n = 30; 37%) followed by Candida glabrata (n = 25; 31%), Candida parapsilosis (n = 14; 17%), Candida tropicalis (n = 6; 7%), Candida krusei (n = 5; 6%), and Candida lusitaniae (n = 1; 1%). Among 70 evaluable patients, 31 (44%) had fungemia-associated mortality; advanced age (P < 0.004), underlying malignancy (P < 0.025), coronary artery disease (P < 0.01), and concurrent non-Candida species fungal infection (P < 0.047) were significant prognosticators of compromised short-term survival by multivariate analysis. Mortality was higher in patients with Candida glabrata (60%) and C. tropicalis (75%) infection compared to 44% deaths in individuals with C. albicans infection (P > 0.1). 11/25 (44%) of non-immunocompromised individuals died and 20/45 (44%) immunosuppressed patients succumbed to fungemia: persistent vs. non-persistent (< 3 days) Candida bloodstream invasion, neutropenia, diabetes mellitus, renal insufficiency, prior antimicrobial therapy, cirrhosis of liver, abdomino-pelvis surgery, and critical-care-unit vs. non critical-care-unit admission did not significantly impact outcome in either group. All 11 infants, including nine with prematurity, survived Candida species bloodstream infection (P < 0.025). CONCLUSIONS: Short-term mortality in candidemic non-immunocompromised patients was comparable to fungemia-associated deaths in immunosuppressed patients. Ischemic heart disease has appeared as a new predictor of unfavorable outcome in patients with hematogenous candidiasis.     

Invasive candidiasis in cancer patients: observations from a randomized clinical trial

BACKGROUND: Invasive candidiasis is a common and serious complication of cancer and its therapy. METHODS: We retrospectively identified patients with malignancies enrolled in a double-blind randomized trial of caspofungin (50 mg/day after a 70 mg loading dose) vs. conventional amphotericin B (0.6-1.0 mg/kg/day) as treatment of documented invasive candidiasis. A favorable response required complete resolution of signs and symptoms plus eradication of the Candida pathogen(s). The primary efficacy analysis used a modified intention-to-treat (MITT) approach that included all patients with a confirmed diagnosis of invasive candidiasis who received > or =1 dose of study medication. RESULTS: 74/224 (33%) patients in the MITT population had active malignancies. 25/30 (83%) hematological malignancies were acute or chronic leukaemias. 22/44 (50%) solid tumors were related to the gastrointestinal tract. Patients with hematological malignancies tended to be younger (median [range] age: 49 [19-74] vs. 59 [19-81] years) and have higher baseline acute physiology and chronic health evaluation (APACHE) II scores (mean [range]: 17 [0-28] vs. 15 [5-35]) than patients with solid tumors. Neutropenia [< or =500/microl] was present on entry in 23 (77%) patients with hematological malignancies and in one (3%) patient with a solid tumor. Candidemia was demonstrated in 56 (88%) cancer patients. C. albicans was the single most frequent isolate in cancer patients, although the majority of cases were caused by non-albicans species. Cancer patients in the caspofungin arm had more hematological malignancies (55 vs. 29%), higher baseline APACHE II scores (>20 in 36 vs. 15%), more frequent neutropenia (42 vs. 24%), and less C. albicans infections (27 vs. 49%) than the amphotericin B-treated cancer patients. Favorable response rates were 11/18 (61%) and 6/12 (50%) for patients with hematological malignancies treated with caspofungin or amphotericin B, respectively; the corresponding outcomes in patients with solid tumors were 12/15 (80%) and 17/29 (59%) for the 2 treatment arms. 7/14 (50%) caspofungin- and 4/10 (40%) amphotericin B-treated patients who were neutropenic on entry responded favorably. All-cause mortality rates during the study for caspofungin recipients were 11/18 (61%) with hematological malignancies and 6/15 (40%) with solid tumors, and for amphotericin recipients were 4/12 (33%) with hematological malignancies and 6/29 (21%) with solid tumors. CONCLUSIONS: Underlying cancers, most commonly leukaemias and gastrointestinal tumors, were present in one-third of patients enrolled in this study of invasive candidiasis. Overall, 70% of caspofungin-treated and 56% of amphotericin B-treated cancer patients responded favorably. Response rates were lower for neutropenic leukaemic patients than for non-neutropenic patients with solid tumors in both treatment groups.     

高龄肺癌住院患者感染真菌性肺炎的调查研究

目的 探讨高龄肺癌患者肺部真菌感染发病的特征.方法 总结住院继发真菌性肺炎患者64例的临床资料.结果 64例患者痰培养的致病真菌以白色假丝酵母菌为主.患者均用过抗生素治疗,痊愈39.1%（25例）,好转42.2%（27例）,好转治愈率为81.3%（52例）;病死率为18.8%（12例）,死亡原因以呼吸衰竭为主.本组临床资料示应用卡泊芬净治疗结束后肝肾功能无明显变化.结论 支气管、肺泡及医院真菌感染的高发生率是老年重症肺炎形成的重要因素.