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[德国实体器官移植后使用卡泊芬净:侵袭性真菌感染治疗的观察性研究]

[Caspofungin after solid organ transplantation in Germany: observational study on treatment of invasive fungal infections].

作者信息

Lichtenstern C, Pratschke J, Schulz U, Schmoeckel M, Knitsch W, Kaskel P, Krobot K J, Weigand M A, Winkler M

机构信息

Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Giessen und Marburg, Standort Giessen, Rudolf-Buchheim Str. 7, 35385, Giessen, Deutschland.

出版信息

Anaesthesist. 2010 Dec;59(12):1083-90. doi: 10.1007/s00101-010-1795-6. Epub 2010 Nov 12.

Abstract

BACKGROUND

This study was a pre-planned country-specific secondary analysis of results in Germany from a multinational multicenter observational study to retrospectively evaluate clinical outcomes with caspofungin in patients with probable and proven invasive fungal infection following solid organ transplantation (SOT).

METHODS

Data were retrospectively collected on a single episode of invasive fungal infection (IFI) in patients who had a SOT between January 2004 and June 2007. Effectiveness was reported as the proportion of patients who received at least five doses of caspofungin with a favorable (complete or partial) response. Safety was assessed for patients who received at least one dose of caspofungin. Descriptive statistics were employed for all evaluations.

RESULTS

A total of 41 SOT patients (27 male, 14 female; median age 56 years, median APACHE II score at start of caspofungin therapy 23) were enrolled from 5 sites in Germany. Organs transplanted were mainly heart (51%) and liver (46%). Prevalent risk factors for IFI at baseline were use of central venous catheter (37 out of 41 patients, 90%), steroid use (37 out of 41 patients, 90%), recent stay in intensive care (36 out of 41 patients, 88%),and duration of SOT procedure >5 hours (21 out of 41 patients, 51%). Candidiasis was diagnosed in 34 patients (83%) and aspergillosis in 10 patients (24%). The lungs were the most common site of IFI (21 out of 41, 51%). Caspofungin as monotherapy was received by 28 patients (68%); 6 patients (15%) received caspofungin as salvage therapy for IFI, in most cases because they were refractory to prior antifungal drugs. Immunosuppressants were administered with caspofungin in 39 out of 41 patients (95%). In subjects with at least 5 doses of caspofungin (modified intention to treat population) the favorable response rate at the end of caspofungin therapy was 88% overall, 29 out of 33 patients; 95% confidence interval (95%-CI) 72-97%), 86% (19 out of 22 patients) with monotherapy and 91% (10 out of 11 patients) with combination therapy. No (serious) adverse events or drug interactions related to treatment with caspofungin were reported. The overall survival rate was 79% (26 out of 33 patients; 95%-CI 61-91%) at 7 days after completion of caspofungin treatment.

CONCLUSION

Caspofungin was found to be an effective treatment of probable and proven invasive fungal infections in patients following SOT in Germany.

摘要

背景

本研究是一项针对德国地区的预先计划的国别特异性二次分析,该分析基于一项跨国多中心观察性研究的结果,旨在回顾性评估卡泊芬净对实体器官移植(SOT)后可能患有及已确诊侵袭性真菌感染患者的临床疗效。

方法

回顾性收集2004年1月至2007年6月期间接受SOT且发生过单次侵袭性真菌感染(IFI)患者的数据。疗效以接受至少五剂卡泊芬净且有良好(完全或部分)反应的患者比例表示。对接受至少一剂卡泊芬净的患者进行安全性评估。所有评估均采用描述性统计方法。

结果

从德国的5个地点招募了41例SOT患者(男性27例,女性14例;中位年龄56岁,卡泊芬净治疗开始时的中位急性生理与慢性健康状况评分系统II评分为23)。移植的器官主要是心脏(51%)和肝脏(46%)。基线时IFI的常见危险因素包括使用中心静脉导管(41例患者中的37例,90%)、使用类固醇(41例患者中的37例,90%)、近期入住重症监护病房(41例患者中的36例,88%)以及SOT手术持续时间>5小时(41例患者中的21例,51%)。34例患者(83%)诊断为念珠菌病,10例患者(24%)诊断为曲霉病。肺部是IFI最常见的部位(41例中的21例,51%)。28例患者(68%)接受卡泊芬净单药治疗;6例患者(15%)接受卡泊芬净作为IFI的挽救治疗,大多数情况下是因为他们对先前的抗真菌药物耐药。41例患者中有39例(95%)在使用卡泊芬净时同时使用免疫抑制剂。在接受至少5剂卡泊芬净的受试者(改良意向性治疗人群)中,卡泊芬净治疗结束时的总体良好反应率为88%,33例患者中有29例;95%置信区间(95%-CI)为72-97%),单药治疗组为86%(22例患者中的19例),联合治疗组为91%(11例患者中的10例)。未报告与卡泊芬净治疗相关的(严重)不良事件或药物相互作用。卡泊芬净治疗完成后7天的总体生存率为79%(33例患者中的26例;95%-CI 61-91%)。

结论

在德国,发现卡泊芬净是治疗SOT后患者可能患有及已确诊侵袭性真菌感染的有效药物。

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