Groetzner Jan, Kaczmarek Ingo, Wittwer Thorsten, Strauch Justus, Meiser Bruno, Wahlers Thorsten, Daebritz Sabine, Reichart Bruno
Department of Cardio-Thoracic Surgery, Cologne University Hospital, Cologne, Germany.
J Heart Lung Transplant. 2008 Jan;27(1):1-6. doi: 10.1016/j.healun.2007.10.002.
Although amphotericin was the gold standard in the treatment of invasive aspergillosis in transplant recipients, nephrotoxicity and lack of efficacy often limits its use. Itraconazole is better tolerated but less efficacious and influences immunosuppressant trough levels significantly. We report our first clinical experience with the use of caspofungin as first-line therapy in heart and lung transplant recipients with invasive aspergillosis.
Caspofungin was administered at 50 to 70 mg/day in heart and lung transplant recipients with renal impairment while invasive aspergillosis was diagnosed and classified. Aspergillus serology, serologic inflammatory markers, and X-rays were taken to monitor infectious activity. Creatinine and immunosuppressant trough levels were monitored closely.
Invasive aspergillosis was diagnosed by chest X-ray, serology, and positive sputum in 1 heart-lung, 7 heart, and 4 single-lung transplant recipients, and caspofungin was administered for a mean time of 21 +/- 9 days. Basic immunosuppressants were tacrolimus in 9 patients or cyclosporine in 3. Complete remission was achieved in 10 patients (83%). Adverse effects of caspofungin were fever in 6, diarrhea in 3, and neutropenia in 1. Renal function remained stable (3.2 +/- 1 mg/dl before vs 2.3 +/- 0.9 mg/dl after, p = 0.07). Trough levels of all immunosuppressants did not change significantly during caspofungin treatment (10.9 +/- 4.1 ng/ml before vs 9.9 +/- 4.0 ng/ml after [p = 0.31] for tacrolimus; 214 +/- 98 ng/ml before vs 229 +/- 88 ng/ml after [p = 0.41] for cyclosporin A), while the administered dosage remained stable.
In heart and lung transplant recipients with invasive aspergillosis, caspofungin seemed to be an effective anti-fungal agent with a promising safety profile. Further prospective randomized trials are needed to investigate an advantageous role of caspofungin in the treatment of invasive aspergillosis.
尽管两性霉素曾是移植受者侵袭性曲霉病治疗的金标准,但肾毒性和疗效欠佳常限制其应用。伊曲康唑耐受性较好,但疗效较差且会显著影响免疫抑制剂的谷浓度。我们报告了在心肺移植受者侵袭性曲霉病中使用卡泊芬净作为一线治疗的首例临床经验。
在诊断并分类侵袭性曲霉病的肾功能受损的心肺移植受者中,以每日50至70毫克的剂量给予卡泊芬净。检测曲霉血清学、血清学炎症标志物及进行X线检查以监测感染活动。密切监测肌酐及免疫抑制剂谷浓度。
通过胸部X线、血清学及痰菌阳性,在1例心肺移植、7例心脏移植和4例单肺移植受者中诊断出侵袭性曲霉病,卡泊芬净平均使用时间为21±9天。基础免疫抑制剂在9例患者中为他克莫司,3例为环孢素。10例患者(83%)实现完全缓解。卡泊芬净的不良反应为6例发热、3例腹泻和1例中性粒细胞减少。肾功能保持稳定(治疗前3.2±1毫克/分升,治疗后2.3±0.9毫克/分升,p = 0.07)。在卡泊芬净治疗期间,所有免疫抑制剂的谷浓度均无显著变化(他克莫司治疗前10.9±4.1纳克/毫升,治疗后9.9±4.0纳克/毫升[p = 0.31];环孢素A治疗前214±98纳克/毫升,治疗后229±88纳克/毫升[p = 0.41]),而给药剂量保持稳定。
在患有侵袭性曲霉病的心肺移植受者中,卡泊芬净似乎是一种有效的抗真菌药物,具有良好的安全性。需要进一步的前瞻性随机试验来研究卡泊芬净在侵袭性曲霉病治疗中的优势作用。