Patterson Thomas F, Boucher Helen W, Herbrecht Raoul, Denning David W, Lortholary Olivier, Ribaud Patricia, Rubin Robert H, Wingard John R, DePauw Ben, Schlamm Haran T, Troke Peter, Bennett John E
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Clin Infect Dis. 2005 Nov 15;41(10):1448-52. doi: 10.1086/497126. Epub 2005 Oct 13.
In a previous randomized trial of voriconazole versus amphotericin B deoxycholate for primary therapy of invasive aspergillosis, voriconazole demonstrated superior efficacy and better survival. In that trial, treatment with voriconazole or amphotericin B deoxycholate could be followed with other licensed antifungal therapies (OLAT). Here, we report the impact of OLAT on the outcome of patients with invasive aspergillosis.
Data on dose, duration, and the reason for switching to the first OLAT were analyzed, and outcome at week 12 was assessed.
Fewer patients in the voriconazole group (52 [36%] of 144) switched to OLAT, compared with patients in the amphotericin B deoxycholate group (107 [80%] of 133). Lipid formulations of amphotericin B were the most common OLAT (38% of patients). Switches were made because of intolerance or insufficient response in 70% for patients in the amphotericin B deoxycholate group, compared with 24% of patients in the voriconazole group. Favorable responses to OLAT in the amphotericin B deoxycholate group occurred in only 19% of patients with initial insufficient response and 38% of patients with intolerance. Salvage therapy with a lipid formulation of amphotericin B after initial treatment with amphotericin B deoxycholate was successful for only 30% of patients (14 of 47). Treatment success among patients randomized to receive amphotericin B, including those whose treatment was switched to OLAT, was 32%, compared with 55% among patients who received voriconazole alone (P<.001).
This study highlights the limited efficacy of salvage antifungal therapy, including therapy with lipid formulations of amphotericin B, and demonstrates the importance of effective initial therapy in invasive aspergillosis.
在一项先前进行的伏立康唑与两性霉素B脱氧胆酸盐用于侵袭性曲霉病初始治疗的随机试验中，伏立康唑显示出更好的疗效和更高的生存率。在该试验中，伏立康唑或两性霉素B脱氧胆酸盐治疗后可继以其他已获许可的抗真菌治疗（OLAT）。在此，我们报告OLAT对侵袭性曲霉病患者结局的影响。
分析了关于首次OLAT的剂量、疗程及换药原因的数据，并评估了第12周时的结局。
与两性霉素B脱氧胆酸盐组患者（133例中的107例[80%]）相比，伏立康唑组中换药至OLAT的患者较少（144例中的52例[36%]）。两性霉素B的脂质制剂是最常用的OLAT（占患者的38%）。两性霉素B脱氧胆酸盐组中70%的患者因不耐受或反应不足而换药，相比之下伏立康唑组为24%。两性霉素B脱氧胆酸盐组中，初始反应不足的患者仅有19%、不耐受的患者仅有38%对OLAT有良好反应。两性霉素B脱氧胆酸盐初始治疗后采用两性霉素B脂质制剂进行挽救治疗，仅30%的患者（47例中的14例）成功。随机接受两性霉素B治疗的患者（包括那些治疗改为OLAT的患者）的治疗成功率为32%，而单独接受伏立康唑治疗的患者为55%（P<0.001）。
本研究强调了挽救性抗真菌治疗（包括两性霉素B脂质制剂治疗）的疗效有限，并证明了侵袭性曲霉病有效初始治疗的重要性。
