Division of Hematology-Oncology, Department of Medicine, UCLA Medical Center, University of California-Los Angeles, CA 90095, USA.
Biol Blood Marrow Transplant. 2011 Apr;17(4):507-15. doi: 10.1016/j.bbmt.2010.04.017. Epub 2010 May 9.
Based on favorable results from randomized clinical trials, oral posaconazole has been approved for prophylaxis in neutropenic patients and stem cell transplantation (SCT) recipients. However, routine use of a prophylactic drug may yield different results than those from clinical trials. We collected data on the efficacy, safety, breakthrough infections, and antimicrobial resistance associated with standard long-term posaconazole prophylaxis in adult allogeneic SCT recipients at the UCLA Medical Center. Oral posaconazole (200 mg 3 times daily) was started on day 1 after SCT and continued until day 100. After day 100, posaconazole was continued in patients who still required corticosteroids for prevention or treatment of graft-versus-host disease. From January 2007 through December 2008, 106 consecutive patients received prophylactic posaconazole. Breakthrough invasive fungal infections on posaconazole occurred in 8 patients (7.5%) within 6 months after SCT; 3 additional patients developed invasive fungal infection after discontinuation of prophylactic posaconazole. The infective organisms were Candida (8 cases), Aspergillus (2 cases), and Aspergillus plus Coccidioides immitis (1 case). There were no Zygomycetes infections. Only 2 (both Candida glabrata) of 9 infecting isolates tested were resistant to posaconazole (minimal inhibitory concentration >1 μg/mL). Mortality from invasive fungal infection occurred in 4 patients (3.7%). Except for nausea in 9 patients, no clinical adverse event or laboratory abnormality could be attributed to posaconazole. Mean peak and trough plasma posaconazole concentrations were relatively low (<400 ng/mL) in neutropenic patients with oral mucositis and other factors possibly affecting optimal absorption of posaconazole. These results demonstrate that standard long-term oral posaconazole prophylaxis after allogeneic SCT is safe and associated with few invasive mold infections. However, breakthrough infections caused by posaconazole-susceptible organisms (frequently Candida) may occur at currently recommended prophylactic doses. Thus, strategies to improve posaconazole exposure, including the use of higher doses, administration with an acidic beverage, and restriction of proton pump inhibitors, need to be considered when using prophylactic posaconazole.
基于随机临床试验的良好结果，口服泊沙康唑已被批准用于中性粒细胞减少症患者和干细胞移植（SCT）受者的预防。然而，预防性药物的常规使用可能会产生与临床试验不同的结果。我们收集了在加州大学洛杉矶分校医疗中心接受异基因 SCT 的成年患者中，标准长期泊沙康唑预防的疗效、安全性、突破性感染和与抗菌药物耐药性相关的数据。SCT 后第 1 天开始口服泊沙康唑（每日 3 次，每次 200mg），持续至第 100 天。第 100 天之后，仍需要皮质类固醇预防或治疗移植物抗宿主病的患者继续使用泊沙康唑。从 2007 年 1 月至 2008 年 12 月，106 例连续患者接受了预防性泊沙康唑治疗。SCT 后 6 个月内，8 例（7.5%）患者出现泊沙康唑突破性侵袭性真菌感染；3 例患者在停止预防性泊沙康唑治疗后发生侵袭性真菌感染。感染病原体为念珠菌（8 例）、曲霉（2 例）和曲霉加荚膜组织胞浆菌（1 例）。未发现有接合菌感染。在 9 株感染分离株中，只有 2 株（均为光滑念珠菌）对泊沙康唑耐药（最小抑菌浓度>1μg/ml）。4 例患者（3.7%）因侵袭性真菌感染死亡。除 9 例患者出现恶心外，无临床不良事件或实验室异常可归因于泊沙康唑。中性粒细胞减少症伴口腔黏膜炎和其他可能影响泊沙康唑最佳吸收的因素的患者，其泊沙康唑的平均峰和谷血浆浓度相对较低（<400ng/ml）。这些结果表明，异基因 SCT 后标准长期口服泊沙康唑预防是安全的，与侵袭性霉菌感染发生率低有关。然而，目前推荐的预防性剂量可能会发生泊沙康唑敏感病原体（常为念珠菌）引起的突破性感染。因此，在使用预防性泊沙康唑时，需要考虑提高泊沙康唑暴露的策略，包括使用更高剂量、与酸性饮料一起给药和限制质子泵抑制剂的使用。
