低剂量氟康唑对急性白血病患者侵袭性念珠菌感染一级预防的疗效：一项双盲随机临床试验

Efficacy of Low-Dose Fluconazole for Primary Prophylaxis of Invasive Candida Infections in Patients With Acute Leukemia: A Double-Blind Randomized Clinical Trial.

作者信息

Savary-Kouzehkonan Roghayeh, Sadeghi Kourosh, Rad Soroush, Alijani Neda, Baseri Zohreh, Vaezi Mohammad, Mousavi Seyed Asadollah, Shahrami Bita

机构信息

Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Hematology, Oncology, and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology, and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Cancer Med. 2025 Apr;14(7):e70837. doi: 10.1002/cam4.70837.

DOI:10.1002/cam4.70837

PMID:40152076

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11950833/

Abstract

BACKGROUND

Invasive fungal infections (IFIs), particularly Candida infections, are a significant cause of morbidity and mortality in patients with acute leukemia. While fluconazole is widely used for prophylaxis, the optimal dosing regimen remains uncertain. This study aimed to evaluate the efficacy of low-dose fluconazole for primary prophylaxis against invasive Candida infections in patients with acute leukemia receiving intensive chemotherapy.

METHODS

A double-blind, randomized clinical trial was conducted with patients diagnosed with acute leukemia. Patients were assigned to receive either low-dose (150 mg/day) or standard high-dose (400 mg/day) fluconazole for primary prophylaxis against invasive Candida infections during intensive chemotherapy. The primary outcomes were the efficacy of antifungal prophylaxis and the safety profile.

RESULTS

A total of 120 patients (60 per group) were enrolled. The overall incidence of Candida infections was similar between the groups (p = 0.615). Candida colonization was higher in the low-dose fluconazole group during the first week, particularly with non-albicans Candida at oral and subaxillary sites (p < 0.001). However, by the third week, both groups showed a significant decline in colonization, with the reduction in the oral cavity being statistically significant (p = 0.03). Aspergillosis occurred in 38.3% of patients, with no significant difference between groups (p > 0.99). Adverse events were similar in both groups (p > 0.05).

CONCLUSION

Low-dose fluconazole is an effective alternative to high-dose regimens for preventing Candida infections in acute leukemia patients, with similar efficacy and safety. The rising threat of aspergillosis highlights the need for targeted prophylaxis. Further research is needed to refine strategies for high-risk patients.

TRIAL REGISTRATION

Iranian Registry of Clinical Trials (IRCT) number: IRCT20140818018842N37.

摘要

背景

侵袭性真菌感染（IFI），尤其是念珠菌感染，是急性白血病患者发病和死亡的重要原因。虽然氟康唑广泛用于预防，但最佳给药方案仍不确定。本研究旨在评估低剂量氟康唑对接受强化化疗的急性白血病患者原发性预防侵袭性念珠菌感染的疗效。

方法

对诊断为急性白血病的患者进行了一项双盲、随机临床试验。患者被分配接受低剂量（150毫克/天）或标准高剂量（400毫克/天）氟康唑，以在强化化疗期间原发性预防侵袭性念珠菌感染。主要结局是抗真菌预防的疗效和安全性。

结果

共纳入120例患者（每组60例）。两组念珠菌感染的总体发生率相似（p = 0.615）。低剂量氟康唑组在第一周念珠菌定植率较高，尤其是在口腔和腋下部位的非白色念珠菌（p < 0.001）。然而，到第三周时，两组定植率均显著下降，口腔内的下降具有统计学意义（p = 0.03）。38.3%的患者发生曲霉病，两组之间无显著差异（p > 0.99）。两组不良事件相似（p > 0.05）。