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雾化脂质两性霉素 B 作为侵袭性肺曲霉病患者的补充治疗和/或二级预防:一项单中心经验。

Aerosolized Lipid Amphotericin B for Complementary Therapy and/or Secondary Prophylaxis in Patients with Invasive Pulmonary Aspergillosis: A Single-Center Experience.

机构信息

Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Carretera Colmenar km 9,1, 28034, Madrid, Spain.

Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain.

出版信息

Mycopathologia. 2019 Apr;184(2):239-250. doi: 10.1007/s11046-019-00331-0. Epub 2019 Mar 22.

Abstract

BACKGROUND

Experience with aerosolized lipid amphotericin B (aeLAB) as therapy or secondary prophylaxis in patients with invasive pulmonary aspergillosis (IPA) is anecdotal.

METHODS

We performed a single-center retrospective cohort study to evaluate the efficacy of systemic antifungal therapy with and without aeLAB in patients with proven or probable IPA. Complete or partial response at 3 months was the primary end-point. Clinical response and mortality at 12 months, occurrence of adverse drug reactions and respiratory fungal colonization were secondary end-point.

RESULTS

Eleven patients (39%) received aeLAB in addition to systemic antifungal therapy (group A), and 22 (61%) received systemic antifungal therapy only (group B). The use of aeLAB was not standardized. Amphotericin B lipid complex was used in all patients but one, who received liposomal amphotericin B. Five patients received aeLAB as antifungal complementary therapy and 6 received it as secondary prophylaxis. Except for the requirement of inhaled corticosteroids and home oxygen therapy, more frequent in group A, both groups were similar in baseline conditions. A better (nonsignificant) clinical outcome was observed at 3 months in patients receiving aeLAB. Only uncontrolled baseline condition was associated with one-year mortality in univariate analysis (p = 0.002). A multivariate Cox regression analysis suggests that aeLAB, corrected for uncontrolled underlying disease, reduces mortality at 12 months (HR 0.258; 95% CI 0.072-0.922; p = 0.037).

CONCLUSION

Although no significant difference was observed in the main variable (3-month clinical response) and in spite of methodological limitations of the study, the possible survival benefit of aeLAB, adjusted for the control of the underlying disease, could justify the performance of well-controlled studies with a greater number of patients.

摘要

背景

经验与雾化脂质两性霉素 B (aeLAB) 作为治疗或二线预防侵袭性肺曲霉病 (IPA) 患者是轶事。

方法

我们进行了一项单中心回顾性队列研究,以评估全身抗真菌治疗与雾化脂质两性霉素 B 联合或不联合治疗确诊或可能 IPA 患者的疗效。3 个月时完全或部分缓解是主要终点。12 个月时的临床反应和死亡率、不良反应和呼吸道真菌定植的发生是次要终点。

结果

11 例(39%)患者在全身抗真菌治疗的基础上加用雾化脂质两性霉素 B(A 组),22 例(61%)仅接受全身抗真菌治疗(B 组)。雾化脂质两性霉素 B 的使用未标准化。所有患者均使用两性霉素 B 脂质复合物,但有 1 例患者使用脂质体两性霉素 B。5 例患者使用雾化脂质两性霉素 B 作为抗真菌辅助治疗,6 例患者作为二线预防使用。除需要吸入性皮质类固醇和家庭氧疗外,A 组患者更为常见,但两组患者的基线条件相似。接受雾化脂质两性霉素 B 治疗的患者在 3 个月时观察到更好(无统计学意义)的临床结果。在单变量分析中,只有未控制的基线条件与 1 年死亡率相关(p=0.002)。多变量 Cox 回归分析表明,在调整未控制的基础疾病后,雾化脂质两性霉素 B 降低 12 个月死亡率(HR 0.258;95%CI 0.072-0.922;p=0.037)。

结论

尽管主要变量(3 个月临床反应)未观察到显著差异,且研究存在方法学局限性,但在调整基础疾病控制后,雾化脂质两性霉素 B 可能具有生存获益,这可能证明进行更多患者的严格对照研究是合理的。

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