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鼻窦毛霉菌病与脂质体两性霉素B:剂量优化探索

Sinonasal mucormycosis and liposomal amphotericin B: A quest for dose optimization.

作者信息

Kajal Smile, Naeem Syed Shariq, Gupta Pooja, Kairo Arvind Kumar, Ahmed Anam, Verma Prankur, Saini Ashish

机构信息

Department of Otorhinolaryngology and Head-Neck Surgery, All India Institute of Medical Sciences, New Delhi, India.

Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Indian J Pharmacol. 2022 Mar-Apr;54(2):90-96. doi: 10.4103/ijp.ijp_644_21.

Abstract

OBJECTIVES

Sinonasal mucormycosis is a serious fungal infection. Early diagnosis and prompt antifungal therapy along with surgical intervention is the key to its management. Liposomal amphotericin B (LAmB) given intravenously is the antifungal agent of choice. However, the current literature is not clear on its optimum dosage. We did a retrospective study to find the optimum dose of LAmB in cases with sinonasal mucormycosis.

MATERIALS AND METHODS

Thirty patients diagnosed with mucormycosis involving sinonasal, rhino-orbital, or rhino-orbito-cerebral regions and receiving only LAmB as pharmacotherapy were included in our retrospective study from 2017 to 2020. A multiple logistic regression model was developed to correlate the total dose of LAmB and other parameters with the final outcome which was defined clinico-radiologically as improved, worsened, or death. The dose of LAmB which led to the first significant change in urea, creatinine, and potassium levels was also determined.

RESULTS

The model showed a good fit in goodness-to-fit analysis (Pearson = 0.999, deviance = 0.995), while the likelihood ratio was statistically significant (0.001). The overall model prediction was 83.3%. However, the correlation of outcome with any of the variables, including mean LAmB dose per kilogram (82.2 ± 13.02 mg/kg), was statistically not significant.

CONCLUSION

Many patient-related factors (such as age, comorbidities, extent of the disease, and side effects from LAmB therapy), which vary on a case-to-case basis, contribute to the outcome in a mucormycosis patient. The optimum dose of LAmB for improved outcome still requires individualization guided by experience, till well-designed studies address the question.

摘要

目的

鼻窦毛霉菌病是一种严重的真菌感染。早期诊断、及时的抗真菌治疗以及手术干预是其治疗的关键。静脉注射脂质体两性霉素B(LAmB)是首选的抗真菌药物。然而,目前的文献对于其最佳剂量尚无定论。我们进行了一项回顾性研究,以确定鼻窦毛霉菌病患者中LAmB的最佳剂量。

材料与方法

2017年至2020年期间,我们的回顾性研究纳入了30例被诊断为毛霉菌病累及鼻窦、鼻眶或鼻眶脑区域且仅接受LAmB作为药物治疗的患者。建立了一个多元逻辑回归模型,将LAmB的总剂量和其他参数与最终结局相关联,最终结局根据临床放射学定义为改善、恶化或死亡。还确定了导致尿素、肌酐和钾水平首次出现显著变化的LAmB剂量。

结果

该模型在拟合优度分析中显示出良好的拟合度(Pearson = 0.999,偏差 = 0.995),而似然比具有统计学意义(0.001)。总体模型预测率为83.3%。然而,结局与任何变量的相关性,包括每千克平均LAmB剂量(82.2 ± 13.02 mg/kg),在统计学上均无显著意义。

结论

许多与患者相关的因素(如年龄、合并症、疾病范围以及LAmB治疗的副作用)因病例而异,这些因素会影响毛霉菌病患者的结局。在设计完善的研究解决这个问题之前,为改善结局而确定的LAmB最佳剂量仍需要根据经验进行个体化调整。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b5/9249146/0bb6cb21bd61/IJPharm-54-90-g001.jpg

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