PDF(Pubmed)
Abstract：
Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality in de-novo acute myeloid leukemia patients receiving induction chemotherapy. Despite using posaconazole, a broad-spectrum antifungal, for IFI prophylaxis, the breakthrough IFI rate is high in the real-world setting. One of the reasons could be frequent suboptimal plasma posaconazole levels. In the present study, we evaluated if therapeutic drug monitoring (TDM) guided posaconazole prophylaxis can reduce the IFI rates in comparison to a historical cohort. We enrolled 90 patients, > / = 16 years of age, without baseline IFIs, planned for remission induction therapy. All patients were started on posaconazole suspension 200 mg TDS and the dose was increased in a stepwise manner if trough levels were found to be suboptimal (< 350 ng/ml for day 2 or < 700 ng/ml subsequently). The TDM based approach resulted in a significant decline in breakthrough IFI rates (18% versus 52%, P < 0.0001) A total of 69 patients (78%) required dose escalation. Thirty-one patients required change in antifungals due to either suboptimal levels, persistent fever, diarrhoea or vomiting. We could not demonstrate an exposure-response relationship but the difference in IFI rates in patients with a median posaconazole level > / = 700 ng/ml (0%) and < 700 ng/ml (21.6%) was clinically meaningful. Posaconazole levels were found to be significantly lower in patients on antacids and prokinetics. The incidence of posaconazole-related grade 3 toxicity was low (2.3%). Thus TDM-based dosing of posaconazole helps reduce breakthrough IFI rate and should be a part of posaconazole prophylaxis.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12288-023-01709-3.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12288-023-01709-3.
摘要：
侵袭性真菌感染（IFIs）是接受诱导化疗的新生急性髓细胞性白血病患者发病和死亡的重要原因。尽管使用泊沙康唑,广谱抗真菌药,对于FI预防，在现实世界中，突破性的FI率很高。原因之一可能是血浆泊沙康唑水平经常次优。在本研究中,与历史队列相比,我们评估了治疗药物监测(TDM)指导的泊沙康唑预防是否能降低FI发生率.我们招募了90名患者，>/=16岁，没有基线IFIs，计划缓解诱导治疗。所有患者开始服用泊沙康唑悬浮液200mgTDS，如果发现波谷水平次优（第2天<350ng/ml或随后<700ng/ml），则剂量逐步增加。基于TDM的方法导致了突破性的FI率显著下降(18%对52%，P<0.0001)共有69名患者(78%)需要剂量递增。31名患者由于任一次优水平而需要更换抗真菌药物，持续发烧，腹泻或呕吐。我们无法证明暴露-反应关系，但泊沙康唑水平中位数>/=700ng/ml（0％）和<700ng/ml（21.6％）的患者的国际利率差异具有临床意义。在抗酸剂和前动力的患者中，泊沙康唑的水平显着降低。泊沙康唑相关的3级毒性发生率较低(2.3%)。因此，以TDM为基础的泊沙康唑的给药有助于降低突破性的FI率，应作为泊沙康唑预防的一部分。
■在线版本包含补充材料，可在10.1007/s12288-023-01709-3获得。
■在线版本包含补充材料，可在10.1007/s12288-023-01709-3获得。
