Triazole antifungals used for prophylaxis and treatment of invasive fungal disease in adult haematology patients: Trough serum concentrations in relation to outcome
Triazole antifungals used for prophylaxis and treatment of invasive fungal disease in adult haematology patients: Trough serum concentrations in relation to outcome
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DOI：
10.1093/mmy/myw031
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发表时间：
2016-10-01
期刊：
影响因子：
2.9
通讯作者：
Pagliuca, Antonio
中科院分区：
文献类型：
--
作者：
Ceesay, M. Mansour;Couchman, Lewis;Pagliuca, Antonio
三唑类抗真菌药物广泛用于侵袭性真菌病的预防和治疗。有效性可能取决于达到最低有效血浆浓度。本研究的目的是确定给予这些药物的患者中达到推荐浓度的样本比例与结局的关系。住院患者规定的标准剂量的氟康唑，伊曲康唑溶液，泊沙康唑混悬液，或口服伏立康唑至少一周进行了研究。使用经验证的方法测量给药前血清三唑浓度。共有90名患者的359份样本。每例患者的中位（范围）样本数为3（1-13），氟康唑、伊曲康唑、泊沙康唑的中位（范围）（预防），泊沙康唑伏立康唑血清浓度分别为5.64（0.11-18）、0.57（0-5.3）、0.31（0.02-2.5）、0.65（0.02-2.5）和0.95（0.10-5.4）mg/l。伊曲康唑、泊沙康唑（> 0.7 mg/l预防）、泊沙康唑（治疗）和伏立康唑达到推荐给药前浓度的样本数量分别为98（54%）、9（20%）、2（18%）和29（49%）。与没有IFD证据的患者相比，在证实/可能IFD的患者之间未检测到中位三唑谷浓度的显著差异。然而，在10份样本（7例患者）中未检测到伊曲康唑。达到推荐的泊沙康唑谷浓度的患者数量较少，这可能解释了在处方该药物的患者中观察到的高突破IFD率。除氟康唑外，达到推荐三唑谷浓度的标准剂量三唑类药物的患者数量较少。前瞻性使用血清三唑测量试验可能改善伊曲康唑、泊沙康唑和伏立康唑的结局。
Triazole antifungal drugs are widely used for the prophylaxis and treatment of invasive fungal disease (IFD). Efficacy may depend on attaining minimum effective plasma concentrations. The aim of this study was to ascertain the proportion of samples in which the recommended concentrations were achieved in patients given these drugs in relation to outcome. In-patients prescribed standard doses of fluconazole, itraconazole solution, posaconazole suspension, or oral voriconazole for at least one week were studied. Pre-dose serum triazole concentrations were measured using validated methods. There were 359 samples from 90 patients. The median (range) number of samples per patient was 3 (1-13), and the median (range) fluconazole, itraconazole, posaconazole (prophylaxis), posaconazole (treatment), and voriconazole serum concentrations were 5.64 (0.11-18), 0.57 (0-5.3), 0.31 (0.02-2.5), 0.65 (0.02-2.5), and 0.95 (0.10-5.4) mg/l, respectively. The number of samples in which the recommended pre-dose concentrations were achieved was 98 (54%), 9 (20%), 2 (18%), and 29 (49%) for itraconazole, posaconazole (> 0.7 mg/l prophylaxis), posaconazole (treatment), and voriconazole, respectively. No significant differences were detected in the median triazole trough concentrations between patients with proven/probable IFD compared to those with no evidence of IFD. However, itraconazole was not detected in 10 samples (7 patients). The small number of patients who achieved the recommended trough posaconazole concentrations may explain the high rate of break-through IFD observed in patients prescribed this drug. Except for fluconazole, the number of patients prescribed standard doses of triazoles who achieved recommended trough triazole concentrations was low. The prospective use of serum triazole measurements assay may have improved outcomes with itraconazole, posaconazole, and with voriconazole.