Département d'Anesthésie-Réanimation Adulte-SAMU de Paris, Hôpital Necker; Assistance Publique-Hôpitaux de Paris, University Paris Cité, Paris, France.
Université Sorbonne Paris Nord, IAME, INSERM, Paris, France; UF de Pharmacologie, Hôpital Jean Verdier, APHP, Bondy, France.
Int J Antimicrob Agents. 2023 Dec;62(6):107007. doi: 10.1016/j.ijantimicag.2023.107007. Epub 2023 Oct 13.
Critically ill patients frequently require continuous renal replacement therapy. Echinocandins are recommended as first-line treatment of candidemia. Preliminary results suggested echinocandin sequestration in a polyacrylonitrile filter. The present study aimed to determine whether increasing the dose might balance sequestration.
An STX filter (Baxter-Gambro) was used. A liquid chromatography-mass spectrometry method was used for dosage of caspofungin. In vitro drug disposition was evaluated by NeckEpur (Neckepur, Versailles, France) technology using a crystalloid medium instead of diluted/reconstituted blood, focusing on the disposition of the unbound fraction of drugs. Two concentrations were assessed.
At the low dose, the mean measured initial concentration in the central compartment (CC) was 5.1 ± 0.6 mg/L. One hundred percent of the initial amount was eliminated from the CC within the 6-h session. The mean total clearance from the CC was 9.6 ± 2.5 L/h. The mean percentages of elimination resulting from sequestration and diafiltration were 96.0 ± 5.0 and 4.0 ± 5.2%, respectively. At high dose, the mean measured initial concentration in the CC was 13.1 mg/L. One hundred percent of the initial amount was eliminated from the CC within the 6-h session. The mean total clearance from the CC was 9.5 L/h. The mean percentages of elimination resulting from sequestration and filtration were 88.5% and 11.5%, respectively.
Increasing the dose does not mitigate caspofungin sequestration in the STX filter. The results raise caution about the simultaneous use of caspofungin and polyacrylonitrile-derived filters. Intermittent modes of renal replacement therapy might be considered. For sensitive species, fluconazole might be an alternative.
危重症患者常需连续肾脏替代治疗。棘白菌素类被推荐为念珠菌血症的一线治疗药物。初步结果表明，棘白菌素类在丙烯腈滤器中被隔离。本研究旨在确定增加剂量是否能平衡隔离作用。
使用 STX 滤器（百特-甘布罗）。采用液相色谱-质谱法测定卡泊芬净的剂量。采用 NeckEpur（法国凡尔赛的 Neckepur）技术，使用晶体介质代替稀释/再配制的血液，评估药物的体外处置，重点关注药物未结合部分的处置。评估了两种浓度。
在低剂量时，中央室（CC）的初始测量浓度的平均值为 5.1±0.6mg/L。在 6 小时的疗程内，100%的初始量从 CC 中消除。CC 的平均总清除率为 9.6±2.5L/h。由于隔离和透析过滤导致的消除百分比分别为 96.0±5.0%和 4.0±5.2%。在高剂量时，CC 的初始测量浓度的平均值为 13.1mg/L。在 6 小时的疗程内，100%的初始量从 CC 中消除。CC 的平均总清除率为 9.5L/h。由于隔离和过滤导致的消除百分比分别为 88.5%和 11.5%。
增加剂量并不能减轻 STX 滤器中卡泊芬净的隔离作用。这些结果对棘白菌素类和丙烯腈衍生滤器同时使用提出了警告。可能需要考虑间歇性肾脏替代治疗模式。对于敏感物种，氟康唑可能是一种替代药物。
