PDF(Pubmed)
Abstract：
BACKGROUND: Therapeutic drug monitoring (TDM) of anti-infectives such as linezolid is routinely performed in blood of intensive care unit (ICU) patients to optimize target attainment. However, the concentration at the site of infection is considered more important for a successful therapy. Until now, bronchoalveolar lavage (BAL) is the gold standard to measure intrapulmonary concentrations of anti-infective agents. However, it is an invasive method and unsuitable for regular TDM. The aim of this proof-of-concept study was to investigate whether it is possible to reliably determine the intrapulmonary concentration of linezolid from endotracheal aspiration (ENTA).
METHODS: Intubated ICU patients receiving 600 mg intravenous linezolid twice daily were examined in steady state. First, preliminary experiments were performed in six patients to investigate which patients are suitable for linezolid measurement in ENTA. In a second step, trough and peak linezolid concentrations of plasma and ENTA were determined in nine suitable patients.
RESULTS: Linezolid can validly be detected in ENTA with viscous texture and > 0.5 mL volume. The mean (SD) linezolid trough concentration was 2.02 (1.27) mg/L in plasma and 1.60 (1.36) mg/L in ENTA, resulting in a median lung penetration rate of 104%. The mean (SD) peak concentration in plasma and ENTA was 10.77 (5.93) and 4.74 (2.66) mg/L.
CONCLUSIONS: Linezolid can validly be determined in ENTA with an adequate texture and volume. The penetration rate is comparable to already published BAL concentrations. This method might offer a simple and non-invasive method for TDM at the site of infection \"lung\". Due to promising results of the feasibility study, comparison of ENTA and BAL in the same patient should be investigated in a further trial.
METHODS: Intubated ICU patients receiving 600 mg intravenous linezolid twice daily were examined in steady state. First, preliminary experiments were performed in six patients to investigate which patients are suitable for linezolid measurement in ENTA. In a second step, trough and peak linezolid concentrations of plasma and ENTA were determined in nine suitable patients.
RESULTS: Linezolid can validly be detected in ENTA with viscous texture and > 0.5 mL volume. The mean (SD) linezolid trough concentration was 2.02 (1.27) mg/L in plasma and 1.60 (1.36) mg/L in ENTA, resulting in a median lung penetration rate of 104%. The mean (SD) peak concentration in plasma and ENTA was 10.77 (5.93) and 4.74 (2.66) mg/L.
CONCLUSIONS: Linezolid can validly be determined in ENTA with an adequate texture and volume. The penetration rate is comparable to already published BAL concentrations. This method might offer a simple and non-invasive method for TDM at the site of infection \"lung\". Due to promising results of the feasibility study, comparison of ENTA and BAL in the same patient should be investigated in a further trial.
摘要：
背景：抗感染药物如利奈唑胺的治疗药物监测（TDM）通常在重症监护病房（ICU）患者的血液中进行，以优化目标实现。然而,感染部位的浓度被认为对成功的治疗更为重要。直到现在,支气管肺泡灌洗(BAL)是测定肺内抗感染药物浓度的金标准.然而,这是一种侵入性方法，不适合常规TDM。这项概念验证研究的目的是研究是否有可能通过气管内抽吸（ENTA）可靠地确定利奈唑胺的肺内浓度。
方法：对每天两次静脉注射600mg利奈唑胺的插管ICU患者进行稳态检查。首先,在6例患者中进行了初步实验，以研究哪些患者适合在ENTA中进行利奈唑胺测量。第二步,在9例合适的患者中测定了利奈唑胺的血浆和ENTA的谷和峰浓度.
结果：利奈唑胺可以在具有粘性质地和>0.5mL体积的ENTA中有效检测到。平均（SD）利奈唑胺谷浓度在血浆中为2.02（1.27）mg/L，在ENTA中为1.60（1.36）mg/L，导致肺穿透率中位数为104％。血浆和ENTA的平均（SD）峰浓度为10.77（5.93）和4.74（2.66）mg/L。
结论：利奈唑胺可以在具有足够质地和体积的ENTA中有效测定。渗透率与已经公布的BAL浓度相当。这种方法可能为感染部位“肺”的TDM提供一种简单而非侵入性的方法。由于可行性研究的有希望的结果，同一患者中ENTA和BAL的比较应在进一步的试验中进行研究.
方法：对每天两次静脉注射600mg利奈唑胺的插管ICU患者进行稳态检查。首先,在6例患者中进行了初步实验，以研究哪些患者适合在ENTA中进行利奈唑胺测量。第二步,在9例合适的患者中测定了利奈唑胺的血浆和ENTA的谷和峰浓度.
结果：利奈唑胺可以在具有粘性质地和>0.5mL体积的ENTA中有效检测到。平均（SD）利奈唑胺谷浓度在血浆中为2.02（1.27）mg/L，在ENTA中为1.60（1.36）mg/L，导致肺穿透率中位数为104％。血浆和ENTA的平均（SD）峰浓度为10.77（5.93）和4.74（2.66）mg/L。
结论：利奈唑胺可以在具有足够质地和体积的ENTA中有效测定。渗透率与已经公布的BAL浓度相当。这种方法可能为感染部位“肺”的TDM提供一种简单而非侵入性的方法。由于可行性研究的有希望的结果，同一患者中ENTA和BAL的比较应在进一步的试验中进行研究.
