Intravenous administration of antibiotics is recommended during the early phase of methicillin-susceptible S. aureus (MSSA) bone and joint infection (BJI). We sought to compare the plasma concentrations of cloxacillin administered alternately by continuous and intermittent infusion (CI and ItI) in patients with MSSA BJI. In this prospective crossover trial, patients were randomly assigned to receive either 3 days of CI (two 75-mg/kg 12-h cloxacillin infusions per day) and then 3 days of ItI (four 37.5-mg/kg 1-h cloxacillin infusions per day) or vice versa. The drug concentration measurement was performed on day 3 of each type of administration at 1, 6, and 11 h and at 1, 2, 3, 4, and 6 h after the beginning of CI and ItI, respectively. We used the nonparametric algorithm NPAG to estimate population pharmacokinetic (PK) parameters. The final model was used to perform pharmacokinetic/pharmacodynamic (PK/PD) simulations and calculate the probabilities of target attainment (PTA) for several ItI and CI dosing regimens. We considered two PK/PD targets of time spent above the MIC for free cloxacillin concentrations (fT_>MIC): 50 and 100%. Eighty-four concentrations from 11 patients were analyzed. A two-compartment model adequately described the data. ItI with q6h regimens and short 1-h infusions of 2,000 or 3,000 mg were associated with low PTA, even for the low target (50% fT_>MIC) while 3-h infusions and continuous infusions (6 to 12 g/day) were associated with a PTA of >90% for an MIC up to 0.5 mg/liter. These results support the use of prolonged or continuous infusion of cloxacillin in patients with BJI.

中文翻译：

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金黄色葡萄球菌骨及关节感染期间持续输注氯西林的人群药代动力学分析

建议在对甲氧西林敏感的金黄色葡萄球菌的早期静脉内施用抗生素（MSSA）骨骼和关节感染（BJI）。我们试图比较连续和间歇输注（CI和ItI）对MSSA BJI患者交替使用的氯唑西林的血浆浓度。在这项前瞻性交叉试验中，患者被随机分配为接受3天CI（每天两次75 mg / kg的12小时克洛西林输注），然后接受3天ItI（四个37.5 mg / kg的1小时氯西林输注）。每天），反之亦然。在每种给药类型的第3天分别在CI和ItI开始后的1、6、11小时和1、2、3、4和6小时进行药物浓度测量。我们使用非参数算法NPAG估算群体药代动力学（PK）参数。最终模型用于执行药代动力学/药效学（PK / PD）模拟，并计算几种ItI和CI给药方案的目标达成率（PTA）。我们考虑了在MIC上方花费的两个PK / PD目标时间，以达到自由氯氧西林浓度（fT _{> MIC}）：50和100％。分析了11位患者的84种浓度。两室模型充分描述了数据。即使采用低靶点（50％fT _{> MIC}）的低剂量PTA，qI方案和q6h方案且短时间的1h输注2,000或3,000 mg也与3h输注和连续输注（6至12 g /天）有关。对于高达0.5 mg / L的MIC，PTA> 90％的情况。这些结果支持在BJI患者中长期或持续输注氯西林。