Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Clin Infect Dis. 2023 Jul 26;77(2):242-251. doi: 10.1093/cid/ciad168.
In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs).
Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated.
A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics.
For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.
在 POET（部分口服心内膜炎治疗）试验中，口服降阶梯治疗与全疗程静脉用抗生素治疗相比不劣效。本研究的目的是进行口服治疗感染性心内膜炎的药代动力学/药效学分析，以评估目标浓度达标率（PTAs）。
在第 1 天和第 5 天测量口服抗生素的血浆浓度。测定引起感染性心内膜炎的细菌（链球菌、葡萄球菌或肠球菌）的最小抑菌浓度（MIC）。根据文献，使用 MIC 以上时间或曲线下面积与 MIC 的比值，预先设定药代动力学/药效学目标。对阿莫西林、双氯西林、利奈唑胺、莫西沙星和利福平进行群体药代动力学建模和药代动力学/药效学分析，并计算达标率。
共有 236 例患者参与了这项 POET 子研究。阿莫西林和利奈唑胺的达标率为 88%-100%。莫西沙星和利福平的达标率为 71%-100%。对于葡萄球菌，使用临床折点时，双氯西林的达标率为 9%-17%。第 1 天有 74 例患者和第 5 天有 65 例患者获得了 2 种口服抗生素的药代动力学和 MIC 数据。其中，第 1 天有 13 例患者和第 5 天有 14 例患者仅达到 1 种抗生素的目标。1 例患者未达到 2 种抗生素中的任何一种的目标。
对于单独使用的口服抗生素，大多数达到了目标水平。对于未达到目标水平的患者，通过使用 2 种不同的抗生素进行补偿。这些发现支持感染性心内膜炎患者口服降阶梯抗生素治疗的疗效。
