Alshaer Mohammad H, Maranchick Nicole F, Maguigan Kelly L, Shoulders Bethany R, Mousa Mays J, Murray Melissa, Ashton Jennifer, Alexander Kaitlin, Santevecchi Barbara A, DeSear Kathryn, Venugopalan Veena, Cherabuddi Kartikeya, Peloquin Charles A
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA.
Antibiotics (Basel). 2025 May 1;14(5):463. doi: 10.3390/antibiotics14050463.
To assess the impact of beta-lactam therapeutic drug monitoring (TDM) timing and therapy adjustment on clinical cure and 30-day mortality. This was a prospective study of critically ill patients admitted to the University of Florida Health Shands Hospital intensive care unit (ICU) between 2021 and 2022, ≥18 years old, and requiring beta-lactam therapy for a suspected or confirmed infection. Beta-lactam concentrations were measured per standard of care, pharmacokinetic/dynamic (PK/PD) target attainment was calculated, and therapy was adjusted if needed. Multiple regression and time-to-event (TTE) analyses were performed. A total of 297 infection episodes from 268 patients were included. The mean (SD) age was 56 years (17), weight was 82 kg (32), and 14% received renal replacement therapy. The most common infection source was the lung, and the most common beta-lactam was cefepime. The most common infusion duration was 30 min. The median (IQR) time to first TDM was 2.7 days (1.7-4.7). Fifty-seven percent of patients required therapy adjustment. Increases in beta-lactam dose, frequency, or infusion duration were associated with lower 30-day mortality compared to continuing the same regimen (aOR 0.30, = 0.015). Delay in performing TDM was associated with lower probability of clinical cure (aOR 0.92, = 0.0023). Patients who had the regimen increased had shorter hospital stay compared to those who had it decreased. Timing of beta-lactam TDM in ICU patients was a significant predictor of clinical cure, while adjusting beta-lactam therapy to achieve higher exposure was a significant predictor of 30-day mortality.
评估β-内酰胺类药物治疗药物监测（TDM）时机及治疗调整对临床治愈和30天死亡率的影响。这是一项对2021年至2022年间入住佛罗里达大学健康珊兹医院重症监护病房（ICU）、年龄≥18岁且因疑似或确诊感染需要接受β-内酰胺类治疗的重症患者进行的前瞻性研究。按照标准治疗流程测量β-内酰胺类药物浓度，计算药代动力学/药效学（PK/PD）目标达成情况，并在需要时调整治疗方案。进行了多元回归分析和事件发生时间（TTE）分析。共纳入268例患者的297次感染发作。平均（标准差）年龄为56岁（17岁），体重为82千克（32千克），14%的患者接受了肾脏替代治疗。最常见的感染源是肺部，最常用的β-内酰胺类药物是头孢吡肟。最常见的输注持续时间为30分钟。首次TDM的中位（四分位间距）时间为2.7天（1.7 - 4.7天）。57%的患者需要调整治疗方案。与继续相同治疗方案相比，增加β-内酰胺类药物剂量、给药频率或输注持续时间与较低的30天死亡率相关（校正比值比0.30，P = 0.015）。延迟进行TDM与临床治愈概率较低相关（校正比值比0.92，P = 0.0023）。治疗方案增加的患者与治疗方案减少的患者相比，住院时间更短。ICU患者β-内酰胺类TDM的时机是临床治愈的重要预测因素，而调整β-内酰胺类治疗以实现更高的药物暴露是30天死亡率的重要预测因素。
