Infectious Disease Pharmacokinetics Laboratory College of Pharmacy, and Emerging Pathogens Institute, University of Florida, Gainesville, USA.
Department of Surgery, University of Florida College of Medicine, Gainesville, USA.
J Burn Care Res. 2023 Jan 5;44(1):121-128. doi: 10.1093/jbcr/irac099.
Thermal injuries alter pharmacokinetics, complicating the prediction of standard antibiotic dose effectiveness. Therapeutic drug monitoring (TDM) has been proposed to prevent subtherapeutic dosing of antibiotic therapy, but remains scarcely studied in the burn patient population. A retrospective chart review of burn patients receiving beta-lactam TDM from 2016 to 2019 was conducted. Adult patients with thermal injury receiving cefepime, piperacillin/tazobactam, or meropenem for ≥48 hours were included. Between February 2016 and July 2017, we utilized selective TDM based on clinical judgement to guide treatment. From October 2018 until July 2019, TDM was expanded to all burn patients on beta-lactams. The primary endpoint was achievement of therapeutic concentration, and the secondary endpoints were clinical cure, culture clearance, new resistance, length of stay, and mortality. The selective (control) group included 19 patients and the universal (study) group reviewed 23 patients. In both groups, skin and lungs were the most common primary infection sources, with Pseudomonas aeruginosa as the most common species. In the universal cohort, patients were older with higher risk factors, but more frequently achieved the target drug concentration, required less days to start TDM (p < .0001), and had more frequent measurements and beta-lactam dose adjustments. Positive clinical outcome was reported in 77%, and microbial eradication in 82% of all patients. All clinical outcomes were similar between the groups. The implementation of beta-lactam TDM protocol shortened the time, increased the probability of appropriate target attainment, and individualized beta-lactam therapy in burn patients.
热损伤改变了药代动力学，使标准抗生素剂量效果的预测变得复杂。治疗药物监测（TDM）已被提议用于预防抗生素治疗的治疗剂量不足，但在烧伤患者人群中研究甚少。对 2016 年至 2019 年接受β-内酰胺类 TDM 的烧伤患者进行了回顾性图表审查。纳入接受头孢吡肟、哌拉西林/他唑巴坦或美罗培南治疗≥48 小时的成人热损伤患者。2016 年 2 月至 2017 年 7 月，我们根据临床判断利用选择性 TDM 来指导治疗。从 2018 年 10 月至 2019 年 7 月，TDM 扩大到所有接受β-内酰胺类药物治疗的烧伤患者。主要终点是达到治疗浓度，次要终点是临床治愈、培养清除、新出现的耐药性、住院时间和死亡率。选择性（对照）组包括 19 例患者，回顾性研究了 23 例患者。在两组中，皮肤和肺部是最常见的原发性感染源，铜绿假单胞菌是最常见的菌种。在普遍性队列中，患者年龄较大，危险因素较高，但更频繁地达到目标药物浓度，开始 TDM 的天数更少（p<0.0001），并且更频繁地进行测量和β-内酰胺剂量调整。所有患者中有 77%报告了阳性临床结果，82%的患者微生物清除。两组间所有临床结果均相似。β-内酰胺 TDM 方案的实施缩短了时间，增加了适当目标实现的可能性，并使烧伤患者的β-内酰胺个体化治疗。
