Weinelt Ferdinand Anton, Stegemann Miriam Songa, Theloe Anja, Pfäfflin Frieder, Achterberg Stephan, Weber Franz, Dübel Lucas, Mikolajewska Agata, Uhrig Alexander, Kiessling Peggy, Huisinga Wilhelm, Michelet Robin, Hennig Stefanie, Kloft Charlotte
Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Kelchstr. 31, 12169 Berlin, Germany.
Graduate Research Training Program PharMetrX, Freie Universitaet Berlin/Universität Potsdam, 12169 Berlin, Germany.
Antibiotics (Basel). 2022 Jun 2;11(6):758. doi: 10.3390/antibiotics11060758.
The drug concentrations targeted in meropenem and piperacillin/tazobactam therapy also depend on the susceptibility of the pathogen. Yet, the pathogen is often unknown, and antibiotic therapy is guided by empirical targets. To reliably achieve the targeted concentrations, dosing needs to be adjusted for renal function. We aimed to evaluate a meropenem and piperacillin/tazobactam monitoring program in intensive care unit (ICU) patients by assessing (i) the adequacy of locally selected empirical targets, (ii) if dosing is adequately adjusted for renal function and individual target, and (iii) if dosing is adjusted in target attainment (TA) failure. In a prospective, observational clinical trial of drug concentrations, relevant patient characteristics and microbiological data (pathogen, minimum inhibitory concentration (MIC)) for patients receiving meropenem or piperacillin/tazobactam treatment were collected. If the MIC value was available, a target range of 1-5 × MIC was selected for minimum drug concentrations of both drugs. If the MIC value was not available, 8-40 mg/L and 16-80 mg/L were selected as empirical target ranges for meropenem and piperacillin, respectively. A total of 356 meropenem and 216 piperacillin samples were collected from 108 and 96 ICU patients, respectively. The vast majority of observed MIC values was lower than the empirical target (meropenem: 90.0%, piperacillin: 93.9%), suggesting empirical target value reductions. TA was found to be low (meropenem: 35.7%, piperacillin 50.5%) with the lowest TA for severely impaired renal function (meropenem: 13.9%, piperacillin: 29.2%), and observed drug concentrations did not significantly differ between patients with different targets, indicating dosing was not adequately adjusted for renal function or target. Dosing adjustments were rare for both drugs (meropenem: 6.13%, piperacillin: 4.78%) and for meropenem irrespective of TA, revealing that concentration monitoring alone was insufficient to guide dosing adjustment. Empirical targets should regularly be assessed and adjusted based on local susceptibility data. To improve TA, scientific knowledge should be translated into easy-to-use dosing strategies guiding antibiotic dosing.
美罗培南和哌拉西林/他唑巴坦治疗的目标药物浓度也取决于病原体的敏感性。然而，病原体往往未知，抗生素治疗以经验性目标为指导。为可靠地达到目标浓度，给药需根据肾功能进行调整。我们旨在通过评估（i）当地选择的经验性目标是否合适，（ii）给药是否根据肾功能和个体目标进行了充分调整，以及（iii）在目标达成（TA）失败时是否调整给药，来评估重症监护病房（ICU）患者的美罗培南和哌拉西林/他唑巴坦监测方案。在一项关于药物浓度的前瞻性观察性临床试验中，收集了接受美罗培南或哌拉西林/他唑巴坦治疗患者的相关患者特征和微生物学数据（病原体、最低抑菌浓度（MIC））。如果有MIC值，两种药物的最低药物浓度选择1 - 5×MIC的目标范围。如果没有MIC值，美罗培南和哌拉西林的经验性目标范围分别选择8 - 40mg/L和16 - 80mg/L。分别从108例和96例ICU患者中收集了356份美罗培南和216份哌拉西林样本。绝大多数观察到的MIC值低于经验性目标（美罗培南：90.0%，哌拉西林：93.9%），提示经验性目标值可降低。发现TA较低（美罗培南：35.7%，哌拉西林50.5%），肾功能严重受损时TA最低（美罗培南：13.9%，哌拉西林：29.2%），不同目标患者的观察药物浓度无显著差异，表明给药未根据肾功能或目标进行充分调整。两种药物的给药调整都很少见（美罗培南：6.13%，哌拉西林：4.78%），且美罗培南无论TA情况如何调整都很少，这表明仅浓度监测不足以指导给药调整。应根据当地敏感性数据定期评估和调整经验性目标。为提高TA，应将科学知识转化为易于使用的给药策略以指导抗生素给药。
