Morales Junior Ronaldo, Pereira Gabriela Otofuji, Tiguman Gustavo Magno Baldin, Juodinis Vanessa D'Amaro, Telles João Paulo, de Souza Daniela Carla, Santos Silvia Regina Cavani Jorge
Clinical Pharmacokinetics Center, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Pediatric Intensive Care Unit, Department of Pediatrics, Hospital Sírio-Libanês, São Paulo, Brazil.
Front Pediatr. 2022 Mar 10;10:777854. doi: 10.3389/fped.2022.777854. eCollection 2022.
The antimicrobial therapy of sepsis and septic shock should be individualized based on pharmacokinetic/pharmacodynamic (PK/PD) parameters to deliver effective and timely treatment of life-threatening infections. We conducted a literature scoping review to identify therapeutic targets of beta-lactam antibiotics in septic pediatric patients and the strategies that have been applied to overcome sepsis-related altered pharmacokinetics and increase target attainment against susceptible pathogens. A systematic search was conducted in the MEDLINE, EMBASE and Web of Science databases to select studies conducted since 2010 with therapeutic monitoring data of beta-lactams in septic children. Last searches were performed on 02 September 2021. Two independent authors selected the studies and extracted the data. A narrative and qualitative approach was used to summarize the findings. Out of the 118 identified articles, 21 met the eligibility criteria. Population pharmacokinetic modeling was performed in 12 studies, while nine studies reported data from bedside monitoring of beta-lactams. Most studies were conducted in the United States of America ( = 9) and France ( = 5) and reported PK/PD data of amoxicillin, ampicillin, azlocillin, aztreonam, cefazolin, cefepime, cefotaxime, ceftaroline, ceftazidime, doripenem, meropenem and piperacillin/tazobactam. Therapeutic targets ranged from to 40% T> MIC to 100% T> 6 × MIC. Prolonging the infusion time and frequency were most described strategies to increase target attainment. Monitoring beta-lactam serum concentrations in clinical practice may potentially maximize therapeutic target attainment. Further studies are required to define the therapeutic target associated with the best clinical outcomes.
脓毒症和脓毒性休克的抗菌治疗应根据药代动力学/药效学(PK/PD)参数进行个体化,以便对危及生命的感染进行有效且及时的治疗。我们进行了一项文献综述,以确定脓毒症患儿中β-内酰胺类抗生素的治疗靶点,以及为克服脓毒症相关的药代动力学改变和提高对易感病原体的靶点达成率而应用的策略。在MEDLINE、EMBASE和科学网数据库中进行了系统检索,以选择自2010年以来有关脓毒症患儿β-内酰胺类药物治疗监测数据的研究。最后一次检索于2021年9月2日进行。两名独立作者选择了研究并提取了数据。采用叙述性和定性方法总结研究结果。在118篇已识别的文章中,21篇符合纳入标准。12项研究进行了群体药代动力学建模,而9项研究报告了β-内酰胺类药物床边监测的数据。大多数研究在美国(n = 9)和法国(n = 5)进行,报告了阿莫西林、氨苄西林、阿洛西林、氨曲南、头孢唑林、头孢吡肟、头孢噻肟、头孢托罗、头孢他啶、多利培南、美罗培南和哌拉西林/他唑巴坦的PK/PD数据。治疗靶点范围从40%T>MIC到100%T>6×MIC。延长输注时间和频率是最常描述的提高靶点达成率的策略。在临床实践中监测β-内酰胺类药物的血清浓度可能会使治疗靶点达成率最大化。需要进一步研究来确定与最佳临床结果相关的治疗靶点。