Clinic of Infectious Diseases, "Sf. Parascheva" Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania.
Department of Infectious Diseases, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 16 Universitatii Street, 700115 Iasi, Romania.
Medicina (Kaunas). 2023 Feb 28;59(3):478. doi: 10.3390/medicina59030478.
Optimizing the entire therapeutic regimen in septic critically ill patients should be based not only on improving antibiotic use but also on optimizing the entire therapeutic regimen by considering possible drug-drug or drug-nutrient interactions. The aim of this narrative review is to provide a comprehensive overview on recent advances to optimize the therapeutic regimen in septic critically ill patients based on a pharmacokinetics and pharmacodynamic approach. Studies on recent advances on TDM-guided drug therapy optimization based on PK and/or PD results were included. Studies on patients <18 years old or with classical TDM-guided therapy were excluded. New approaches in TDM-guided therapy in septic critically ill patients based on PK and/or PD parameters are presented for cefiderocol, carbapenems, combinations beta-lactams/beta-lactamase inhibitors (piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam), plazomicin, oxazolidinones and polymyxins. Increased midazolam toxicity in combination with fluconazole, nephrotoxic synergism between furosemide and aminoglycosides, life-threatening hypoglycemia after fluoroquinolone and insulin, prolonged muscle weakness and/or paralysis after neuromuscular blocking agents and high-dose corticosteroids combinations are of interest in critically ill patients. In the real-world practice, the use of probiotics with antibiotics is common; even data about the risk and benefits of probiotics are currently spares and inconclusive. According to current legislation, probiotic use does not require safety monitoring, but there are reports of endocarditis, meningitis, peritonitis, or pneumonia associated with probiotics in critically ill patients. In addition, probiotics are associated with risk of the spread of antimicrobial resistance. The TDM-guided method ensures a true optimization of antibiotic therapy, and particular efforts should be applied globally. In addition, multidrug and drug-nutrient interactions in critically ill patients may increase the likelihood of adverse events and risk of death; therefore, the PK and PD particularities of the critically ill patient require a multidisciplinary approach in which knowledge of clinical pharmacology is essential.
优化脓毒症危重症患者的整个治疗方案不仅应基于改善抗生素的使用，还应通过考虑可能的药物-药物或药物-营养素相互作用来优化整个治疗方案。本综述的目的是提供一个全面的概述，介绍基于药代动力学和药效学方法优化脓毒症危重症患者治疗方案的最新进展。纳入了基于 PK 和/或 PD 结果进行 TDM 指导药物治疗优化的研究。排除了年龄<18 岁或接受经典 TDM 指导治疗的患者的研究。提出了基于 PK 和/或 PD 参数的新方法，用于优化脓毒症危重症患者的 TDM 指导治疗，包括头孢地尔、碳青霉烯类药物、β-内酰胺/β-内酰胺酶抑制剂（哌拉西林/他唑巴坦、头孢他啶/阿维巴坦、头孢唑肟/阿维巴坦）联合治疗、硫酸黏菌素、恶唑烷酮类药物和多黏菌素。氟康唑联合咪达唑仑时毒性增加、呋塞米和氨基糖苷类药物肾毒性协同作用、氟喹诺酮类药物和胰岛素合用致危及生命的低血糖、神经肌肉阻滞剂和大剂量皮质类固醇联合使用后肌肉无力和/或瘫痪时间延长，这些都是危重症患者关注的问题。在实际临床实践中，抗生素联合使用益生菌很常见；甚至关于益生菌的风险和益处的数据目前也很少且不确定。根据现行法规，益生菌的使用不需要进行安全性监测，但有报道称益生菌在危重症患者中可引起心内膜炎、脑膜炎、腹膜炎或肺炎。此外，益生菌与抗菌药物耐药性的传播有关。TDM 指导方法可确保抗生素治疗的真正优化，应在全球范围内进行。此外，危重症患者的多药物和药物-营养素相互作用可能会增加不良事件的发生和死亡的风险；因此，危重症患者的 PK 和 PD 特点需要多学科方法，临床药理学知识至关重要。
