Service of Intensive Care Medicine, Parc de Salut Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
Drugs. 2012 Mar 5;72(4):447-70. doi: 10.2165/11599520-000000000-00000.
Critically ill patients admitted to the intensive care unit (ICU) are frequently treated with antimicrobials. The appropriate and judicious use of antimicrobial treatment in the ICU setting is a constant clinical challenge for healthcare staff due to the appearance and spread of new multiresistant pathogens and the need to update knowledge of factors involved in the selection of multiresistance and in the patient's clinical response. In order to optimize the efficacy of empirical antibacterial treatments and to reduce the selection of multiresistant pathogens, different strategies have been advocated, including de-escalation therapy and pre-emptive therapy as well as measurement of pharmacokinetic and pharmacodynamic (pK/pD) parameters for proper dosing adjustment. Although the theoretical arguments of all these strategies are very attractive, evidence of their effectiveness is scarce. The identification of the concentration-dependent and time-dependent activity pattern of antimicrobials allow the classification of drugs into three groups, each group with its own pK/pD characteristics, which are the basis for the identification of new forms of administration of antimicrobials to optimize their efficacy (single dose, loading dose, continuous infusion) and to decrease toxicity. The appearance of new multiresistant pathogens, such as imipenem-resistant Pseudomonas aeruginosa and/or Acinetobacter baumannii, carbapenem-resistant Gram-negative bacteria harbouring carbapenemases, and vancomycin-resistant Enterococcus spp., has determined the use of new antibacterials, the reintroduction of other drugs that have been removed in the past due to toxicity or the use of combinations with in vitro synergy. Finally, pharmacoeconomic aspects should be considered for the choice of appropriate antimicrobials in the care of critically ill patients.
重症监护病房(ICU)收治的危重症患者常需使用抗菌药物。由于新的多耐药病原体的出现和传播,以及需要更新与耐药选择和患者临床反应相关的知识,医护人员在 ICU 环境中对抗菌药物治疗的合理应用面临持续的临床挑战。为了优化经验性抗菌治疗的疗效并减少多耐药病原体的选择,已提倡采用不同的策略,包括降阶梯治疗和抢先治疗,以及测量药代动力学和药效学(PK/PD)参数以进行适当的剂量调整。尽管所有这些策略的理论观点都非常有吸引力,但缺乏其有效性的证据。抗菌药物浓度依赖性和时间依赖性活性模式的确定,可将药物分为三组,每组具有其自身的 PK/PD 特征,这是确定新的抗菌药物给药方式以优化疗效(单剂量、负荷剂量、持续输注)和降低毒性的基础。耐碳青霉烯类铜绿假单胞菌和/或鲍曼不动杆菌、产碳青霉烯酶的耐碳青霉烯类革兰阴性菌等新的多耐药病原体的出现,已决定了新型抗菌药物的使用、过去因毒性而被淘汰的其他药物的重新引入,或与体外协同作用的联合用药。最后,在危重症患者的治疗中,应考虑药物经济学方面以选择合适的抗菌药物。