L. Spallanzani, National Institute for Infectious Diseases Rome, Italy.
Minerva Anestesiol. 2010 Jul;76(7):509-24.
Infections, particularly those caused by resistant pathogens, are a common cause of morbidity and mortality in critically ill patients. However, the availability of effective antimicrobial agents is limited. Critical illness itself can influence the pharmacokinetic/pharmacodynamic (PK/PD) parameters of antimicrobials by altering their volume of distribution and the rate of their excretion and elimination and by impairing their penetration into tissues. Therefore, when designing a treatment regimen, the intensivist should consider and take advantage of antibiotic PK/PD properties. There is significant but inconclusive evidence that critically ill patients may benefit more when antibiotics with time-dependent action are administered in a continuous/prolonged infusion regimen. On the other hand, aminoglycosides exhibit a concentration-dependent pattern of killing and should be administered at high doses once daily or at extended intervals, and their levels in the plasma should by strictly monitored to avoid both underexposure and toxicity. The problem of antimicrobial resistance now involves agents traditionally considered reliable in that aspect, such as vancomycin. Strict monitoring of vancomycin MIC for methicillin-resistant Staphylococcus aureus and the prudent use of the available alternative agents as well as de-escalation strategies might be reasonable strategies for dealing with this problem.
感染，特别是由耐药病原体引起的感染，是重症患者发病率和死亡率的常见原因。然而，有效的抗菌药物的供应是有限的。重症本身可以通过改变抗菌药物的分布容积和排泄消除率，以及削弱其对组织的穿透性，来影响抗菌药物的药代动力学/药效学（PK/PD）参数。因此，在设计治疗方案时，重症医师应考虑并利用抗生素的 PK/PD 特性。有大量但尚无定论的证据表明，当具有时间依赖性作用的抗生素以持续/延长输注方案给药时，重症患者可能会从中获益更多。另一方面，氨基糖苷类药物表现出浓度依赖性杀菌模式，应每日一次或延长时间间隔给予高剂量，并严格监测其在血浆中的水平，以避免药物暴露不足和毒性。现在，抗生素耐药性问题涉及到传统上在这方面被认为可靠的药物，如万古霉素。严格监测耐甲氧西林金黄色葡萄球菌的万古霉素 MIC，并谨慎使用现有替代药物以及降阶梯策略，可能是应对这一问题的合理策略。
