Nobre Vandack, Harbarth Stephan, Graf Jean-Daniel, Rohner Peter, Pugin Jérôme
Intensive Care, University Hospital of Geneva, 24, Micheli-du-Crest, 1211 Geneva 14, Switzerland.
Am J Respir Crit Care Med. 2008 Mar 1;177(5):498-505. doi: 10.1164/rccm.200708-1238OC. Epub 2007 Dec 20.
The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance.
To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock.
In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules.
Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03).
Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm.
脓毒症重症患者的抗生素治疗疗程可能导致抗生素过度使用，增加产生细菌耐药性的风险。
检验以下假设，即与经验性规则相比，基于降钙素原（PCT）系列测量的算法可缩短抗生素治疗疗程，且不会导致严重脓毒症和脓毒性休克患者出现更多不良结局。
随机分配至干预组的患者，当PCT水平较初始值下降90%或更多时（若临床医生同意）停用抗生素，但在第3天之前（若基线PCT水平<1μg/L）或第5天之前（若基线PCT水平≥1μg/L）不停用。对照组患者中，临床医生根据经验性规则决定抗生素治疗疗程。
分配至PCT组的患者首次感染时抗生素治疗的中位疗程比对照组短3.5天（意向性分析，n = 79，P = 0.15）。在可根据PCT系列测量做出决策的患者中，PCT指导使抗生素治疗疗程缩短了4天（符合方案分析，n = 68，P = 0.003），且总体抗生素暴露量更小（P = 0.0002）。PCT组和对照组的主要感染死亡率和复发率相似。分配至PCT组的患者重症监护病房住院时间也短2天（P = 0.03）。
我们的结果表明，基于PCT系列测量的方案可缩短严重脓毒症和脓毒性休克患者的抗生素治疗疗程及暴露量，且无明显危害。
