成人脓毒症患者β-内酰胺类抗生素延长输注专家共识

doi:10.3877/cma.j.issn.2096-1537.2024.04.001

脓毒症是宿主对感染的异常反应所引起的危及生命的器官功能障碍综合征，早期和恰当的抗感染治疗可以改善其预后。β-内酰胺类抗生素是治疗脓毒症的常用抗感染药物。β-内酰胺类抗生素延长输注时间是一种简便有效的优化药物PK/PD，提高药物治疗效果的方法。本共识就成人脓毒症患者β-内酰胺类抗生素延长输注时间的基础理论、有效性、安全性及临床使用要点展开讨论，总结现有的循证医学证据，以供临床实践参考。

关键词: 脓毒症, β-内酰胺类抗生素, 延长输注, 持续输注

Sepsis is a pathologic syndrome of life-threatening organ dysfunction caused by a dysregulated host immune response to infection. Early and appropriate anti-infection treatment can improve the prognosis. β-lactam antibiotics are common antibiotics for the treatment of sepsis. Extended infusion of β-lactam antibiotics is a simple and effective method to optimize pharmacokinetic/pharmacodynamics and improve the efficiency. In the experts consensus, we discuss the basic theory, efficiency, safety, and clinical application on extended infusion of β-lactam antibiotics in adult sepsis patients, and summarize the evidence-based medicine for reference.

Key words: Sepsis, β-lactam antibiotics, Extended infusion, Continuous infusion

图1 β-内酰胺类抗生素不同输注方式的血药浓度-时间曲线

表1 常用β-内酰胺类抗生素延长输注时间用法举例及溶液稳定性

药品名	说明书用法	临床研究用法举例	说明书稳定性
哌拉西林他唑巴坦	须缓慢静脉滴注给药（如，给药时间20~30 min以上）	4.5 g/次，每8~12 h 1次，每次维持4 h（EI）^[50]； 4.5 g负荷剂量后3.375 g/次，每6 h 1次，每次维持3 h（EI）^[23]； 2.25 g负荷剂量后9 g/d，维持输注（CI）^[18]	室温（20~25℃）24 h；冷藏（2~8℃）48 h
头孢吡肟	约30 min滴注完毕	2 g/次，每8 h 1次，每次维持3 h（EI）^[51]； 2 g/次，每8 h 1次，每次维持4 h（EI）或6 g/d（CI）^[52]	未提及
头孢他啶	无说明	6 g/d CI^[46]； 2 g负荷剂量后2~6 g/d（CI）^[53]	2~8℃冷藏可存放24 h
美罗培南	15~30 min内完成给药	每剂250 mg推注，然后750 mg维持3 h，每8 h 1次（EI）^[54]； 1 g/次，每8 h 1次，每次维持4 h^[16]； 0.5 g负荷剂量维持30 min，3 g/d（CI）^[55]； 3~6 g/d（CI），或2 g/次，每8 h 1次，每次维持4 h（EI）^[56]	室温下应于6 h内使用
亚胺培南/西司他丁	500 mg静脉输注，持续20~30 min； 1000 mg静脉输注，持续40~60 min	1 g/次，每6 h 1次，每次维持4 h（EI）^[57]	室温（25℃）4 h；冷藏（4℃）24 h
比阿培南	0.3 g滴注30~60 min	0.3 g/次，每6 h 1次，每次维持3 h（EI），或1.2 g/d（CI）^[37]； 0.6 g/次，每12 h 1次，每次维持2~4 h（EI）^[57]； 0.3~0.6 g/次，每6~12 h 1次，每次维持2~4 h（EI）^[58,59,60]	室温6 h；冷藏（8℃）24 h
厄他培南	常用剂量为1 g，输注时间应超过30 min	1 g/次，1次/d，每次维持0.5 h（EI）^[61]； 1 g/次，1次/d，每次维持1 h（EI）^[62]	室温（25℃）6 h；冰箱（5℃）中贮存24 h，并在移出冰箱后4 h内使用
头孢哌酮/舒巴坦	静脉滴注时间应至少为15~60 min	3 g/次，每8 h 1次，每次维持3 h（EI）；或9 g/d（CI）^[31,62]；	未提及
头孢他啶/阿维巴坦	输注时间2 h	2.5 g/次，每8 h 1次，每次维持4 h（EI）^[63]； 2.5 g/次，每8 h 1次，每次维持3 h（EI）^[64]； 10 g/d（CI）^[65]	已证实在2~8℃中24 h及后续在25℃以下12 h内的化学和物理稳定性；从微生物学角度考虑，2~8℃下保存时间不应超过24 h
氨曲南	滴注时间20~60 min	2 g/次，每6 h 1次，每次维持4 h（EI）^[66]； 2 g/次，每8 h 1次，每次维持2 h（EI）；或2 g负荷剂量维持2 h，然后8 g/d（CI）^[55]	未提及

表1 常用β-内酰胺类抗生素延长输注时间用法举例及溶液稳定性

药品名	说明书用法	临床研究用法举例	说明书稳定性
哌拉西林他唑巴坦	须缓慢静脉滴注给药（如，给药时间20~30 min以上）	4.5 g/次，每8~12 h 1次，每次维持4 h（EI）^[50]； 4.5 g负荷剂量后3.375 g/次，每6 h 1次，每次维持3 h（EI）^[23]； 2.25 g负荷剂量后9 g/d，维持输注（CI）^[18]	室温（20~25℃）24 h；冷藏（2~8℃）48 h
头孢吡肟	约30 min滴注完毕	2 g/次，每8 h 1次，每次维持3 h（EI）^[51]； 2 g/次，每8 h 1次，每次维持4 h（EI）或6 g/d（CI）^[52]	未提及
头孢他啶	无说明	6 g/d CI^[46]； 2 g负荷剂量后2~6 g/d（CI）^[53]	2~8℃冷藏可存放24 h
美罗培南	15~30 min内完成给药	每剂250 mg推注，然后750 mg维持3 h，每8 h 1次（EI）^[54]； 1 g/次，每8 h 1次，每次维持4 h^[16]； 0.5 g负荷剂量维持30 min，3 g/d（CI）^[55]； 3~6 g/d（CI），或2 g/次，每8 h 1次，每次维持4 h（EI）^[56]	室温下应于6 h内使用
亚胺培南/西司他丁	500 mg静脉输注，持续20~30 min； 1000 mg静脉输注，持续40~60 min	1 g/次，每6 h 1次，每次维持4 h（EI）^[57]	室温（25℃）4 h；冷藏（4℃）24 h
比阿培南	0.3 g滴注30~60 min	0.3 g/次，每6 h 1次，每次维持3 h（EI），或1.2 g/d（CI）^[37]； 0.6 g/次，每12 h 1次，每次维持2~4 h（EI）^[57]； 0.3~0.6 g/次，每6~12 h 1次，每次维持2~4 h（EI）^[58,59,60]	室温6 h；冷藏（8℃）24 h
厄他培南	常用剂量为1 g，输注时间应超过30 min	1 g/次，1次/d，每次维持0.5 h（EI）^[61]； 1 g/次，1次/d，每次维持1 h（EI）^[62]	室温（25℃）6 h；冰箱（5℃）中贮存24 h，并在移出冰箱后4 h内使用
头孢哌酮/舒巴坦	静脉滴注时间应至少为15~60 min	3 g/次，每8 h 1次，每次维持3 h（EI）；或9 g/d（CI）^[31,62]；	未提及
头孢他啶/阿维巴坦	输注时间2 h	2.5 g/次，每8 h 1次，每次维持4 h（EI）^[63]； 2.5 g/次，每8 h 1次，每次维持3 h（EI）^[64]； 10 g/d（CI）^[65]	已证实在2~8℃中24 h及后续在25℃以下12 h内的化学和物理稳定性；从微生物学角度考虑，2~8℃下保存时间不应超过24 h
氨曲南	滴注时间20~60 min	2 g/次，每6 h 1次，每次维持4 h（EI）^[66]； 2 g/次，每8 h 1次，每次维持2 h（EI）；或2 g负荷剂量维持2 h，然后8 g/d（CI）^[55]	未提及

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Experts consensus on extended infusion of β-lactam antibiotics in adult sepsis patients

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Experts consensus on extended infusion of β-lactam antibiotics in adult sepsis patients