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

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

Abstract

Abstract:

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

Force on Experts Consensus on Extended Infusion of β-Lactam Task. Experts consensus on extended infusion of β-lactam antibiotics in adult sepsis patients[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(04): 313-324.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://icu.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2096-1537.2024.04.001

https://icu.cma-cmc.com.cn/EN/Y2024/V10/I04/313

Figures/Tables 2

References 109

1	Rhodes A, Evans LE, Alhazzani W, et al.Surviving sepsis campaign:international guidelines for management of sepsis and septic shock:2016 [J].Intensive Care Med, 2017, 43(3): 304-377.
2	Bycroft BW, Shute RE.The molecular basis for the mode of action of Beta-lactam antibiotics and mechanisms of resistance [J].Pharm Res,1985, 2(1): 3-14.
3	Smith BS, Yogaratnam D, Levasseur-Franklin KE, et al.Introduction to drug pharmacokinetics in the critically ill patient [J].Chest, 2012,141(5): 1327-1336.
4	Williams P, Cotta MO, Roberts JA.Pharmacokinetics/pharmacodynamics of β-lactams and therapeutic drug monitoring:from theory to practical issues in the intensive care unit [J].Semin Respir Crit Care Med, 2019, 40(4): 476-487.
5	Sumi CD, Roberts JA, Sime FB.Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Klebsiella pneumoniae-authors’ response [J].J Antimicrob Chemother, 2023,78(3): 854-857.
6	McKinnon PS, Paladino JA, Schentag JJ.Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T＞MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections [J].Int J Antimicrob Agents,2008, 31(4): 345-351.
7	Yadav R, Bergen PJ, Rogers KE, et al.Meropenem-tobramycin combination regimens combat carbapenem-resistant Pseudomonas aeruginosa in the hollow-fiber infection model simulating augmented renal clearance in critically ill patients [J].Antimicrob Agents Chemother, 2019, 64(1): e01679-01619.
8	Jeremy Howick, Iain Chalmers, Paul Glasziou, et al.Explanation of the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM)Levels of Evidence (Background Document) [EB/OL].Oxford Centre for Evidence-Based Medicine.https: //www.cebm.ox.ac.uk/resources/levels-of-evidence/explanation-of-the-2011-ocebm-levelsof-evidence/.
9	中华医学会消化病学分会炎症性肠病学组, 中国炎症性肠病诊疗质量控制评估中心.中国克罗恩病诊治指南(2023 年·广州) [J].中华消化杂志, 2024, 44(2): 100-132.
10	Udy AA, Roberts JA, Lipman J.Implications of augmented renal clearance in critically ill patients [J].Nat Rev Nephrol, 2011, 7(9):539-543.
11	Veiga RP, Paiva JA.Pharmacokinetics-pharmacodynamics issues relevant for the clinical use of beta-lactam antibiotics in critically ill patients [J].Crit Care, 2018, 22(1): 233.
12	Luo Y, Wang Y, Ma Y, et al.Augmented renal clearance: what have we known and what will we do? [J].Front Pharmacol, 2021, 12: 723731.
13	Carrié C, Petit L, d’Houdain N, et al.Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of β-lactams administered by continuous infusion: a prospective observational study [J].Int J Antimicrob Agents, 2018, 51(3): 443-449.
14	Schleibinger M, Steinbach CL, Töpper C, et al.Protein binding characteristics and pharmacokinetics of ceftriaxone in intensive care unit patients [J].Br J Clin Pharmacol, 2015, 80(3): 525-533.
15	Pea F, Viale P, Furlanut M.Antimicrobial therapy in critically ill patients: a review of pathophysiological conditions responsible for altered disposition and pharmacokinetic variability [J].Clin Pharmacokinet, 2005, 44(10): 1009-1034.
16	Jang SM, Gharibian KN, Lewis SJ, et al.A Monte Carlo simulation approach for beta-lactam dosing in critically ill patients receiving prolonged intermittent renal replacement therapy [J].J Clin Pharmacol,2018, 58(10): 1254-1265.
17	Dzierba AL, Abrams D, Brodie D.Medicating patients during extracorporeal membrane oxygenation: the evidence is building [J].Crit Care, 2017, 21(1): 66.
18	Winstead EM, Ratliff PD, Hickson RP, et al.Evaluation of an alternative extended-infusion piperacillin-tazobactam dosing strategy for the treatment of gram-negative infections [J].Int J Clin Pharm,2016, 38(5): 1087-1093.
19	Ollivier J, Carrié C, d’Houdain N, et al.Are standard dosing regimens of Ceftriaxone adapted for critically ill patients with augmented creatinine clearance? [J].Antimicrob Agents Chemother, 2019, 63(3):e02134-02118.
20	Rhodes NJ, Kuti JL, Nicolau DP, et al.Defining clinical exposures of Cefepime for gram-negative bloodstream infections that are associated with improved survival [J].Antimicrob Agents Chemother, 2015,60(3): 1401-1410.
21	Beumier M, Casu GS, Hites M, et al.Elevated β-lactam concentrations associated with neurological deterioration in ICU septic patients [J].Minerva Anestesiol, 2015, 81(5): 497-506.
22	Chytra I, Stepan M, Benes J, et al.Clinical and microbiological efficacy of continuous versus intermittent application of meropenem in critically ill patients: a randomized open-label controlled trial [J].Crit Care, 2012, 16(3): R113.
23	Fan SY, Shum HP, Cheng WY, et al.Clinical outcomes of extended versus intermittent infusion of Piperacillin/Tazobactam in critically ill patients: a prospective clinical trial [J].Pharmacotherapy, 2017, 37(1):109-119.
24	Yang H, Zhang C, Zhou Q, et al.Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic review and meta-analysis [J].PLoS One, 2015, 10(1): e0116769.
25	Nast CC.Medication-induced interstitial nephritis in the 21st century[J].Adv Chronic Kidney Dis, 2017, 24(2): 72-79.
26	Maguigan KL, Al-Shaer MH, Peloquin CA.Beta-lactams dosing in critically ill patients with gram-negative bacterial infections: a PK/PD approach [J].Antibiotics (Basel), 2021, 10(10): 1154.
27	Kondo Y, Ota K, Imura H, et al.Prolonged versus intermittent β-lactam antibiotics intravenous infusion strategy in sepsis or septic shock patients: a systematic review with meta-analysis and trial sequential analysis of randomized trials [J].J Intensive Care, 2020, 8: 77.
28	Bouhanick B, Barbosa SS.Rapaglinide: Novonorm, an alternative in type 2 diabetes [J].Presse Med, 2000, 29(19): 1059-1061.
29	Zhao Y, Zang B, Wang Q.Prolonged versus intermittent β-lactam infusion in sepsis: a systematic review and meta-analysis of randomized controlled trials [J].Ann Intensive Care, 2024, 14(1): 30.
30	Dulhunty JM, Brett SJ, De Waele JJ, et al.Continuous vs Intermittent β-lactam antibiotic infusions in critically ill patients with sepsis: the BLING III randomized clinical trial [J].JAMA, 2024, 332(8): 629-637.
31	叶龙强, 石林惠, 董绉绉.延长头孢哌酮/舒巴坦输注时间治疗重症监护病房鲍曼不动杆菌肺炎的临床研究 [J].中华临床感染病杂志, 2015, 8(2): 164-166.
32	Monti G, Bradic N, Marzaroli M, et al.Continuous vs intermittent Meropenem administration in critically ill patients with sepsis: the MERCY randomized clinical trial [J].JAMA, 2023, 330(2): 141-151.
33	Goncette V, Layios N, Descy J, et al.Continuous infusion, therapeutic drug monitoring and outpatient parenteral antimicrobial therapy with ceftazidime/avibactam: a retrospective cohort study [J].J Glob Antimicrob Resist, 2021, 26: 15-19.
34	Cojutti PG, Lazzarotto D, Candoni A, et al.Real-time TDM-based optimization of continuous-infusion meropenem for improving treatment outcome of febrile neutropenia in oncohaematological patients: results from a prospective, monocentric, interventional study[J].J Antimicrob Chemother, 2020, 75(10): 3029-3037.
35	Fawaz S, Barton S, Nabhani-Gebara S.Comparing clinical outcomes of piperacillin-tazobactam administration and dosage strategies in critically ill adult patients: a systematic review and meta-analysis [J].BMC Infect Dis, 2020, 20(1): 430.
36	Sinnollareddy MG, Roberts MS, Lipman J, et al.β-lactam pharmacokinetics and pharmacodynamics in critically ill patients and strategies for dose optimization: a structured review [J].Clin Exp Pharmacol Physiol, 2012, 39(6): 489-496.
37	Jaruratanasirikul S, Boonpeng A, Nawakitrangsan M, et al.NONMEM population pharmacokinetics and Monte Carlo dosing simulations of imipenem in critically ill patients with life-threatening severe infections during support with or without extracorporeal membrane oxygenation in an intensive care unit [J].Pharmacotherapy, 2021,41(7): 572-597.
38	Garot D, Respaud R, Lanotte P, et al.Population pharmacokinetics of ceftriaxone in critically ill septic patients: a reappraisal [J].Br J Clin Pharmacol, 2011, 72(5): 758-767.
39	Hayashi Y, Lipman J, Udy AA, et al.β-lactam therapeutic drug monitoring in the critically ill: optimising drug exposure in patients with fluctuating renal function and hypoalbuminaemia [J].Int J Antimicrob Agents, 2013, 41(2): 162-166.
40	Casu GS, Hites M, Jacobs F, et al.Can changes in renal function predict variations in β-lactam concentrations in septic patients? [J].Int J Antimicrob Agents, 2013, 42(5): 422-428.
41	Neuner EA, Ahrens CL, Groszek JJ, et al.Use of therapeutic drug monitoring to treat Elizabethkingia meningoseptica meningitis and bacteraemia in an adult [J].J Antimicrob Chemother, 2012, 67(6):1558-1560.
42	Sime FB, Roberts MS, Tiong IS, et al.Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial [J].J Antimicrob Chemother, 2015, 70(8): 2369-2375.
43	De Waele JJ, Carrette S, Carlier M, et al.Therapeutic drug monitoringbased dose optimisation of piperacillin and meropenem: a randomised controlled trial [J].Intensive Care Med, 2014, 40(3): 380-387.
44	Richter DC, Frey O, Röhr A, et al.Therapeutic drug monitoringguided continuous infusion of piperacillin/tazobactam significantly improves pharmacokinetic target attainment in critically ill patients: a retrospective analysis of four years of clinical experience [J].Infection,2019, 47(6): 1001-1011.
45	Dräger S, von Rotz M, Labhardt ND, et al.Early target attainment with continuous infusion Meropenem and Piperacillin/Tazobactam and utilization of therapeutic drug monitoring in critically ill patients: a retrospective cohort study from 2017 to 2020 [J].Open Forum Infect Dis, 2023, 10(4): ofad143.
46	Loeuille G, D’Huart E, Vigneron J, et al.Stability studies of 16 antibiotics for continuous infusion in intensive care units and for performing outpatient parenteral antimicrobial therapy [J].Antibiotics(Basel), 2022, 11(4): 458.
47	Xia M, Hang TJ, Zhang F, et al.The stability of Biapenem and structural identification of impurities in aqueous solution [J].J Pharm Biomed Anal, 2009, 49(4): 937-944.
48	Kuti JL, Nicolau DP.Stability of Ertapenem 100 mg/ml at room temperature [J].Can J Hosp Pharm, 2016, 69(3): 256-259.
49	McQuade MS, Van Nostrand V, Schariter J, et al.Stability and compatibility of reconstituted Ertapenem with commonly used i.v.infusion and coinfusion solutions [J].Am J Health Syst Pharm, 2004,61(1): 38-45.
50	Yu Z, Pang X, Wu X, et al.Clinical outcomes of prolonged infusion(extended infusion or continuous infusion) versus intermittent bolus of meropenem in severe infection: a meta-analysis [J].PLoS One, 2018,13(7): e0201667.
51	Jamal JA, Roberts DM, Udy AA, et al.Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration [J].Int J Antimicrob Agents,2015, 46(1): 39-44.
52	Boselli E, Breilh D, Rimmelé T, et al.Alveolar concentrations of piperacillin/tazobactam administered in continuous infusion to patients with ventilator-associated pneumonia [J].Crit Care Med, 2008, 36(5):1500-1506.
53	Al-Shaer MH, Philpott CD, Droege CA, et al.Cefepime population pharmacokinetics and target attainment in critically ill patients on continuous renal replacement therapy [J].Antimicrob Agents Chemother, 2021, 65(6): e00144-00121.
54	Ahmed N, Jen SP, Altshuler D, et al.Evaluation of Meropenem extended versus intermittent infusion dosing protocol in critically ill patients [J].J Intensive Care Med, 2020, 35(8): 763-771.
55	Fehér C, Rovira M, Soriano A, et al.Effect of Meropenem administration in extended infusion on the clinical outcome of febrile neutropenia: a retrospective observational study [J].J Antimicrob Chemother, 2014,69(9): 2556-2562.
56	侯钦云, 赵京春, 姜红.注射用头孢哌酮钠/舒巴坦钠的稳定性研究 [J].医药导报, 2009, 28(7): 946-948.
57	Dong J, Xiong W, Chen Y, et al.Optimal dosing regimen of Biapenem in Chinese patients with lower respiratory tract infections based on population pharmacokinetic/pharmacodynamic modelling and Monte Carlo simulation [J].Int J Antimicrob Agents, 2016, 47(3): 202-209.
58	司马燕.泵注比阿培南延长给药时间治疗ICU 重症肺炎的效果及安全性观察 [J].中外医学研究, 2018, 16(30): 25-27.
59	徐继来.泵注比阿培南延长给药时间治疗ICU 重症感染临床分析[J].中国实用医药, 2018, 13(35): 119-120.
60	孙章萍, 程志华, 闫福栋, 等.比阿培南延长输注治疗重症肺炎患者的疗效及药物经济学评价 [J].中国药物经济学, 2020, 15(12):39-41, 50.
61	Boselli E, Breilh D, Rimmelé T, et al.Plasma and lung concentrations of ceftazidime administered in continuous infusion to critically ill patients with severe nosocomial pneumonia [J].Intensive Care Med,2004, 30(5): 989-991.
62	栗兰, 李明艳, 赖军华.延长输注比阿培南治疗重症肺炎的疗效与药物经济学分析 [J].中国药物警戒, 2016, 13(1): 50-51, 56.
63	Sumi CD, Heffernan AJ, Lipman J, et al.What antibiotic exposures are required to suppress the emergence of resistance for Gram-Negative Bacteria? A systematic review [J].Clin Pharmacokinet, 2019, 58(11):1407-1443.
64	Jacobs DM, DiTursi S, Ruh C, et al.Combination treatment with extended-infusion ceftazidime/avibactam for a KPC-3-producing Klebsiella pneumoniae bacteraemia in a kidney and pancreas transplant patient [J].Int J Antimicrob Agents, 2016, 48(2): 225-227.
65	van Duin D, Bonomo RA.Ceftazidime/Avibactam and Ceftolozane/Tazobactam: second-generation β-lactam/β-lactamase inhibitor combinations [J].Clin Infect Dis, 2016, 63(2): 234-241.
66	Falcone M, Menichetti F, Cattaneo D, et al.Pragmatic options for dose optimization of ceftazidime/avibactam with aztreonam in complex patients [J].J Antimicrob Chemother, 2021, 76(4): 1025-1031.
67	Leegwater E, Kraaijenbrink B, Moes D, et al.Population pharmacokinetics of ceftriaxone administered as continuous or intermittent infusion in critically ill patients [J].J Antimicrob Chemother, 2020, 75(6): 1554-1558.
68	Aubert G, Carricajo A, Coudrot M, et al.Prospective determination of serum ceftazidime concentrations in intensive care units [J].Ther Drug Monit, 2010, 32(4): 517-519.
69	Buijk SL, Gyssens IC, Mouton JW, et al.Pharmacokinetics of ceftazidime in serum and peritoneal exudate during continuous versus intermittent administration to patients with severe intra-abdominal infections [J].J Antimicrob Chemother, 2002, 49(1): 121-128.
70	Cousson J, Floch T, Guillard T, et al.Lung concentrations of ceftazidime administered by continuous versus intermittent infusion in patients with ventilator-associated pneumonia [J].Antimicrob Agents Chemother, 2015, 59(4): 1905-1909.
71	Nicolau DP, McNabb J, Lacy MK, et al.Continuous versus intermittent administration of ceftazidime in intensive care unit patients with nosocomial pneumonia [J].Int J Antimicrob Agents, 2001, 17(6): 497-504.
72	Jacobs A, Taccone FS, Roberts JA, et al.β-lactam dosage regimens in septic patients with augmented renal clearance [J].Antimicrob Agents Chemother, 2018, 62(9): e02534-02517.
73	Liu J, Neely M, Lipman J, et al.Development of population and Bayesian models for applied use in patients receiving Cefepime [J].Clin Pharmacokinet, 2020, 59(8): 1027-1036.
74	Burgess DS, Hastings RW, Hardin TC.Pharmacokinetics and pharmacodynamics of cefepime administered by intermittent and continuous infusion [J].Clin Ther, 2000, 22(1): 66-75.
75	Nicasio AM, Ariano RE, Zelenitsky SA, et al.Population pharmacokinetics of high-dose, prolonged-infusion cefepime in adult critically ill patients with ventilator-associated pneumonia [J].Antimicrob Agents Chemother, 2009, 53(4): 1476-1481.
76	Bauer KA, West JE, O'Brien JM, et al.Extended-infusion cefepime reduces mortality in patients with Pseudomonas aeruginosa infections[J].Antimicrob Agents Chemother, 2013, 57(7): 2907-2912.
77	Georges B, Conil JM, Cougot P, et al.Cefepime in critically ill patients: continuous infusion vs.an intermittent dosing regimen [J].Int J Clin Pharmacol Ther, 2005, 43(8): 360-369.
78	Turner RB, Slain D, Petros K, et al.Clinical outcomes following hospital-wide implementation of prolonged-infusion cefepime and ceftazidime [J].Int J Antimicrob Agents, 2015, 46(1): 129-130.
79	Vourli S, Tsala M, Kotsakis S, et al.Comparison of short versus prolonged infusion of standard dose of Meropenem against Carbapenemase-producing Klebsiella pneumoniae isolates in different patient groups: a pharmacokinetic-pharmacodynamic approach [J].J Pharm Sci, 2016, 105(4): 1513-1518.
80	王振红, 单悌超, 刘宇, 等.美罗培南3 h 和30 min 输注给药治疗重症监护病房患者医院获得性肺炎的随机对照临床研究 [J].中华危重病急救医学, 2014, 26(9): 644-649.
81	Lokhandwala A, Patel P, Isaak AK, et al.Comparison of the effectiveness of prolonged infusion and intermittent infusion of Meropenem in patients with sepsis: a meta-analysis [J].Cureus, 2023,15(10): e46990.
82	Abdul-Aziz MH, Hammond NE, Brett SJ, et al.Prolonged vs intermittent infusions of β-lactam antibiotics in adults with sepsis or septic shock: a systematic review and meta-analysis [J].JAMA, 2024,332(8): 638-648.
83	Liebchen U, Kratzer A, Wicha SG, et al.Unbound fraction of Ertapenem in intensive care unit patients [J].J Antimicrob Chemother,2014, 69(11): 3108-3111.
84	Boselli E, Breilh D, Saux MC, et al.Pharmacokinetics and lung concentrations of Ertapenem in patients with ventilator-associated pneumonia [J].Intensive Care Med, 2006, 32(12): 2059-2062.
85	Burkhardt O, Kumar V, Katterwe D, et al.Ertapenem in critically ill patients with early-onset ventilator-associated pneumonia:pharmacokinetics with special consideration of free-drug concentration[J].J Antimicrob Chemother, 2007, 59(2): 277-284.
86	Hang Y, Chen Y, Xue L, et al.Evaluating Biapenem dosage regimens in intensive care unit patients with Pseudomonas aeruginosa infections:a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation [J].Int J Antimicrob Agents, 2018, 51(3): 484-487.
87	Abdul-Aziz MH, Lipman J, Akova M, et al.Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort [J].J Antimicrob Chemother, 2016, 71(1): 196-207.
88	Bao H, Lv Y, Wang D, et al.Clinical outcomes of extended versus intermittent administration of piperacillin/tazobactam for the treatment of hospital-acquired pneumonia: a randomized controlled trial [J].Eur J Clin Microbiol Infect Dis, 2017, 36(3): 459-466.
89	Carlier M, Carrette S, Roberts JA, et al.Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used? [J].Crit Care, 2013, 17(3): R84.
90	Roberts JA, Kirkpatrick CM, Roberts MS, et al.First-dose and steady-state population pharmacokinetics and pharmacodynamics of piperacillin by continuous or intermittent dosing in critically ill patients with sepsis [J].Int J Antimicrob Agents, 2010, 35(2): 156-163.
91	叶龙强, 石林惠, 董绉绉.延长头孢哌酮/舒巴坦输注时间治疗重症监护病房鲍曼不动杆菌肺炎的临床研究 [J].中华临床感染病杂志, 2015, 8(2): 164-166.
92	李小玲, 董利民, 廖洁, 等.头孢哌酮舒巴坦 (舒普深) 延长及持续输注在绿脓杆菌肺炎中的疗效对比研究 [J].赣南医学院学报,2020, 40(4): 396-399.
93	Roger C, Louart B.Beta-lactams toxicity in the intensive care unit: an underestimated collateral damage? [J].Microorganisms, 2021, 9(7):1505.
94	Veillette JJ, Truong J, Forland SC.Pharmacokinetics of Ceftazidime-Avibactam in two patients with KPC-producing Klebsiella pneumoniae bacteremia and renal impairment [J].Pharmacotherapy, 2016, 36(11):e172-e177.
95	Gatti M, Pea F.Continuous versus intermittent infusion of antibiotics in Gram-negative multidrug-resistant infections [J].Curr Opin Infect Dis, 2021, 34(6): 737-747.
96	Tumbarello M, Raffaelli F, Giannella M, et al.Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase-producing K.pneumoniae infections: a retrospective observational multicenter study[J].Clin Infect Dis, 2021, 73(9): 1664-1676.
97	Cowart MC, Ferguson CL.Optimization of Aztreonam in combination with Ceftazidime/Avibactam in a cystic fibrosis patient with chronic Stenotrophomonas maltophilia pneumonia using therapeutic drug monitoring: a case study [J].Ther Drug Monit, 2021, 43(2): 146-149.
98	Tamma PD, Fan Y, Bergman Y, et al.Successful treatment of persistent Burkholderia cepacia complex bacteremia with Ceftazidime-Avibactam [J].Antimicrob Agents Chemother, 2018, 62(4): e02213-02217.
99	Suchánková H, Lipš M, Urbánek K, et al.Is continuous infusion of imipenem always the best choice? [J].Int J Antimicrob Agents, 2017,49(3): 348-354.
100	Huang Y, Xu K, Zhan Y, et al.Comparable effect of two-step versus extended infusions on the pharmacokinetics of imipenem in patients with sepsis and septic shock [J].Adv Ther, 2020, 37(5): 2246-2255.
101	Ibrahim MM, Tammam TF, Ebaed M, et al.Extended infusion versus intermittent infusion of imipenem in the treatment of ventilatorassociated pneumonia [J].Drug Des Devel Ther, 2017, 11:2677-2682.
102	郭新成, 孟浩, 苗云凤.亚胺培南西司他丁0.5g/2h 输注对重症肺炎患者的治疗效果 [J].临床医学研究与实践, 2020, 5(25): 62-64.
103	王晓雯, 刘澄英.亚胺培南西司他丁在不同输注持续时间下对重症肺炎的临床疗效比较 [J].北方药学, 2016, 13(11): 91.
104	叶少波, 黄跃清, 冯宝华.亚胺培南西司他丁不同输注持续时间治疗重症肺炎的疗效研究 [J].北方药学, 2016, 13(4): 94, 下转93.
105	Viaene E, Chanteux H, Servais H, et al.Comparative stability studies of antipseudomonal beta-lactams for potential administration through portable elastomeric pumps (home therapy for cystic fibrosis patients)and motor-operated syringes (intensive care units) [J].Antimicrob Agents Chemother, 2002, 46(8): 2327-2332.
106	Marshall S, Hujer AM, Rojas LJ, et al.Can Ceftazidime-Avibactam and Aztreonam overcome β-lactam resistance conferred by Metallo-βlactamases in Enterobacteriaceae? [J].Antimicrob Agents Chemother,2017, 61(4): e02243-02216.
107	Gross AE, Xu H, Zhou D, et al.Simplified Aztreonam dosing in patients with end-stage renal disease: results of a Monte Carlo simulation [J].Antimicrob Agents Chemother, 2018, 62(11): e01066-01018.
108	Cornwell EE 3rd, Belzberg H, Berne TV, et al.Pharmacokinetics of aztreonam in critically ill surgical patients [J].Am J Health Syst Pharm, 1997, 54(5): 537-540.
109	Burgess DS, Summers KK, Hardin TC.Pharmacokinetics and pharmacodynamics of aztreonam administered by continuous intravenous infusion [J].Clin Ther, 1999, 21(11): 1882-1889.

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
药品名	说明书用法	临床研究用法举例	说明书稳定性
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）^［58-60］	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

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
药品名	说明书用法	临床研究用法举例	说明书稳定性
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）^［58-60］	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

[1]	Yan Zhuang, Linfeng Dai, Haidong Zhang, Qiuhua Chen, Qingfang Nie. Risk factors of early survival for sepsis patients and construction of a Cox risk prediction model [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2024, 17(05): 372-378.
[2]	Jin Yang, Xueke Liu, Yuanyuan Zhang, Jun Jin, Yao Wei. Protective effect of gut microbiota-derived lithocholic acid on sepsis-associated hepatic injury [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2024, 17(04): 265-274.
[3]	Xia Zhang, Rui Zhang, Zhibo Zheng, Qin Zhang. Shikonin improves prognosis of mice with sepsis-induced cardiomyopathy by modulating lactylation and mitochondrial function [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2024, 17(04): 275-284.
[4]	Jingqi Zhang, Yang Jiang, Jialu Sun, Xingzhe Tang, Yufei Zhao, Ying Cui, Xinxiang Li, Jingyue Dai, lin Fu, Xingui Peng. Early identification of sepsis with acute kidney injury by perirenal CT features combined with serum creatinine [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2024, 17(04): 285-292.
[5]	Zhenhe Li, Changqing Wei, Guodong Zhen, Zhenfu Li. Changes of serum S1P and Wnt5a in patients with sepsis complicating acute respiratory distress syndrome and their clinical significance [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2024, 17(04): 293-300.
[6]	Heng Fan, Min Sun, Jianhua Zhu. Protective effect of salidroside on septic acute kidney injury in rats by inhibiting phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin signal pathway [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2024, 17(03): 188-195.
[7]	Yajuan Jia, Yuming Meng, Zhiwei Gao, Sumin Gao, Jinsong Zhang, Hong Sun. Predictive value of combined detection of platelet to lymphocyte ratio, procalcitonin and interleukin-6 in prognosis of patients with sepsis [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2024, 17(02): 118-123.
[8]	Boxing Su, Bo Xiao, Jianxing Li. Hot research and interpretation of surgical therapy for stone disease in the annual meeting of American Urology Association in 2024 [J]. Chinese Journal of Endourology(Electronic Edition), 2024, 18(04): 303-308.
[9]	Xi Chen, Zongsheng Wu, Mingzhu Zheng, Haibo Qiu. Research progress in sepsis immune disorder: thymic atrophy [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(04): 379-383.
[10]	Xiang Yang, Lanqi Guo, Jianfeng Xie, Haibo Qiu. Advances in transcriptomics in diagnosis and management of sepsis [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(04): 384-388.
[11]	Zihan Hu, Fei Peng, Qin Sun, Yi Yang. Research progress of extracellular vesicles in vascular endothelial dysfunction in sepsis [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(03): 265-270.
[12]	Juanli Liu, Siqing Ma, Wurentana. Research progress of myeloid derived suppressor cells in sepsis [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(03): 271-278.
[13]	Shenglin Su, Jinlan Ma, Hongming Yu, Xiaojun Yang. Application of single cell sequencing technology in the study of sepsis immunity [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(03): 279-286.
[14]	Huiying Chen, Minshan Qiu, Hanquan Shao. Construction and application effect of risk factor model for intestinal mucosal barrier function damage induced by sepsis [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2024, 14(05): 448-452.
[15]	Jingni Xi, Na Li, Qi Zhang. Predictive value of neutrophil-to-lymphocyte ratio for progression of severe community-acquired pneumonia to sepsis in elderly patients [J]. Chinese Journal of Geriatrics Research(Electronic Edition), 2024, 11(03): 28-31.

Please choose a citation manager

Content to export