2015年3月進(jìn)修視頻2課件clnical implications for antimicrobial therapy

1、藥代動(dòng)力學(xué)與重癥感染的抗生素治療北京協(xié)和醫(yī)院杜斌利益沖突美國(guó)禮來(lái)公司全身性感染：中國(guó)與歐洲PortugalUK + IrelandEastern EuropeItalyNetherlandsSpainAustriaFranceGreeceScandinaviaGermanySwitzerlandBelgiumChinaVincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 2006; 34: 344-353Du

2、B, An Y, Kang Y, et al. Characteristics of critically ill patients in intensive care units in mainland China. Crit Care Med 2012 (in press)全身性感染：中國(guó)與歐洲Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 2006; 34: 344-353Du B, An Y, K

3、ang Y, et al. Characteristics of critically ill patients in intensive care units in mainland China. Crit Care Med 2012 (in press)CCCCTG(n = 484)歐洲(n = 1177)PICU住院日8 (4 16)6.9 (3.1 15.0)總住院日19 (10 43)17.8 (8.0 38.2)ICU病死率139 (29%)313 (27%)0.410住院病死率162 (34%)413 (36%)0.567感染性休克的早期經(jīng)驗(yàn)性抗生素治療Kumar A, Robe

4、rts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34: 1589-1596合并感染性休克的侵襲性念珠菌?。涸缙诔浞值慕?jīng)驗(yàn)性抗真菌治療Kollef M, Micek S, Hampton N, et al. Septic shock attributed to Candida inf

5、ection: importance of empiric therapy and source control. Clin Infect Dis 2012; 54: 1739-1746Surviving Sepsis Campaign Guideline 2012D. 抗生素治療我們推薦初始的抗生素治療應(yīng)當(dāng)包括對(duì)所有可能致病微生物（細(xì)菌和或真菌或病毒）有效的一種或多種藥物(Grade 1B)Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for manage

6、ment of severe sepsis and septic shock: 2012. Crit Care Med 2012 (in press)萬(wàn)古霉素與-內(nèi)酰胺治療MSSA菌血癥Chang FY, Peacock JE Jr, Musher DM, et al. Staphylococcus aureus bacteremia: recurrence and the imapct of antibiotic treatment in a prospective multicenter study. Medicine (Baltimore) 2003; 82: 333-339萬(wàn)古霉素與利

7、奈唑胺治療MRSA醫(yī)院獲得性肺炎：ZEPHyRWunderink RG, Niederman MS, Kollef MH, et al. Linezolid in methicillin-resistant Staphylococcus aureus ial pneumonia: a randomized, controlled study. Clin Infect Dis 2012; 54: 621-62995/16581/174P = 0.04295%CI: 0.5 to 21.6利奈唑胺臨床治愈率顯著高于萬(wàn)古霉素如何改進(jìn)臨床療效抗生素分類(lèi)：時(shí)間依賴(lài)性與濃度依賴(lài)性del Castillo

8、JRE, Elsener J, Martineau GP. Pharmacokinetic modeling of in-feed tetracyclines in pigs using a meta-analytic compartmental approach. Swine Health and Production 1998; 6: 189-202抗生素分類(lèi)：時(shí)間依賴(lài)性與濃度依賴(lài)性Adapted from: Southwick F (2008): Anti-Infective Therapy (Chapter 1). In: Infectious Diseases. A Clinical

9、 Short Course. McGraw Hill. Pg 5.(ISBN: 978-0-07-1477222)抗生素分類(lèi)：時(shí)間依賴(lài)性與濃度依賴(lài)性病例男性，20歲，病歷號(hào)17338926月25日刀刺傷，心肺復(fù)蘇術(shù)后，右心室破裂修補(bǔ)，右肺下葉修補(bǔ)，膈肌修補(bǔ)術(shù)后，雙側(cè)去骨瓣減壓術(shù)后7月17日入院當(dāng)日外周血培養(yǎng)MRSA7月19日應(yīng)用萬(wàn)古霉素1.0 g q12h1.0 q12h7/192.92 mg/L7/232.0 q12h7/235.61 mg/L7/246.18 mg/L7/272.0 q8h7/2737.02 mg/L7/302.0 q12h7/3015.76 mg/L7/3113.31 m

10、g/L8/19.93 mg/L8/22.5 g q12h8/217.52 mg/L8/6藥代動(dòng)力學(xué)基本原理吸收(absorption)分布(distribution)代謝(metabolism)排泄(excretion)藥代動(dòng)力學(xué)：一室模型single componentkkaKa = 吸收速率常數(shù)k = 清除速率常數(shù)藥代動(dòng)力學(xué)：一室模型表觀(guān)分布容積Vd = D/Cp半衰期t1/2 = 0.693/k清除率CLtotal = CLrenal + CLnonrenalt1/2 = 0.693 x Vd/CLtotal藥代動(dòng)力學(xué)：重要參數(shù)表觀(guān)分布容積Vd = D / Cp半衰期t1/2 = 0.6

11、93 / k清除率CLtotal = CLrenal + CLnonrenalt1/2 = 0.693 x Vd / CLtotalCp: 血藥濃度；D: 藥物劑量；Vd: 分布容積t1/2: 半衰期；k: 清除速率常數(shù)CLtotal: 藥物清除率；CLrenal: 藥物經(jīng)腎臟清除率；CLnonrenal: 藥物經(jīng)非腎臟途徑清除率藥代動(dòng)力學(xué)：二室模型peripheralcentralk12k21kDrug ink12 = 中央室向外周室轉(zhuǎn)運(yùn)速率常數(shù)k21 = 外周室向中央室轉(zhuǎn)運(yùn)速率常數(shù)k = 中央室清除率藥代動(dòng)力學(xué)：二室模型CplogCpTimeTime藥代動(dòng)力學(xué)：多次用藥根據(jù)規(guī)律時(shí)間間隔用藥

12、時(shí)，血藥濃度逐漸升高直至達(dá)到穩(wěn)態(tài)，即一定時(shí)間內(nèi)用藥量與清除藥物量相等藥代動(dòng)力學(xué)：多次用藥時(shí)藥物劑量的影響藥物劑量*越大，穩(wěn)態(tài)藥物濃度越高藥物劑量*越大，Cp max與Cp min差異越大達(dá)到穩(wěn)態(tài)藥物濃度的時(shí)間與劑量無(wú)關(guān)*維持劑量藥代動(dòng)力學(xué)：多次用藥時(shí)給藥間隔的影響給藥間隔短于半衰期，導(dǎo)致藥物蓄積，Cp max與Cp min差異減小給藥間隔超過(guò)半衰期，藥物蓄積較少，Cp max與Cp min差異增加藥代動(dòng)力學(xué)：穩(wěn)態(tài)濃度前藥代動(dòng)力學(xué)：穩(wěn)態(tài)濃度D:維持劑量CL:藥物清除率:給藥間隔藥代動(dòng)力學(xué)：穩(wěn)態(tài)濃度D:維持劑量t1/2:半 衰 期Vd:分布容積:給藥間隔藥代動(dòng)力學(xué)：維持劑量維持劑量Cssp: 穩(wěn)態(tài)

13、血藥濃度CL (L/h): 藥物清除率，指單位時(shí)間內(nèi)多少容積血漿內(nèi)總的藥物經(jīng)代謝和（或）分泌途徑清除干凈: 給藥時(shí)間間隔當(dāng)給藥時(shí)間間隔及血藥濃度目標(biāo)確定時(shí)，維持劑量(D)僅與藥物清除率(CL)相關(guān)藥代動(dòng)力學(xué)：藥物清除率CLtotal = CLrenal + CLnonrenal = k x Vdt1/2 = 0.693 x Vd / CL藥物清除率與肌酐清除率Matzke GR, McGory RW, Halstenson CE, et al. Pharmacokinetics of ycin in patients with various degrees of renal function

14、. Antimicrob Agents Chemother 1984; 25: 433-437肌酐清除率對(duì)穩(wěn)態(tài)濃度的影響Roberts JA, Taccone FS, Udy AA, et al. ycin dosing in critically ill patients: robust methods for improved continuous-infusion regimens. Antimicrob Agents Chemother 2011; 55: 2704-2709Loading35 mg/kgMaintenance35 mg/kg/d維持劑量對(duì)穩(wěn)態(tài)濃度的影響Roberts

15、JA, Taccone FS, Udy AA, et al. ycin dosing in critically ill patients: robust methods for improved continuous-infusion regimens. Antimicrob Agents Chemother 2011; 55: 2704-2709CrCl100 ml/min/1.73 m2Loading 35 mg/kg/dPCI術(shù)后維持劑量氯吡格雷Patti G, Grieco D, Dicuonzo G, et al. High versus standard clopidogrel

16、maintenance dose after percutaneous coronary intervention and effects on platelet inhibition, endothelial function, and inflammation. Results of the ARMYDA-150 mg (antiplatelet therapy for reduction of myocardial damage during angioplasty) randomized study. J Am Coll Cardiol 2011; 57: 771-778PCI術(shù)后維持

17、劑量氯吡格雷Patti G, Grieco D, Dicuonzo G, et al. High versus standard clopidogrel maintenance dose after percutaneous coronary intervention and effects on platelet inhibition, endothelial function, and inflammation. Results of the ARMYDA-150 mg (antiplatelet therapy for reduction of myocardial damage dur

18、ing angioplasty) randomized study. J Am Coll Cardiol 2011; 57: 771-778藥代動(dòng)力學(xué)：達(dá)到穩(wěn)態(tài)所需時(shí)間影響因素劑量給藥次數(shù)給藥間隔半衰期：約需4 5個(gè)半衰期達(dá)到穩(wěn)態(tài)血藥濃度腎臟功能不全時(shí)萬(wàn)古霉素的藥代動(dòng)力學(xué)Group 1(n = 10)Group 2(n = 14)Group 3(n = 13)SCr (mg/dl)1.1 0.51.4 0.62.1 1.0CrCl (ml/min/1.73 m2)93.4 28.351.0 8.323.9 8.2Albumin (g/dl)2.6 0.52.6 0.72.4 0.6AUC0-

19、(mg.h/L)135 53264 89451 214t1/2 (h)0.40 0.200.49 0.320.51 0.21t1/2 (h)5.2 2.610.5 3.619.9 10.2Vl (L/kg)0.21 0.110.21 0.140.24 0.12Vss (L/kg)0.50 0.200.59 0.270.64 0.18CL (ml/min/1.73 m2)98.4 24.352.6 17.731.3 14.9CLR (ml/min/1.73 m2) 88.0 33.648.2 10.819.8 7.9Protein binding (%)30.2 9.829.8 6.530.9

20、6.8Rodvold KA, Blum RA, Fischer JH, et al. ycin pharmacokinetics in patients with various degrees of renal function. Antimicrob Agents Chemother 1988; 32: 848-852腎臟功能不全時(shí)萬(wàn)古霉素的半衰期Matzke GR, McGory RW, Halstenson CE, et al. Pharmacokinetics of ycin in patients with various degrees of renal function. An

21、timicrob Agents Chemother 1984; 25: 433-437藥代動(dòng)力學(xué)：靜脈輸注Cssp: 穩(wěn)態(tài)濃度D: 用藥劑量: 半衰期CL: 藥物清除率up to 100750 hrs藥代動(dòng)力學(xué)：停止靜脈輸注藥代動(dòng)力學(xué)：負(fù)荷劑量負(fù)荷劑量的重要性Roberts JA, Taccone FS, Udy AA, et al. ycin dosing in critically ill patients: robust methods for improved continuous-infusion regimens. Antimicrob Agents Chemother 2011;

22、 55: 2704-2709CrCl100 ml/min/1.73 m2Maintenance 35 mg/kg/d負(fù)荷劑量與分布容積藥物X血藥濃度目標(biāo)30 mg/L分布容積20 L半衰期4 h計(jì)算負(fù)荷劑量D = Vd x Cp = 20 L x 30 mg/L = 600 mg氯吡格雷負(fù)荷劑量與血小板抑制LAllier PL, Ducrocq G, Pranno N, et al. Clopidogrel 600-mg double loading dose achieves stronger platelet inhibition than conventional regimens. J

23、 Am Coll Cardiol 2008; 51: 1066-1072生產(chǎn)時(shí)的硬膜外鎮(zhèn)痛Scrutton MJL, Porter JS, OSullivan G. Comparison of three different loading doses to establish epidural analgesia in labour. Int J Obstet Anesth 1998; 7: 165-169Group 1: Bupivacaine9.375 mg (0.0625% 15 ml)05101520Time (minutes)Group 2: Bupivacaine15 mg (0

24、.1% 15 ml)Group 3: Bupivacaine10 mg (0.25% 4 ml)20 mg (0.25% 8 ml)All groups:Bupivacaine 0.0625%10 12 ml/hr生產(chǎn)時(shí)的硬膜外鎮(zhèn)痛Scrutton MJL, Porter JS, OSullivan G. Comparison of three different loading doses to establish epidural analgesia in labour. Int J Obstet Anesth 1998; 7: 165-169負(fù)荷劑量嗎啡用于術(shù)后鎮(zhèn)痛Aubrun F, A

25、mour J, Rosenthal D, et al. Effects of a loading dose of morphine before iv morphine titration for postoperative pain relief: a randomized, double-blind, placebo-control study. Br J Anaesth 2007; 98: 124-130安慰劑組(n = 50)嗎啡組(n = 50)P值負(fù)荷劑量(mg)010.4 (2.0)負(fù)荷劑量(mg/kg)00.15 (0)劑量調(diào)整36 (72%)27 (54%)0.06劑量調(diào)整次

26、數(shù)4 (3 5)1.5 (0 4)0.08滴定劑量(mg)11.4 (9.9)8.3 (10.3)滴定劑量(mg/kg)0.17 (0.15)0.13 (0.15)0.12麻醉后總劑量(mg)11.4 (9.9)18.7 (10.6)麻醉后總劑量(mg/kg)0.17 (0.15)0.28 (0.15)0.00124小時(shí)PCA劑量(mg)23.7 (16.4)21.0 (21.5)24小時(shí)PCA劑量(mg/kg)0.35 (0.26)0.32 (0.35)0.6624小時(shí)總劑量(mg)35.5 (21.0)39.7 (27.5)24小時(shí)總劑量(mg/kg)0.53 (0.34)0.60 (0.

27、43)0.38負(fù)荷劑量嗎啡用于術(shù)后鎮(zhèn)痛Aubrun F, Amour J, Rosenthal D, et al. Effects of a loading dose of morphine before iv morphine titration for postoperative pain relief: a randomized, double-blind, placebo-control study. Br J Anaesth 2007; 98: 124-130替考拉寧的負(fù)荷劑量Wang J, Liao H, Lin FW, et al. Loading dose required t

28、o achieve rapid therapeutic teicoplanin trough plasma concentration in patients with multi-resistant Gram-positive infections. Basic Clin Pharmacol Toxicol 2012; 110: 416-4200 hr12 hr24 hr36 hr48 hrGroup ATeicoplanin 6 mg/kgGroup BTeicoplanin 12 mg/kg6 mg/kg6 mg/kg6 mg/kg6 mg/kg qd12 mg/kg12 mg/kg12

29、 mg/kg6 mg/kg qd負(fù)荷劑量維持劑量替考拉寧的負(fù)荷劑量Wang J, Liao H, Lin FW, et al. Loading dose required to achieve rapid therapeutic teicoplanin trough plasma concentration in patients with multi-resistant Gram-positive infections. Basic Clin Pharmacol Toxicol 2012; 110: 416-420替考拉寧的負(fù)荷劑量結(jié)論盡管由于樣本量較小且患者腎臟功能差異較大，但本研究仍提示

30、負(fù)荷劑量12 mg/kg替考拉寧能夠安全迅速達(dá)到治療谷濃度，并提高療效Wang J, Liao H, Lin FW, et al. Loading dose required to achieve rapid therapeutic teicoplanin trough plasma concentration in patients with multi-resistant Gram-positive infections. Basic Clin Pharmacol Toxicol 2012; 110: 416-420藥代動(dòng)力學(xué)原理的提示負(fù)荷劑量與藥物分布容積相關(guān)決定達(dá)到目標(biāo)血藥濃度的時(shí)間維

31、持劑量與藥物清除率相關(guān)決定穩(wěn)態(tài)血藥濃度水平PCI術(shù)后氯吡格雷的負(fù)荷劑量和維持劑量Abuzahra M, Pillai M, Caldera A, et al. Comparison of higher clopidogrel loading and maintenance dose on platelet function and es after percutaneous coronary intervention using drug-eluting stents. Am J Cardiol 2008; 102: 401-403Loading 600 mg before PCI and 7

32、5 mg bid x 1 monthLoading 300 mg before PCI and 75 mg qd x 1 monthPCI術(shù)后氯吡格雷的負(fù)荷劑量和維持劑量Gladding P, Webster M, Zeng I, et al. The antiplatelet effect of higher loading and maintenance dose regimens of clopidogrel. The PRINC (Plavix response in coronary intervention) trial. J Am Coll Cardiol Intv 2008;

33、1: 612-619PCI術(shù)后氯吡格雷的負(fù)荷劑量Gladding P, Webster M, Zeng I, et al. The antiplatelet effect of higher loading and maintenance dose regimens of clopidogrel. The PRINC (Plavix response in coronary intervention) trial. J Am Coll Cardiol Intv 2008; 1: 612-619PCI術(shù)后氯吡格雷的維持劑量Gladding P, Webster M, Zeng I, et al.

34、 The antiplatelet effect of higher loading and maintenance dose regimens of clopidogrel. The PRINC (Plavix response in coronary intervention) trial. J Am Coll Cardiol Intv 2008; 1: 612-619結(jié)論與負(fù)荷劑量600 mg相比，PCI后應(yīng)用1200 mg負(fù)荷劑量的氯吡格雷能夠更迅速且更有效地抑制血小板每日150 mg維持劑量更有效地抑制血小板藥代動(dòng)力學(xué)原理的提示負(fù)荷劑量取決于分布容積維持劑量取決于藥物清除率萬(wàn)古霉素的

35、標(biāo)準(zhǔn)用藥劑量肌酐清除率藥物劑量* 60 ml/min10 15 mg/kg q12h115 20 mg/kg q8-12h (45 60 mg/kg/day divided q12h or q8h)240 60 ml/min10 15 mg/kg q12-24h20 40 ml/min5 10 mg/kg q24h10 20 ml/min5 10 mg/kg q24-48h 10 ml/min負(fù)荷劑量10 15 mg/kg IV; 根據(jù)血藥濃度決定后續(xù)藥物劑量血液透析負(fù)荷劑量15 20 mg/kg, 然后僅在血液透析后500 mg IVCVVH10 15 mg/kg q24h* round d

36、ose to 250 mg, 500 mg, 750 mg, 1 g, 1.25 g, 1.5 g, 1.75 g or 2 g (maximum: 2 gm/dose)Higher total daily doses of ycin have been associated with nephrotoxicityFor patients with plicated infections requiring ycin, trough levels of 10-15 mcg/ml are mended.For patients with serious infections due to MRS

37、A (central nervous system infections, endocarditis, ventilator-associated pneumonia, bacteremia or osteomyelitis) , trough levels of 15-20 mcg/ml are mended. ID CONSULT IS MENDED指南中有關(guān)萬(wàn)古霉素負(fù)荷劑量的推薦意見(jiàn)對(duì)于懷疑MRSA感染的重癥患者（如全身性感染，腦膜炎，肺炎或感染性心內(nèi)膜炎），可以考慮給予負(fù)荷劑量25 30 mg/kg（實(shí)際體重）由于應(yīng)用大劑量萬(wàn)古霉素可能引起紅人綜合征及快速過(guò)敏反應(yīng)，應(yīng)當(dāng)延長(zhǎng)輸注時(shí)間至2

38、小時(shí)，并在使用負(fù)荷劑量前使用抗組織胺藥物C-III對(duì)于重癥患者，可以使用負(fù)荷劑量25 30 mg/kg（根據(jù)實(shí)際體重）以迅速達(dá)到萬(wàn)古霉素目標(biāo)谷濃度IIIBLiu C, Bayer A, Cosgrove SE, et al. Clinical practice guideline by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive sum

39、mary. Clin Infect Dis 2011; 52: 285-292Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of ycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists

40、. Am J Health-Syst Pharm 2009; 66: 82-98萬(wàn)古霉素負(fù)荷劑量萬(wàn)古霉素25 mg/kg負(fù)荷劑量按照500 mg/h的速度輸注，對(duì)于危重病患者是安全的，且峰濃度并未達(dá)到危險(xiǎn)范圍給予負(fù)荷劑量1小時(shí)后血藥濃度為26.4 9.3 mg/L，能夠使藥物谷濃度在最初24 48小時(shí)內(nèi)更快超過(guò)8 mg/L，從而確保臨床療效Wang JT, Fang CT, Chen YC, et al. Necessity of a loading dose when using ycin in critically ill patients. J Antimicrob Chemother

41、2001; 47: 246萬(wàn)古霉素負(fù)荷劑量負(fù)荷劑量500 mg(n = 20)負(fù)荷劑量15 mg/kg(n = 20)P value負(fù)荷劑量總劑量(mg)5001147 317 .001根據(jù)體重(mg/kg)7.54 1.5215 .001負(fù)荷劑量后血藥濃度 (mg/L)10.4 2.719.1 7.4 .001平臺(tái)濃度(mg/L)14.9 5.418.5 6.4.06臨床治愈率10/1814/15 .05Mohammedi I, Descloux E, Argaud L, et al. Loading dose of ycin in critically ill patients: 15 m

42、g/kg is a better choice than 500 mg. Int J Antimicrob Angets 2006; 27: 259-262負(fù)荷劑量的重要性：替考拉寧Pea F, Brollo L, Viale P, et al. Teicoplanin therapeutic drug monitoring in critically ill patients: a retrospective study emphasizing the importance of a loading dose. J Antimicrob Chemother 2003; 51: 971-975

43、指南中有關(guān)萬(wàn)古霉素谷濃度的推薦意見(jiàn)對(duì)于MRSA引起的重癥感染如菌血癥，感染性心內(nèi)膜炎，骨髓炎，腦膜炎，肺炎和嚴(yán)重皮膚軟組織感染（如壞死性筋膜炎），推薦將萬(wàn)古霉素谷濃度維持在15 20 g/mLB-II為提高組織通透性，保證萬(wàn)古霉素血藥濃度達(dá)到適當(dāng)?shù)哪繕?biāo)水平，從而改進(jìn)臨床預(yù)后，對(duì)于金黃色葡萄球菌引起的復(fù)雜感染如菌血癥，感染性心內(nèi)膜炎，骨髓炎，腦膜炎和醫(yī)院獲得性肺炎，推薦萬(wàn)古霉素谷濃度維持在15 20 mg/LIIIBLiu C, Bayer A, Cosgrove SE, et al. Clinical practice guideline by the Infectious Diseases

44、Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis 2011; 52: 285-292Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of ycin in adult patients: a consensus review of the American

45、Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health-Syst Pharm 2009; 66: 82-98萬(wàn)古霉素劑量不足非常普遍28張床位內(nèi)科ICU中141名肺炎患者接受萬(wàn)古霉素治療標(biāo)準(zhǔn)萬(wàn)古霉素治療劑量 (15 mg/kg q12h)藥物谷濃度目標(biāo) 15 to 20 mg/L超過(guò)70%患者無(wú)法達(dá)到藥物谷濃度目標(biāo)CrCl 60 ml/min者不能達(dá)標(biāo)比例更高C

46、hung J, Oh JM, Cho EM, et al. Optimal dose of ycin for treating methicillin-resistant Staphylococcus aureus pneumonia in critically ill patients. Anaesth Intensive Care 2011; 39: 1030-1037.危重病患者萬(wàn)古霉素的藥代動(dòng)力學(xué)參數(shù)正常范圍住院患者重癥患者#CL (L/h)4.802.994.82V1 (L/kg)0.65 (0.6 to 0.7)0.5 to 0.6*0.7 to 0.85*0.6750.82, 2

47、.49V2 (L/kg)0.732* dehydrated* overhydrated# age 61 years, body weight 71 kg; serum creatinine 1 mg/dL; serum creatinine 1 mg/dL CL (L/h) = CrCl x 0.048; CrCl = 100 ml/minThomson AH, Staatz CE, Tobin CM, et al. Development and evaluation of ycin dosage guidelines designed to achieve new target concentrations. J Antimicrob Chemother 2009; 63: