抗菌治療進(jìn)展

1、關(guān)于抗菌治療進(jìn)展第一張，PPT共六十一頁，創(chuàng)作于2022年6月2OUTLINEMRSA的臨床重要性MRSA的藥物敏感性及變遷MRSA感染的抗菌治療第二張，PPT共六十一頁，創(chuàng)作于2022年6月問題1、MRSA的臨床重要性如何？耐藥革蘭陰性菌給臨床帶來的問題較革蘭陽性菌更大，如鮑曼不動桿菌革蘭陽性菌中，MRSA的臨床重要性最大第三張，PPT共六十一頁，創(chuàng)作于2022年6月3.2 million bacterial isolates from 300 clinical lab 19982005 across the United StatesStyers D, et al. Ann Clin Mi

2、crobiol Antimicrob 2006, 5:2.Staphylococcus aureusEscherichia coliEnterococcus spp.Coagulase-negative staphylococciPseudomonas aeruginosaKlebsiella pneumoniaeProteus mirabilisEnterobacter cloacaeSerratia marcescensAcinetobacter baumanniEscherichia coliStaphylococcus aureusEnterococcus spp.Pseudomona

3、s aeruginosaCoagulase-negative staphylococciKlebsiella pneumoniaeProteus mirabilisEnterobacter cloacaeStreptococcus pneumoniaeCitrobacter freundiiPercentage of all bacterial isolates encounteredPercentage of all bacterial isolates encounteredTop ten pathogens among inpatientsTop ten pathogens among

4、outpatients1.51.62.93.16.110.312.712.717.318.805101520253035401.01.01.54.26.26.36.58.814.938.60510152025303540S. aureus is a leading cause of bacterial infections in hospitals and community in the US第四張，PPT共六十一頁，創(chuàng)作于2022年6月中國革蘭陽性菌菌種分布 細(xì)菌株數(shù) 金葡菌600035.6 腸球菌屬459327.2 凝固酶陰性葡萄球菌335319.9 （血液腦脊液等無菌體液） 肺炎鏈球菌

5、11246.7 -溶血性鏈球菌12297.3 草綠色鏈球菌（血液及無菌體液）2081.2 其他3652.2 合計(jì)16872100.0CHINET 2011金葡菌是臨床最常見的革蘭陽性菌第五張，PPT共六十一頁，創(chuàng)作于2022年6月MRSA可引起各類感染 骨髓炎食物中毒皮膚燙傷綜合征T中毒休克綜合征膿皰病癤肺炎眼內(nèi)炎心內(nèi)膜炎蜂窩織炎第六張，PPT共六十一頁，創(chuàng)作于2022年6月Annual Death Rates in the United StatesSelected Infectious DiseasesNo. of patients diedBoucher HW and Corey GR.

6、 Clin Infect Dis 2008;46:S344-9.MRSA感染的死亡病例數(shù)高于AIDS的死亡病例數(shù)第七張，PPT共六十一頁，創(chuàng)作于2022年6月8S. aureus is the most common pathogen of HAP (n=656)Percentage(%)S aureusMRSAP aeruginosaE coliK pneumoniaeEnterococcus sppE. faecalisCandida sppC. albicansCoNSAcinetobacter sppA. baumanniiEnterobacter sppE. cloacaeS. ma

7、rcescensS. maltophiliaC. freundiiOthersKim JM. Am J Infect Control 2000;28:454-8. 91% of S. aureus were MRSA第八張，PPT共六十一頁，創(chuàng)作于2022年6月9MRSA is the third most common pathogen of HAP in ChinaA multi-center survey conducted in 12 hospitals in China from 2008 to 2010 to know the incidence and causative pat

8、hogens of HAP.Liu YN, unpublished data by personal communicationPercentage(%)A. baumannii P. aeruginosaS. aureusK. pneumoniaeC. albicansS. maltophiliaE. coliE. cloacaeC. Tropical CoNS The incidence of HAP varies from 0.9-4.1% in different hospitals in ChinaA. fumigatus第九張，PPT共六十一頁，創(chuàng)作于2022年6月Doern GV

9、 et al: Diagn Microbiol Infect Dis 1999;34:65Brook I: Int J Surg 2008;6:328Chira S, Miller LG: Epidemiol Infect 2010;138:313Gram-positive organisms predominate (60-70%)S. aureus - 48% in one studyGroup A -hemolytic streptococci - 26%Gram-negative organisms involved in 25-35% of infectionsAnaerobic a

10、nd fungal organisms are uncommonPolymicrobial infections are encountered:Especially with deeper soft tissue infectionsMicrobiology in Skin/Soft Tissue Infections金葡菌是皮膚軟組織感染的最常見病原菌第十張，PPT共六十一頁，創(chuàng)作于2022年6月11OUTLINEMRSA的臨床重要性MRSA的藥物敏感性及變遷MRSA感染的抗菌治療第十一張，PPT共六十一頁，創(chuàng)作于2022年6月Prevalence of MRSA and MRCNS in

11、 Shanghai region since 1999第十二張，PPT共六十一頁，創(chuàng)作于2022年6月問題2、MRSA對萬古霉素的耐藥性如何？ 是否存在MIC漂移（MIC creep）？第十三張，PPT共六十一頁，創(chuàng)作于2022年6月MSSA(2954株)與MRSA(3033株)的耐藥率（%）CHINET 2011耐藥監(jiān)測數(shù)據(jù)顯示，MRSA對萬古霉素、利奈唑胺100敏感第十四張，PPT共六十一頁，創(chuàng)作于2022年6月15Twelve VRSA (Vancomycin resistant S. aureus) reported in the USTwelve cases from USAPosi

12、tive for the vanA geneMedian vancomycin MIC: 512 mg/LAll patients had prior MRSA colonization or infectionsAll had severe underlying factorsAAC 2009; 53: 4580-7第十五張，PPT共六十一頁，創(chuàng)作于2022年6月16Five VRSA reported in AsiaIndia: 3 strains 2 strains: vancomyicn MIC 32 or 64 mg/L, vanA negative in addition, fou

13、nd 6 VISA strains (Tiwari HK, BMC Infect Dis 2006; 6: 156)One VRSA vancomycin MIC64 mg/L, vanA positive (Saha B, et al. J Med Microbiol 2008; 57, 7279)Iran: 2 strainsOne isolate had a vancomycin MIC of 64 mg/LOther one had a vancomycin MIC of 512 mg/L and vanA positive ( Aligholi M, et al. Med Princ

14、 Pract 2008; 17(5): 432)第十六張，PPT共六十一頁，創(chuàng)作于2022年6月17異質(zhì)性萬古霉素中介金葡菌（hVISA）在中國的發(fā)生情況1012株MRSA于2002-7年（主要為05-07）分離自14個(gè)城市檢測方法：含藥平皿及MET初篩，菌群分析策略-曲線下面積方法確認(rèn)nhVISA 血培養(yǎng)20013.1(26/199)VISA 1 (萬古 MIC 4mg/L)非血培養(yǎng)81215.7（128/812）2007年分離自14個(gè)城市315株MRSA，hVISA 9.5(30/315) (陳宏斌，中華檢驗(yàn)醫(yī)學(xué)雜志 2009; 32(11): 1223-7)Sun W, AAC 2009

15、; 53(9): 3642-9第十七張，PPT共六十一頁，創(chuàng)作于2022年6月 How to detect VISA and hVISA ?第十八張，PPT共六十一頁，創(chuàng)作于2022年6月19Clinical Infectious Diseases 2007; 44:153642VISA was identified as S“ by disc diffusion17mm zone “S”MIC 8ug/ml “I”Disc diffusion and E-TestE-Test: MIC 2, but disc diffusion: for “S”E-Test: MIC =2, but dis

16、c diffusion: for “S”E-Test: MIC2, but disc diffusion: for “S”MIC 8ug/ml “I”17mm zone “S”MIC 8ug/ml “I”17mm zone “S”MIC 8ug/ml “I”17mm zone “S”MIC 8ug/ml “I”17mm zone “S”MIC 8ug/ml “I”VISA strains (vanco MIC 4-8 ) hVISA (vanco MIC 1-2 ) CAN NOT be detected by disk diffusion method第十九張，PPT共六十一頁，創(chuàng)作于202

17、2年6月20MIC testing is recommended by CLSI to determine vancomycin susceptibility for MRSA since 2009* BHI+6g/ml vancomycin* send to reference lab第二十張，PPT共六十一頁，創(chuàng)作于2022年6月21Comparison of laboratory detection methods of hVISAMethodSensitivitySpecificityVancomycin broth MIC11%100%BHIA + BHIA6V48 h, 4.512

18、%48 h, 68100%MHA + MHA5T48 h, 6579%48 h, 3595%MHA + MHA5T48 h, 98%48 h, 53%BHIA +Vancomycin 5g/ml，10l of a 0.5 McFarlandstandard suspension48 h, 120%48 h, 5999%Simplified PAP*48 h, 71%48 h, 88%Macromethod Etest (MET)48 h, 6998.5%48 h, 8994%Etest GRD24 h, 7077%48 h, 9394%24 h, 98100%48 h, 8295%Benjam

19、in P. CLINICAL MICROBIOLOGY REVIEWS. 2010; 23:99-139.hVISA can not be detected by routine methodsPopulation analysis profile (PAP) is “gold standard”, but it is labor-intensive and impractical for clinical lab.Testing for hVISA is not routinely recommended 第二十一張，PPT共六十一頁，創(chuàng)作于2022年6月Vancomycin MIC cre

20、ep：地區(qū)差異22Journal of Antimicrobial Chemotherapy (2007) 60, 788794第二十二張，PPT共六十一頁，創(chuàng)作于2022年6月23全球九國10年（2001-2010）分離MRSA萬古霉素MIC幾何均數(shù)在1mg/L左右(0.661.13)Reynolds R, ECCMID 2012, P1215 第二十三張，PPT共六十一頁，創(chuàng)作于2022年6月Vancomycin Susceptibility in MRSA Over 10 Years: MIC Decrease After a Transient CreepVancomycin MIC

21、mg/L: n (%)Year (n)0.5-0.751.001.502.003.0-4.0Means SDVanco. use for MRSA02-03 (186)06 (3.2)86 (46.2)85 (45.7)9 (4.8)1.78 0.3995.0%05-06 (184)1 (0.5)2 (1.1)95 (51.6)70 (38.0)16 (8.7)1.82 0.4791.0%08-09 (172)00110 (64.0)61 (35.5)1 (0.6)1.69 0.2693.2%10-12 (135)2 (1.5)15 (10.9)97 (70.8)20 (14.6)1 (0.7

22、8)1.52 0.3093.5%ICAAC 2012. C2-1391 R. Khatib, Grosse Pointe Woods, MI 677 isolates tested. Van MIC was stable between 2002-3 and 2005-6, increased in 2008-9 and decreased in 2010-2The reason for this decrease is uncertain. It may be due to reduced use of V or higher drug concentrations. The targete

23、d V trough levels were increased in early 2010 to 15-20 g/L 第二十四張，PPT共六十一頁，創(chuàng)作于2022年6月25OUTLINEMRSA引起的常見感染MRSA的藥物敏感性及變遷MRSA感染的抗菌治療第二十五張，PPT共六十一頁，創(chuàng)作于2022年6月問題3、目前臨床應(yīng)用的治療MRSA感染的抗菌藥主要有哪些？各有什么優(yōu)缺點(diǎn)？第二十六張，PPT共六十一頁，創(chuàng)作于2022年6月抗MRSA的最主要抗菌藥物27萬古霉素Vancomycin利奈唑胺Linezolid達(dá)托霉素Daptomycin類型糖肽類噁唑烷酮類環(huán)脂肽類抗菌類型殺菌劑（葡萄球菌）抑

24、菌劑（腸球菌/葡萄球菌）快速殺菌劑（革蘭陽性菌）抗菌譜G(+)G(+)G(+)作用部位細(xì)胞壁核糖體 RNA 亞基細(xì)胞膜第二十七張，PPT共六十一頁，創(chuàng)作于2022年6月萬古霉素的優(yōu)點(diǎn)與缺點(diǎn)優(yōu) 點(diǎn)臨床使用近50年，革蘭陽性菌對其仍高度敏感治療革蘭陽性菌感染最為經(jīng)典的藥物臨床適應(yīng)證最廣缺 點(diǎn)MRSA敏感性下降問題組織濃度不良反應(yīng)第二十八張，PPT共六十一頁，創(chuàng)作于2022年6月萬古霉素利奈唑胺達(dá)托霉素復(fù)雜性皮膚軟組織感染血流感染與自身瓣膜心內(nèi)膜炎人工瓣膜心內(nèi)膜炎(聯(lián)合慶大、利福平)肺炎骨髓炎 (超適應(yīng)證） (超適應(yīng)證）植入物相關(guān)骨髓炎、關(guān)節(jié)炎 (超適應(yīng)證） (超適應(yīng)證）腦膜炎，腦膿腫等CNS感染(

25、超適應(yīng)證）不同MRSA感染的抗菌藥物選擇Liu C, Clin Infect Dis 2011; 52(3):2852011 IDSA MRSA指南萬古霉素的臨床適應(yīng)證最廣第二十九張，PPT共六十一頁，創(chuàng)作于2022年6月萬古霉素治療藥物監(jiān)測（TDM）相關(guān)問題監(jiān)測血清谷濃度監(jiān)測給藥劑量最準(zhǔn)確、實(shí)用；應(yīng)在達(dá)到穩(wěn)態(tài)后采集標(biāo)本（第4-5次給藥前） ；并非所有患者需要血藥濃度監(jiān)測；監(jiān)測谷濃度對象：腎功能損害；肥胖；表觀分布容積波動；第三十張，PPT共六十一頁，創(chuàng)作于2022年6月31Trough serum vancomycin concentrations always be maintained

26、at 10 mg/L to avoid the development of resistance (BIII)To improve clinical outcomes of hospital-acquired pneumonia caused by S. aureus, trough serum vancomycin concentrations of 1520 mg/L are recommended (Note: much higher than former concentration of 5-10 mg/L) (BIII)To achieve rapid attainment of

27、 this target concentration for seriously ill patients, a loading dose of 2530 mg/kg )(1.5-1.8 g)(based on actual body weight) can be considered. (BIIITrough serum vancomycin concentrations in that range should achieve an AUC/MIC of 400 for most patients if the MIC is 580, 腸球菌感染 638，預(yù)測95患者可達(dá)臨床有效第三十二張

28、，PPT共六十一頁，創(chuàng)作于2022年6月糖肽類的耳腎毒性問題在上市之初，因純度的問題，毒性較明顯純度提高后，耳腎毒性發(fā)生率低長療程用藥需注意藥物熱的出現(xiàn)可能第三十三張，PPT共六十一頁，創(chuàng)作于2022年6月利奈唑胺的優(yōu)點(diǎn)與缺點(diǎn)優(yōu) 點(diǎn)新類別抗菌藥對VRE、VISA、hVISA等具抗菌活性臨床適應(yīng)證較廣同時(shí)有靜脈及口服制劑缺 點(diǎn)抑菌劑靜脈導(dǎo)管相關(guān)血流感染療效問題耐藥性出現(xiàn)較快骨髓抑制第三十四張，PPT共六十一頁，創(chuàng)作于2022年6月萬古霉素利奈唑胺達(dá)托霉素復(fù)雜性皮膚軟組織感染血流感染與自身瓣膜心內(nèi)膜炎人工瓣膜心內(nèi)膜炎(聯(lián)合慶大、利福平)肺炎骨髓炎 (超適應(yīng)證） (超適應(yīng)證）植入物相關(guān)骨髓炎、關(guān)節(jié)炎

29、 (超適應(yīng)證） (超適應(yīng)證）腦膜炎，腦膿腫等CNS感染(超適應(yīng)證）不同MRSA感染的抗菌藥物選擇Liu C, Clin Infect Dis 2011; 52(3):2852011 IDSA MRSA指南利奈唑胺的臨床適應(yīng)證較廣第三十五張，PPT共六十一頁，創(chuàng)作于2022年6月新類別抗菌藥研發(fā)困難近年開發(fā)新類別抗菌藥少利奈唑胺(linezolid)：惡唑烷酮類(oxazolidinones)達(dá)托霉素(daptomycin): 脂肽類現(xiàn)有類別藥物的改進(jìn)替利霉素(telithromycin)：酮內(nèi)酯類ketolides, 為大環(huán)內(nèi)酯類紅霉素A的衍生物替加環(huán)素(tigecycline)：甘氨酰環(huán)素類

30、glycylcyclines為四環(huán)素類米諾環(huán)素的衍生物特拉萬星(telavancin)：脂糖肽類lipoglycopeptides，為萬古霉素的衍生物第三十六張，PPT共六十一頁，創(chuàng)作于2022年6月利奈唑胺對革蘭陽性菌具良好抗菌作用致病菌菌株數(shù)MIC90(g/ml)MIC范圍(g/ml)敏感率(%)金黃色葡萄球菌324020.5-4100 MRSA109220.5-4100 MSSA214820.5-4100凝固酶陰性葡萄球菌74820.5-499.6腸球菌86420.25-899.3 VRE8620.5-897.7肺炎鏈球菌65510.12-2100草綠色鏈球菌21610.06-2100-

31、溶血性鏈球菌39810.25-2100Jones RN et al. Diagnostic Microbiology and Infectious Disease . 2009;65:404413.2008年對24個(gè)國家64個(gè)醫(yī)學(xué)中心收集的6121株G+球菌進(jìn)行的耐藥監(jiān)測結(jié)果第三十七張，PPT共六十一頁，創(chuàng)作于2022年6月利奈唑胺不推薦用于導(dǎo)管相關(guān)血流感染2007年FDA向醫(yī)生發(fā)出警告治療導(dǎo)管相關(guān)感染的研究表明2 利奈唑胺治療首次用藥后84天內(nèi)的死亡率21.5%(78/363) ，而對照組為16.6%(58/363)1,Wilcox MH, Tack KJ,Bouza E,et al. Co

32、mplicated skin and skin structure infections and Catheter Related Bloodstream Infections Noninferiority of Linezolid in Phase 3 Sutdy.Clinical Infectious Disease 2009, 48:203-212.2,FDA Alert 3/18/2007.第三十八張，PPT共六十一頁，創(chuàng)作于2022年6月美國 Leader program 2004-2010耐利奈唑胺的金葡菌發(fā)生率Diagnostic Microbiology and Infecti

33、ous Disease 74 (2012) 5461耐藥率 (%)N=21642全球監(jiān)測顯示，MRSA對利奈唑胺的耐藥率低第三十九張，PPT共六十一頁，創(chuàng)作于2022年6月Clinical outbreak of linezolid-resistant Staphylococcus aureusin an intensive care unit in Spain (Hospital Clinico San Carlos)Snchez Garca M, JAMA. 2010; 303(22):2260-4第四十張，PPT共六十一頁，創(chuàng)作于2022年6月 Mechanism of linezoli

34、d resistanceMutations in domain V of 23S rRNAMutations in rplC (ribosomal protein L3) and rplD (L4)Mediated by Cfr methyltransferaseUnknown mechanism第四十一張，PPT共六十一頁，創(chuàng)作于2022年6月問題4、治療MRSA肺炎，利奈唑胺是否優(yōu)于萬古霉素？第四十二張，PPT共六十一頁，創(chuàng)作于2022年6月57.654.883.380.146.644.969.967.8020406080100PP at EOSMITT at EOSPP at EOTMI

35、TT at EOTProportion of patients with successful response (%)LinezolidVancomycin P = 0.04295%CI 0.5-21.6P = 0.04995%CI 0.1-19.8P = 0.002 P = 0.004n=165*n=7n=180*n=3n=186*n=2n=186 *n=38n=201*n=23n=214*n=10n=205*n=19n=174*n=2Primary endpointSecondary endpoint* Number of excluded patientsZephyr study: l

36、inezolid is superior than vancomycin in the treatment of MRSA pneumoniaWunderink RG, CID 2012; 54: 621-9第四十三張，PPT共六十一頁，創(chuàng)作于2022年6月60 Days Kaplan-Meier Survival rates were similar between two groups for mITT PopulationSurvival Distribution Function0.20.40.60.8010204060Time (Days)LinezolidLinezolid Cen

37、sorVancomycinVancomycin Censor* * * 10305094 subject deaths ( 15.7%) in linezolid arm100 subject deaths (17.0%) in vancomycin arm Controversy: is linezolid really better than vancomycin?第四十四張，PPT共六十一頁，創(chuàng)作于2022年6月57.654.883.380.146.644.969.967.8020406080100PP at EOSMITT at EOSPP at EOTMITT at EOTPropo

38、rtion of patients with successful response (%)LinezolidVancomycin P = 0.04295%CI 0.5-21.6P = 0.04995%CI 0.1-19.8P = 0.002 P = 0.004n=165*n=7n=180*n=3n=186*n=2n=186 *n=38n=201*n=23n=214*n=10n=205*n=19n=174*n=2Primary endpointSecondary endpoint*Unknown excluded pts from analysis A large number of mITT

39、 patients excluded from the statistic populationControversy : is linezolid really better than vancomycin?第四十五張，PPT共六十一頁，創(chuàng)作于2022年6月 Higher proportion of cases with MRSA bacteremia and mechanical ventilation in the vancomycin armCharacteristicBaseline Clinical CharacteristicsVancomycin armNo. (%)Linez

40、olid armNo. (%)Mechanical ventilation 130(73.9)115(66.9 )Bacteremia20(10.8)9(5.2)The baseline clinical characteristics of vancomycin arm are seems to be more complicated and severeControversy: is linezolid really better than vancomycin?第四十六張，PPT共六十一頁，創(chuàng)作于2022年6月47針對MRSA醫(yī)院肺炎的薈萃分析提示 萬古霉素的臨床療效與利奈唑胺相仿Wal

41、key AJ, CHEST 2010; DOL 1378/1556. RR(95%CI)1.09 (0.82-1.44)1.23 (0.72-2.07)0.97 (0.78-1.19)1.02 (0.89-1.16)0.93 (0.63-1.36)0.93 (0.39-2.24)1.17 (0.73-1.87)1.41 (0.64-3.08)1.02 (0.93-1.12)臨床成功例數(shù)/總數(shù)322/84171/20320/50114/32151/5723/4711/5119/3813/74利奈唑胺糖肽類62/19326/49111/30252/5930/576/2618/429/72304/8

42、00研究/亞組研究Rubenstein 2001Stevens 2002Wunderink 2003Wilcox 2004Cepeda 2004Kohno 2007Lin 2007Wunderink 2008異質(zhì)性 X2 =2.20，p=0.95，I2=0%總體療效，p=0.6350.20.512利于糖肽類利于利奈唑胺薈萃分析第四十七張，PPT共六十一頁，創(chuàng)作于2022年6月達(dá)托霉素的優(yōu)點(diǎn)與缺點(diǎn)優(yōu) 點(diǎn)新類別抗菌藥快速殺菌作用對VRE、VISA、hVISA等具抗菌活性缺 點(diǎn)無肺炎適應(yīng)證價(jià)格較高CPK升高在中國的問題：血培養(yǎng)陽性率低第四十八張，PPT共六十一頁，創(chuàng)作于2022年6月Bacteria

43、l Growth Phases:達(dá)托霉素對靜止期細(xì)菌也具殺菌作用Stationary-phase bacteria: are non-dividing and metabolically arrested.Associated with persistent infections (endocarditis and osteomyelitis) Associated with biofilm-related infections (catheters, grafts, and foreign bodies) The mechanism of action of many bactericida

44、l antibiotics requires ongoing cell division (log phase)Normally bactericidal antibiotics (e.g. , beta-lactams) may display limited activity against stationary phase cellsMascio et al., AAC 2007 p. 42554260 Vol. 51, No.12. 第四十九張，PPT共六十一頁，創(chuàng)作于2022年6月TissueVancomycinLinezolidDaptomycinBone7%-13%60%117%

45、CSF0%-18%70%5-6%Lung alveolar11%-17%100%-450%10%Blister fluid20%-30%104%70%Muscle30%94%Peritoneal fluid20%61%40%Blood clot tissue70%Drug Penetration: % Tissue/Serum達(dá)托霉素在多數(shù)組織的濃度較高第五十張，PPT共六十一頁，創(chuàng)作于2022年6月萬古霉素利奈唑胺達(dá)托霉素復(fù)雜性皮膚軟組織感染血流感染與自身瓣膜心內(nèi)膜炎人工瓣膜心內(nèi)膜炎(聯(lián)合慶大、利福平)肺炎骨髓炎 (超適應(yīng)證） (超適應(yīng)證）植入物相關(guān)骨髓炎、關(guān)節(jié)炎 (超適應(yīng)證） (超適應(yīng)證）

46、腦膜炎，腦膿腫等CNS感染(超適應(yīng)證）不同MRSA感染的抗菌藥物選擇Liu C, Clin Infect Dis 2011; 52(3):2852011 IDSA MRSA指南第五十一張，PPT共六十一頁，創(chuàng)作于2022年6月Daptomycin Outcomes in Patients with Severe Sepsis due to Staphylococcal Bacteremia with Vancomycin MICs of 2 mg/L Success by Subgroup (%)Success (%)Failure (%)Overall (n=100)8614MRSA (n=

47、73)8812MSSA (n=8)8812CoNS (n=19)7921DAP monotherapy (n=52)8812Prior vancomycin failure (n=27)7822Septic shock (n=15)6733100 pts were included in the efficacy population (15 of which had septic shock) 72 pts received vancomycin prior to DAP, and of those, 27 (38%) failed therapy. ICAAC 2012. K-1635 K. Holloway, MA第五十二張，PPT共六十一頁，創(chuàng)作于2022年6月克林霉素（Clindamycin)FDA批準(zhǔn)治療葡萄球菌感染；皮膚軟組織、骨骼等組織濃度高（不包括CSF）；成功治療兒童侵襲性CA-MRSA感染（骨髓炎、關(guān)節(jié)炎、肺炎等）；妊娠用藥分類B；抑菌劑，不用于血管內(nèi)感染（BSI、IE）；誘導(dǎo)耐藥，HA-MRS