1、整理課件1革蘭陽性球菌感染與達托霉素的臨床實踐上海交通大學醫學院附屬瑞金醫院院感科 臨床微生物科倪語星整理課件2一、達托霉素（一、達托霉素（Daptomycin）的殺菌特性的殺菌特性整理課件33環脂肽類抗生素環脂肽類抗生素Cyclic lipopeptide Streptomyces roseosporus 的天然發酵物分子式 C72H101N17O26分子量分子量 1620.67無菌、無熱原淡黃色淺棕色塊狀凍晶賦形劑為NaOH (調整pH值)Clinical Infectious Diseases 2004;38:994-1000整理課件44Anti MRSA 比比較較 分分類類Brand

2、NameCubicin Tygacil Zyvox Vancocin Targocid DaptomycinDaptomycinTigecycline Tigecycline Linezolid Linezolid VancomycinVancomycinTeicoplanin Teicoplanin US Launch 2003200520001964noneClasscyclic lipopeptide glycylcycline oxazolidinoneglycopeptideglycopeptidecidal/staticrapidly cidal static staticslow

3、ly cidal slowly cidal Location of activityCell MembraneRibosomal subunitRibosomal RNA subunitCell WallCell Wall整理課件5Daptomycin達托霉素作用機制為插入革蘭陽性菌細胞膜內，由于細菌膜結構的不同，對革蘭陰性菌無作用。達托霉素具有殺菌性，相比其他抗菌藥物，達托霉素對于靜止期細菌的殺菌率有顯著性升高。達托霉素對附著于醫療裝置表面及生物被膜的細菌有顯著有效性。Pharmacology 2008;81:7991.整理課件6達托霉素的快速殺菌活性- in vitro 對于金葡菌，對于金

4、葡菌，2-4倍倍MIC的達托霉素達到殺菌作用（降低的達托霉素達到殺菌作用（降低3log)只只需要需要1小時左右；小時左右；對于對于VRE，則需要，則需要2-6小時小時Clinical Microbiology Newsletter:Vol. 24, No. 5; March 1,2002整理課件77024681012140122436486072Time (hours)CFU/g (log10)對靜止生長期金黃色葡萄球菌有快速殺菌活性Pharmacodynamic model utilizing simulated endocardial vegetations (Tedesco and Ry

5、bak, ICAAC 2003)對照對照達托霉素達托霉素利奈唑胺利奈唑胺奈夫西林奈夫西林 萬古霉素萬古霉素整理課件8Rapid Bactericidal Activity of Daptomycin Against MRSA Peritonitis in Healthy MiceMortin LI, LI T, Van Praagh ADG, Zhang S, Zhang X-X, Alder JD. Rapid bactericidal activity of daptomycin against methicillin-resistant and methicillin-susceptib

6、le Staphylococcus aureus peritonitis in mice as measured with bioluminescent bacteria. Antimicrob Agents Chemother. 2007;51:1787-1794. 整理課件9Rapid Bactericidal Activity of Daptomycin Against MRSA Peritonitis in Neutropenic MiceMortin LI, LI T, Van Praagh ADG, Zhang S, Zhang X-X, Alder JD. Rapid bacte

7、ricidal activity of daptomycin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus peritonitis in mice as measured with bioluminescent bacteria. Antimicrob Agents Chemother. 2007;51:1787-1794. 整理課件10體外超微結構電鏡顯示體外超微結構電鏡顯示:達托霉素不會使達托霉素不會使MSSA/MRSA的死亡后崩解的死亡后崩解A) 沒有抗生素(B) 達托霉素

8、8 mg/L，1 hC) 達托霉素 8 mg/L，24 h.Wale LJ, et al., J Med Microbiol. 1989;30(1):45-49.10A) 沒有抗生素(B) 達托霉素 8 mg/L，4 hC) 達托霉素 8 mg/L，24 hMSSAMRSA整理課件11Biofilms 細菌生物膜常見于植細菌生物膜常見于植入導管，假體等的表面入導管，假體等的表面ASM Microbe Libraryhttp:/www.microbe/ 整理課件12達托霉素對于形成生物被膜的達托霉素對于形成生物被膜的導管葡萄球菌感染具有很強的的穿透力導管葡萄球菌感染具有很強

9、的的穿透力ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, May 2007, p. 16561660整理課件13達托霉素的殺菌速度很快Raad, et al. Antimicrobial Agents and Chemotherapy, 2007, 51:16561660整理課件14二、指南推薦二、指南推薦GUIDELINES整理課件15美國IDSA MRSA 感染治療指南Liu et al. Clin Infect Dis 2011 Jan 4整理課件16關于達托霉素的推薦要點 達托霉素作為MRSA血流感染和自身瓣膜感染性心內膜炎的治療方案, 證據等級及推薦度(

10、 AI)高于萬古霉素( AII) 達托霉素在成人復雜性SSTI治療推薦中與萬古霉素、利奈唑胺等藥物為同等級( AI) 骨髓炎和化膿性關節炎治療中與萬古霉素、利奈唑胺等藥物同等級( BII)整理課件17IDSA MRSA 指南: 患有菌血癥或自體瓣膜感染性心內膜炎的成人1 推薦的治療持續時間 非復雜性菌血癥 至少 2 周 復雜性菌血癥 4-6 周 自體瓣膜感染性心內膜炎 6 周患有患有菌血癥或自體瓣膜感染性心內膜炎的成人的抗菌治療選擇匯總治療治療成人用量成人用量等級等級*評論評論萬古霉素15-20 mg/kg/劑 IV q8-12hA-II不建議在萬古霉素中加入慶大霉素(A-II)或利福平(A-

11、I) 達托霉素6 mg/kg/劑 IV QDA-I一些專家建議使用更高劑量，8-10 mg/kg/天 IV QD (B-III)*推薦度和證據等級分類1. Liu C, Bayer A, Cosgrove SE et al. Clinical practice guidelines by the Infectious Diseases Society of America for the 藥劑 of methicillin-resistant Staphylococcus aureus infections in 成人s and children. Clin Infect Dis. 2011

12、Jan 4 Epub ahead of print 萬古霉素是此類治療的主流治療藥物 達托霉素是萬古霉素的替代治療藥物整理課件18三、臨床實踐三、臨床實踐 REVIEWS整理課件19（一）金葡菌感染經驗性用藥（一）金葡菌感染經驗性用藥19 - do not use + use only as alternative + good drug for this indication + very good drug for this indication Minerva Anestesiol 2011；77：821-827整理課件20（二）自體瓣膜心內膜炎的治療（二）自體瓣膜心內膜炎的治療Dona

13、ld P. Levine1，Kenneth C. Lamp DAPTOMYCIN FOR NATIVE VALVE ENDOCARDITIS: EXPERIENCE FROM A REGISTRY 10th International Symposium on Modern Concepts in Endocarditis and Cardiovascular Infections Naples, Italy, April 26-28, 2009整理課件21結果療效不同病原菌感染的治療成功率相似不同病原菌感染的治療成功率相似自體瓣膜心內膜炎的達托霉素治療成功率為自體瓣膜心內膜炎的達托霉素治療成

14、功率為84%整理課件22（三）（三）VANCOMYCIN MIC 1整理課件23Evaluation of a Clinical Pathway for the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia (MRSAB) with an MIC of 1 mg/L to Vancomycin *Ravina Kullar1, Susan L. Davis1, Jason M. Pogue2, Jing J. Zhao2; Donald P. Levine2,3, Keith K. Kaye2,3; Michael J.