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1、 MRSA感染的抗菌治疗 Date1McDonald LC. Clin Infect Dis. 2006;42:S65-S71.Nosocomial infectionCommunity-acquired infectionPenicillinase-producing S aureus02550751001940196019802000YearResistant isolates (%)Methicillin-resistant S aureus02550751001940196019802000YearResistant isolates (%)Progression of resista
2、nt Staphylococcus aureusA similar trend in the increase in nosocomial infectionscaused by antimicrobial-resistant S aureus isolates can be observed in community-acquired infectionsDate2Emergence of resistant pathogensEmergence of resistant pathogensIncrease in Increase in nosocomialnosocomial S S au
3、reusaureus bacteremiabacteremia predominantly due to the increase in MRSA in the UKpredominantly due to the increase in MRSA in the UKWyllie D, et al. BMJ. 2006;333:281-284.Cohort study in Oxfordshire, UK; MSSA = methicillin-sensitive Staphylococcus aureus a Per 100,000 admissions; b P .2.Year400500
4、3002001501005019971999200020012002200320041998Cases of S aureusBacteremia*Year4005003001501005019971999200020012002200320041998Cases of S aureusBacteremiaaAll Nosocomial S aureus BacteremiabYear4005003002001501005019971999200020012002200320041998Cases of S aureusBacteremia*Year4005003002001501005019
5、971999200020012002200320041998Cases of S aureus BacteremiaaMSSA MRSAcbDate34Date4HA-MRSA StrainsHA-MRSA Strainsn nHigh local prevalenceHigh local prevalencen nHistory of MRSA infection History of MRSA infection or colonizationor colonizationn nClose contact with Close contact with infected individua
6、linfected individualn nExtended hospitalizationExtended hospitalizationn nResident of nursing home or Resident of nursing home or long-term-care facilitylong-term-care facilityn nInvasive devicesInvasive devicesn nDialysisDialysisn nCatheterizationCatheterizationn nEnteralEnteral feeding feedingn nR
7、ecent antibiotic useRecent antibiotic useRisk factors for infection with MRSARisk factors for infection with MRSACA-MRSA StrainsCA-MRSA Strainsn nHigh local prevalenceHigh local prevalencen nHistory of MRSA infection History of MRSA infection or colonizationor colonizationn nClose contact with Close
8、 contact with infected individualinfected individualn nCrowded and/or Crowded and/or unsanitary conditionsunsanitary conditionsn nPrisonPrisonn nMilitary campMilitary campn nDepressed immune systemDepressed immune systemn nParticipation in contact Participation in contact sportssportsn nSharing athl
9、etic Sharing athletic equipment/towelsequipment/towelsn nIntravenous drug abuseIntravenous drug abuse1. MRSA Infection. MayoC 2007. Availabe at: http:/ 2. Graffunder EM, Venezia RA. J Antimicrob Chemother. 2002;49:999-1005. 3. Safdar N, Maki DG. Ann Intern Med. 2002;136:834-844. 4. Moran GJ, et al.
10、N Engl J Med. 2006;355:666-74. Date5Date6MRSA感染的危害n nMRSAMRSA感染可能感染可能n n增加死亡增加死亡风险风险1 1n n增加患病率增加患病率2,32,3n n延延长长住院住院时间时间2,32,3n n增加住院增加住院费费用用1,2,41,2,41. Rubin RJ, et al. Emerg Infect Dis. 1999;5:9-17. 2. Carbon C. J Antimicrob Chemother. 1999;44(suppl A):31-36. 3. The Brooklyn Antibiotic Resistanc
11、e Task Force. Infect Control Hosp Epidemiol. 2002;23:106-108. 4. Abramson MA et al. Infect Control Hosp Epidemiol. 1999;20:408-411. 5. Cosgrove SE et al. Clin Infect Dis. 2003;36:53-59.死亡率相关性比死亡率相关性比较较较较5 5：MRSA MRSA vsvs MSSAMSSA比比值值值值比比研究研究MSSA:methicillinMSSA:methicillin-sensitive staphylococcus
12、-sensitive staphylococcus aureusaureusDate78Date89Date910Date1011Date1112Date12VAPVAP致病菌与致病菌与经验经验经验经验 性抗生素治性抗生素治疗错误疗错误疗错误疗错误 的的 比例比例铜绿假单胞菌MRSA 不动杆菌属Kollef MH Clinical Inf Diseases 31 Suppl 4:131-8, Sept 2000Date13肺炎肺炎( (包括包括VAP)VAP)需要覆盖需要覆盖MRSAMRSA的考的考虑虑虑虑n n流感、糖尿病、流感、糖尿病、颅脑颅脑颅脑颅脑 外外伤伤伤伤、肾肾肾肾衰、昏迷并衰、
13、昏迷并发发发发 肺炎肺炎n n已接受已接受长疗长疗长疗长疗 程程SCs,FQsSCs,FQs 治治疗疗疗疗n n已接受多种抗已接受多种抗GNBGNB治治疗疗疗疗不效不效n n所在社区流行所在社区流行MRSAMRSAn n吸毒者吸毒者n nMV7dMV7dn n气管插管患者下呼吸道分泌物涂片气管插管患者下呼吸道分泌物涂片见见见见GPCGPCDate14n近30余年来，MRSA不断增加，万古霉素成为治疗MRSA的代表性药物。虽然80出现另一种糖肽类药 物替考拉宁，但万古霉素似乎仍是治疗MRSA的主流品种。而且随着制剂进 一步纯化，从“Mississippi Mud”到很高纯度的白色粉末，消除了耳毒
14、性。除非与AMG联合使用，肾毒性很少出现。n万古霉素经历 的辉煌：抗MRSA的经典药物！Date15n随着MRSA 的增加，激起抗MRSA药物开发的高 潮，超过对 抗GNB药物的开发。部分药物已经上 市。n万古霉素的广泛应用，特别是治疗“艰难 梭杆菌肠 炎”（抗生素相关腹泻）口服万古霉素的过多使用 ，出现VRE并呈不断增加趋势 。n日本1996年发现 、1997年报道第一例万古霉素 中介耐药的MRSA以来，MRSA对万古霉素的耐药 成为世界热点和焦点。Date16CLSI关于万古霉素敏感性折点VRSAVISAVSSAMIC (g/ml)164-82hVISA （ MIC2g/ml ）heter
15、ogeneous Vancomycin- intermediate Staphylococcus Aureus不均质万古霉素中介金葡菌SA-RVS （ MIC4,8-16g/ml ）Staphylococcus Aureus with Reduced Susceptibility to Vancomycin 万古霉素敏感性减低金葡菌Date17VRSAVISAhVISAVSSAConcentration of vancomycin,g/mlFigure:Population analysis profile of vancomycin-resisitant Staphylococcus aur
16、eus(VRSA),vancomycin-intermediate S.aureus(VISA),heteroresistant VISA(hVISA),and vacomycin- susceptible S.aureus(VSSA)strains.Date18Shift in Vancomycin MICs1 Vancomycin MIC (mg/mL)YearS aureus Strains (n) 0.51200094579.9%19.9%2004141828.8%70.4%aa P32与治 疗失败存在相关，而不论MIC是否“敏感”n一组MRSA菌血症万古霉素100%敏感，但临床有效率 仅23%n有研究表明在低MIC菌株且体外以16g/ml万古霉素孵 育72h其体外杀菌显示增加的亚组临 床疗效提高n万古霉素疗效降低不仅与耐药基因有关，还与菌株合有 型辅助基因调节蛋白有关
