1、2023/1/7 1 MRSA感染的抗菌治疗 2023/1/7 2 McDonald LC.Clin Infect Dis.2022;42:S65-S71.Nosocomial infection Community-acquired infection Penicillinase-producing S aureus 0 25 50 75 100 1940 1960 1980 2000 Year Resistant isolates(%)Methicillin-resistant S aureus 0 25 50 75 100 1940 1960 1980 2000 Year Resista
2、nt isolates(%)Progression of resistant Staphylococcus aureus A similar trend in the increase in nosocomial infections caused by antimicrobial-resistant S aureus isolates can be observed in community-acquired infections 2023/1/7 3 Emergence of resistant pathogens Increase in nosocomial S aureus bacte
3、remia predominantly due to the increase in MRSA in the UK Wyllie D,et al.BMJ.2022;333:281-284.Cohort study in Oxfordshire,UK;MSSA=methicillin-sensitive Staphylococcus aureus a Per 100,000 admissions;b P.2.Year 400 500 300 200 150 100 50 1997 1999 2000 2001 2002 2003 2004 1998 Cases of S aureus Bacte
4、remiax Year 400 500 300 150 100 50 1997 1999 2000 2001 2002 2003 2004 1998 Cases of S aureus Bacteremiaa All Nosocomial S aureus Bacteremia b Year 400 500 300 200 150 100 50 1997 1999 2000 2001 2002 2003 2004 1998 Cases of S aureus Bacteremiax Year 400 500 300 200 150 100 50 1997 1999 2000 2001 2002
5、 2003 2004 1998 Cases of S aureus Bacteremiaa MSSA MRSA c b 2023/1/7 4 2023/1/7 5 HA-MRSA Strains High local prevalence History of MRSA infection or colonization Close contact with infected individual Extended hospitalization Resident of nursing home or long-term-care facility Invasive devices Dialy
6、sis Catheterization Enteral feeding Recent antibiotic use Risk factors for infection with MRSA CA-MRSA Strains High local prevalence History of MRSA infection or colonization Close contact with infected individual Crowded and/or unsanitary conditions Prison Military camp Depressed immune system Part
7、icipation in contact sports Sharing athletic equipment/towels Intravenous drug abuse 1.MRSA Infection.MayoClinic 2022.Availabe at:/mayoclinic /health/mrsa/DS00735/DSECTION=4.2.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
8、GJ,et al.N Engl J Med.2022;355:666-74.2023/1/7 6 2023/1/7 7 MRSA感染的危害感染的危害 MRSA感染可能 增加死亡风险1 增加患病率2,3 延长住院时间2,3 增加住院费用1,2,4 1.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 Resistance Task Force.Infect Control Hosp Epidem
9、iol.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.死亡率相关性比较死亡率相关性比较5：MRSA vs MSSA 比值比比值比 研究研究 MSSA:methicillin-sensitive staphylococcus aureus 2023/1/7 8 2023/1/7 9 2023/1/7 10 2023/1/7 11 2023/1/7 12 2023/1/7 13 VA
10、P致病菌与经验性抗生素治疗错误的致病菌与经验性抗生素治疗错误的比例比例 铜绿假单胞菌 MRSA 不动杆菌属 Kollef MH Clinical Inf Diseases 31 Suppl 4:131-8,Sept 2000 2023/1/7 14 肺炎肺炎(包括包括VAP)需要覆盖需要覆盖MRSA的考虑的考虑 流感、糖尿病、颅脑外伤、肾衰、昏迷并发流感、糖尿病、颅脑外伤、肾衰、昏迷并发肺炎肺炎 已接受长疗程已接受长疗程SCs,FQs 治疗治疗 已接受多种抗已接受多种抗GNB治疗不效治疗不效 所在社区流行所在社区流行MRSA 吸毒者吸毒者 MV7d 气管插管患者下呼吸道分泌物涂片见气管插管患者
11、下呼吸道分泌物涂片见GPC 2023/1/7 15 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，消除了耳毒性。除非与AMG联合使用，肾毒性很少出现。万古霉素经历的辉煌：抗MRSA的经典药物！2023/1/7 16 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。局部药物已经上市。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
12、加趋势。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。2023/1/7 17 CLSI关于万古霉素敏感性折点 VRSA VISA VSSA MIC(g/ml)16 4-8 2 hVISA （MIC2g/ml）heterogeneous 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
13、素敏感性减低金葡菌 2023/1/7 18 0123456781234567891011121314Log 10 cfu/mLVRSA VISA hVISA VSSA Concentration of vancomycin,g/ml Figure:Population analysis profile of vancomycin-resisitant Staphylococcus aureus(VRSA),vancomycin-intermediate S.aureus(VISA),heteroresistant VISA(hVISA),and vacomycin-susceptible S.
14、aureus(VSSA)strains.2023/1/7 19 Shift in Vancomycin MICs1 Vancomycin MIC(mg/mL)Year S aureus Strains(n)0.5 1 2000 945 79.9%19.9%2004 1418 28.8%70.4%a a P.01 compared to 2000.Implications of decreasing susceptibility to vancomycin Gradual reductions in vancomycin susceptibility in S aureus1,2 Vancomy
15、cin-intermediate S aureus(VISA)strains have emerged Treatment failure in MRSA bacteremia may occur within the susceptible vancomycin MIC range2 1.Wang G,et al.J Clin Microbiol.2022;44:3883-3886.2.Sakoulas G,et al.J Clin Microbiol.2004;42:2398-2402.Vancomycin MIC(g/mL)n Clinical Success 0.5 9 55.6%1.
16、0-2.0 21 9.5%CLSI MIC breakpoints:2 m mg/mL Susceptible 4-8 m mg/mL Intermediate 16 m mg/mL Resistant CLSI=Clinical and Laboratory Standards Institute.2023/1/7 20 SENTRY药敏监测19982003：金葡菌 年份 菌株数 MIC50 MIC90 根据MIC，分离株 2 g/mL 4 g/mL 8 g/mL 1998 5966 1 1 5.3 0 0 1999 5011 1 1 4.8 0 0 2000 6346 1 1 7.8 0.1 0.1 2001 5907 1 1 6.5 0.1 0 2002 7046 1 1 6.4 0 0 2003 5182 1 1 4.7 0 0 CID 2022；42S1：S13-S24 2023/1/7 21 Vancomycin MIC,0.5g/ml Zone diameter,17mm Vancomycin MIC,2g/ml Zone diameter,17mm Vancomycin
