MRSA抗菌治疗进展PPT课件

MRSA的诊断及临床治疗2OUTLINEoMRSA的临床重要性oMRSA的药物敏感性及变迁oMRSA感染的抗菌治疗问题 1、 MRSA的临床重要性如何？o 耐药革兰阴性菌给临床带来的问题较革兰阳性菌更大，如鲍曼不动杆菌o 革兰阳性菌中， MRSA的临床重要性最大3.2 million bacterial isolates from 300 clinical lab 19982005 across the United StatesStyers D, et al. Ann Clin Microbiol Antimicrob 2006, 5:2.Staphylococcus aureusEscherichia coliEnterococcus spp.Coagulase-negative staphylococciPseudomonas aeruginosaKlebsiella pneumoniaeProteus mirabilisEnterobacter cloacaeSerratia marcescensAcinetobacter baumanniEscherichia coliStaphylococcus aureusEnterococcus spp.Pseudomonas 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 outpatients1.51.62.93.16.110.312.712.717.318.80 5 10 15 20 25 30 35 401.01.01.54.26.26.36.58.814.938.60 5 10 15 20 25 30 35 40S. aureus is a leading cause of bacterial infections in hospitals and community in the US中国革兰阳性菌菌种分布细菌 株数 金葡菌 6000 35.6 肠球菌属 4593 27.2凝固酶阴性葡萄球菌 3353 19.9（血液脑脊液等无菌体液）肺炎链球菌 1124 6.7-溶血性链球菌 1229 7.3草绿色链球菌（血液及无菌体液） 208 1.2其他 365 2.2合计 16872 100.0CHINET 2011金葡菌是临床最常见的革兰阳性菌MRSA可引起各类感染 骨髓炎食物中毒皮肤烫伤综合征T中毒休克综合征脓疱病疖肺炎眼内炎心内膜炎蜂窝织炎Annual Death Rates in the United StatesSelected Infectious DiseasesNo. of patients diedBoucher HW and Corey GR. Clin Infect Dis 2008;46:S344-9.MRSA感染的死亡病例数高于 AIDS的死亡病例数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. marcescensS. maltophiliaC. freundiiOthersKim JM. Am J Infect Control 2000;28:454-8. 91% of S. aureus were MRSA9MRSA 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conducted in 12 hospitals in China from 2008 to 2010 to know the incidence and causative pathogens of HAP.Liu YN, unpublished data by personal communicationPercentage(%)A. baumannii P. aeruginosaS. aureusK. pneumoniaeC. albicansS. maltophiliaE. coliE. cloacaeC. Tropical CoNSThe incidence of HAP varies from 0.9-4.1% in different hospitals in ChinaA. fumigatusDoern GV et al: Diagn Microbiol Infect Dis 1999;34:65Brook I: Int J Surg 2008;6:328Chira S, Miller LG: Epidemiol Infect 2010;138:313 Gram-positive organisms predominate (60-70% ) S. aureus - 48% in one study Group A -hemolytic streptococci - 26% Gram-negative organisms involved in 25-35% of infections Anaerobic and fungal organisms are uncommon Polymicrobial infections are encountered: Especially with deeper soft tissue infectionsMicrobiology in Skin/Soft Tissue Infections金葡菌是皮肤软组织感染的最常见病原菌11OUTLINEoMRSA的临床重要性oMRSA的药物敏感性及变迁oMRSA感染的抗菌治疗Prevalence of MRSA and MRCNS in Shanghai region since 1999问题 2、 MRSA对万古霉素的耐药性如何？是否存在 MIC漂移（ MIC creep）？MSSA(2954株 )与 MRSA(3033株 )的耐药率（ %）CHINET 2011耐药监测数据显示， MRSA对万古霉素、利奈唑胺 100敏感15Twelve VRSA (Vancomycin resistant S. aureus) reported in the USo Twelve cases from USAo Positive for the vanA geneo Median vancomycin MIC: 512 mg/Lo All patients had prior MRSA colonization or infectionso All had severe underlying factorsAAC 2009; 53: 4580-716Five VRSA reported in Asiao India: 3 strains n 2 strains: vancomyicn MIC 32 or 64 mg/L, vanA negativein addition, found 6 VISA strains (Tiwari HK, BMC Infect Dis 2006; 6: 156)n One VRSA vancomycin MIC64 mg/L, vanA positive (Saha B, et al. J Med Microbiol 2008; 57, 7279)o Iran: 2 strainsn One isolate had a vancomycin MIC of 64 mg/Ln Other one had a vancomycin MIC of 512 mg/L and vanA positive ( Aligholi M, et al. Med Princ Pract 2008; 17(5): 432)17异质性万古霉素中介金葡菌（ hVISA）在中国的发生情况o 1012株 MRSA于 2002-7年（主要为 05-07）分离自 14个城市o 检测方法：含药平皿及 MET初筛，菌群分析策略 -曲线下面积方法确认n hVISA 血培养 200 13.1 (26/199)VISA 1 (万古 MIC 4mg/L)非血培养 812 15.7（ 128/812）o 2007年分离自 14个城市 315株 MRSA， hVISA 9.5(30/315) (陈宏斌，中华检验医学杂志 2009; 32(11): 1223-7)Sun W, AAC 2009; 53(9): 3642-9How to detect VISA and hVISA ?19Clinical Infectious Diseases 2007; 44:153642 VISA 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 disc diffusion: for “S”E-Test: MIC2, but disc diffusion: for “S”MIC 8ug/ml “I”17mm zone “S”“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 method20MIC testing is recommended by CLSI to determine vancomycin susceptibility for MRSA since 2009* BHI+6g/ml vancomycin* send to reference lab21Comparison of laboratory detection methods of hVISAMethod Sensitivity SpecificityVancomycin broth MIC 11% 100%BHIA + BHIA6V 48 h, 4.512% 48 h, 68100%MHA + MHA5T 48 h, 6579% 48 h, 3595%MHA + MHA5T 48 h, 98% 48 h, 53%BHIA +Vancomycin 5g/ml， 10l of a 0.5 McFarlandstandard suspension 48 h, 120% 48 h, 5999%Simplified PAP* 48 h, 71% 48 h, 88%Macromethod Etest (MET) 48 h, 6998.5% 48 h, 8994%Etest GRD 24 h, 7077%48 h, 9394% 24 h, 98100%48 h, 8295%Benjamin 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 Vancomycin MIC creep：地区差异22Journal of Antimicrobial Chemotherapy (2007) 60, 78879423全球九国 10年（ 2001-2010）分离 MRSA万古霉素 MIC几何均数在 1mg/L左右 (0.661.13)Reynolds R, ECCMID 2012, P1215 Vancomycin Susceptibility in MRSA Over 10 Years: MIC Decrease After a Transient CreepVancomycin MIC mg/L: n (%)Year (n) 0.5-0.75 1.00 1.50 2.00 3.0-4.0 Means SD Vanco. use for MRSA02-03 (186) 0 6 (3.2) 86 (46.2) 85 (45.7) 9 (4.8) 1.78 0.39 95.0%05-06 (184) 1 (0.5) 2 (1.1) 95 (51.6) 70 (38.0) 16 (8.7) 1.82 0.47 91.0%08-09 (172) 0 0 110 (64.0) 61 (35.5) 1 (0.6) 1.69 0.26 93.2%10-12 (135) 2 (1.5) 15 (10.9) 97 (70.8) 20 (14.6) 1 (0.78) 1.52 0.30 93.5%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 targeted V trough levels were increased in early 2010 to 15-20 g/L 25OUTLINEoMRSA引起的常见感染oMRSA的药物敏感性及变迁oMRSA感染的抗菌治疗问题 3、目前临床应用的治疗 MRSA感染的抗菌药主要有哪些？各有什么优缺点？抗 MRSA的最主要抗菌药物27万古霉素Vancomycin利奈唑胺Linezolid达托霉素Daptomycin类型 糖肽类 噁 唑烷酮类