MRSA肺炎的诊治.ppt

1、,1,Shenzhen,南京军区南京总医院呼吸与危重症医学科2012.05.12杭州,MRSA肺炎的抗感染治疗,MRSA-全球性公共卫生问题,Hajo Grundmann, et al. Lancet 2006;368:874-85,美国：MRSA感染死亡人数超过AIDS,DeLeo and Chambers JCI 2009 adapted from Klevens et al. JAMA I2007,5,The Burden of MRSA,Increased hospitalization MRSA infections increase the median length of hos

2、pital stay for nosocomial infections (median: 12 days for MRSA versus 4 days for methicillin-susceptible S aureus MSSA) and surgical site infections (SSIs) (median: 23 days for MRSA versus 14 days for MSSA) Increased cost MRSA infections increase per-patient hospital costs in New York City hospitals

3、 by approximately $2500 to $3700 (expressed in 1995 dollars) compared with MSSA Direct hospital cost from nosocomial MRSA bacteremia is 2.8 times greater than that for MSSA bacteremia MRSA SSIs increase median hospital cost by approximately $40,000 compared with MSSA infections Increased mortality N

4、osocomial MRSA infections are associated with higher mortality compared with MSSA (21% versus 8%) MRSA SSIs are associated with a higher 90-day mortality rate (20.7% for MRSA versus 6.7% MSSA),Abramson MA, Sexton DJ. Infect Control Hosp Epidemiol. 1999;20:408-411. Engemann JJ et al. Clin Infect Dis.

5、 2003;36:592-598. Rubin RJ et al. Emerg Infect Dis. 1999;5:9-17.,ICU医院感染的主要致病原,EPIC II study：75个国家1265个ICU参加,JAMA. 2009;302(21):2323-2329,HAP致病原：SENTRY 2004-2008,N=31,436,Clinical Infectious Diseases 2010; 51(S1):S81S87,MRSA在欧洲的蔓延,Rates of hospital Staphylococcus aureus isolates that are methicillin

6、-resistant, based on samples from inpatient, outpatient, and ICU patients. Adapted from European Antimicrobial Resistance Surveillance System EARSS interactive database results (2),ANSORP： MRSA是亚洲地区HAP的主要致病菌,Asian HAP Working Group. Am J Infect Control 2008;36:S83-92.,2.胡必杰等.中华结核和呼吸杂志.2005;28(2):112

7、-116,院内肺炎分离菌株构成比(%),一项自2001.1-2003.12，对562例院内肺炎患者分离918株致病菌的监测结果显示,金黄色葡萄球菌占院内肺炎分离菌株第二位,n=171,n=148,n=148,n=132,n=81,中国16家大型教学医院呼吸科HAP致病原分离情况(599例分离到694株菌,2008-2010),其中87.8%为ORSA,MRSA是亚洲（及中国）HAP主要致病菌,Asian HAP Working Group. Am J Infect Control 2008;36:S83-92.,MRSA是导致院内肺炎患者死亡的危险因素之一,1997-2003年间，德国202家

8、ICU病房共8432例院内肺炎患者 多重对数回归分析患者死亡危险因素 耐药是导致死亡(更为严重疾病的替代指标)抑或不适当或延误治疗的因素么？ Gastmeier P, et al. ICHE 2007; 28: 466-72,Carmen Gonazalez et al. Clinical Infectious Diseases. 1999;29:1171-1177.,与MSSA组相比，MRSA组的死亡率增加31,MRSA感染死亡率明显高于MSSA,两个Meta分析比较了MRSA和MSSA菌血症的病死率,MRSA=methicillin-resistant Staphylococcus aur

9、eus; MSSA=methicillin-susceptible S. aureus; RR=relative risk. Cosgrove SE, Sakoulas G, Perencevich EN, et al. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis. 2003;36:53-59; Whitby M, McLaws

10、 ML, Berry G. Risk of death from methicillin-resistant Staphylococcus aureus bacteremia. Med J Aust. 2001;175:264-267.,延误正确的抗菌治疗导致病死率上升,Lodise TP et al, Clin Infect Dis 2003; 36:1418-1423. Iregui MI et al, Chest 2002; 122:262-268.,MRSA感染的分类,医疗卫生相关的MRSA感染（HA-MRSA感染） 社区发生的HA-MRSA感染（HCA-MRSA）： 在社区内发病，但

11、存在以下医源性感染的危险因素 发病时已带有侵入性的器械或装置 既往有MRSA感染或定植的历史 12个月内有手术、住院 、透析或居住在长期的卫生看护机构的历史 医院内发生的HA-MRSA感染 社区获得的MRSA感染（ CA-MRSA感染） 社区内发病，且不存在医源性感染的危险因素,JAMA, October 17, 2007；298(15)： 1763-71,Mortality after infection with (MRSA) diagnosed in the community,The cohort included 1439 patients diagnosed with MRSA a

12、nd 14,090 patients with no MRSA diagnosis. Within 1 year, 21.8% of MRSA patients died as compared with 5.0% of non-MRSA patients. The risk of death was increased in patients diagnosed with MRSA in the community (adjusted hazard ratio 4.1; 95% confidence interval: 3.54.7).,BMC Medicine 2008, 6:2,HA-M

13、RSA 与CA-MRSA的区别,Multidrug resistant (MDR), including: Clindamycin Gentamicin Fluoroquinolone SCCmec type 1-3 Usually PVL negative Associated with nosocomial pneumonia (NP) and skin, surgical site, and bloodstream infections Mortality:28%-56%,Can typically be treated with common oral antibiotics. Usu

14、ally only resistant to: Penicillin, oxacillin Erythromycin, fluoroquinolones SCCmec type 4 Usually PVL positive and other toxin and virulence factors may be present Associated with necrotizing skin, pulmonary, and bloodstream infections Mortality:42%-60%,HealthcareAssociated MRSA,CommunityAcquired M

15、RSA,PVL:Panton-Valentine Leukocidin , a virulence factor associated with skin/soft tissue infections as well as necrotizing pneumonia Naimi TS et al. JAMA. 2003;290:2976-2984. Deresinski S. Clin Infect Dis. 2005;40:562-573. Zetola N et al. Lancet Infect Dis. 2005;5:275-286.,HA-MRSA vs. CA-MRSA侵袭性感染的

16、主要类型,JAMA, October 17, 2007；298(15)： 1763-71,侵袭性感染：HA-MRSA vs. CA-MRSA高危人群的筛选和识别,有近期抗生素使用史的患者 氟喹诺酮类 头孢菌素类 住院时间2周的患者 入住ICU或烧伤病房 脑血管病后遗症昏迷患者 外科伤口感染或烧伤患者 I型糖尿病患者 长期腹膜透析/血液透析患者 接触MRSA感染或定植者的患者,日间看护中心的工作人员或被看护者 运动员及其密切接触者 军人或退伍军人 囚犯 无家可归者 男性同性恋患者 静脉注射毒品者 美洲原住民,HealthcareAssociated MRSA,CommunityAcquired

17、MRSA,流感样前驱症状； 严重的呼吸症状，如迅速进展的肺炎并发展为急性呼吸窘迫综合征（ARDS）； 高热，体温39； 咯血；低血压；白细胞减少； 胸片显示多叶浸润并可有空洞； 已知有CA-MRSA寄植或近期曾去流行区的历史（如北美旅行），近期与CA-MRSA感染或寄植者有接触； 属于CA-MRSA寄植率增加相关的人群； 以前有反复发生的疖或皮肤脓肿病史或家族史（在过去6个月内发生2次）,CA-MRSA引起CAP的线索,MRSA定植导致感染风险增加,Crit Care Med 2010 Vol. 38, No. 1，109,MRSA in Dialysis patients,5,287 cas

18、es of invasive MRSA cases reported by the Active Bacterial Core Surveillance in 2005 813 in dialysis patients with 45.2 cases per 1000 patients 70% of infections in those age 50 or greater 86% Bloodstream infections 17% mortality rate,多种危险因素同时存在进一步增加MRSA感染风险,INT: intubation; OW: open wound; TA: trea

19、tment with ATB; ST: steroid administration.,BMC Infectious Diseases 2011, 11:303,有助于早期识别MRSA感染的临床线索,皮肤软组织或骨关节的化脓性感染 菌血症样症状或局部脓肿形成 金葡菌感染的特殊临床表现 Scalded Skin Syndrome (SSS)、皮肤烫伤样改变 Rash、extremely Sensitive Toxic Shock Syndrome (TSS) Fever, rash, nausea 休克和心动过速 与胸部影像改变不相符的呼吸困难和紫绀 迅速出现的突破性感染,Clinical In

20、fectious Diseases 2010;51(S2):S183S197 Curr Opin Pulm Med 15:218222 International Journal of Antimicrobial Agents 30 (2007) 289296,Classical presentation of PVL-associated MRSA pneumonia, a previously fit young patient with an flu-like illness (pyrexia, myalgia, chills) diarrhea and vomiting toxic s

21、hock: Toxic shock: fever 39 C tachycardia 140 bpm hemoptysis hypotension marked leukopenia (may be normal early on) multilobar infiltrates on CXR, accompanied by effusions and often cavitation very high CRP level (often 200350 g/L) Sputum smear reveals sheets of staphylococci,International Journal o

22、f Antimicrobial Agents 30 (2007) 289296,考虑CA-MRSA肺炎的临床表现：（WHEN TO SUSPECT CA-MRSA PNEUMONIA）,Clin Pulm Med 2010;17: 260265,MRSA肺炎的影像特点,Primary MRSA pneumonia： necrotizing airspace disease multilobular, often bilateral involvement cavitating alveolar consolidation ”bubbly” consolidations NOT air-bron

23、chograms,CDR，2010；33：1-6,MRSA肺炎的影像特点,ground- glass opacities nodules Irregular,not round 可同时分布于内带及外带,CDR，2010；33：1-6,多发斑片影、结节影和“bubbly” consolidations,“,CDR，2010；33：1-6,MRSA肺炎的影像特点,Metastatic MRSA pneumonia multiple nodules with peripheral and basal predominance cavitating or noncavitating less roun

24、d likely to have a surrounding “ground-glass” halo,CDR，2010；33：1-6,MRSA肺炎的影像特点,Complications of MRSA pneumonia Abscess Empyema Bronchopleural fistula Acute respiratory distress syndrome（ARDS）.,CDR，2010；33：1-6,MRSA肺炎的确诊:最大问题是时间,肺炎的确诊：CAP or HAP? 致病原的确认：定植 or 感染？ 侵入性检查：BAL、PBS 定量培养 革兰染色涂片 致病原耐药性的确认 MS

25、SA or MRSA? MRSA来源的分析：HA-MRSA or CA-MRSA,我们目前对MRSA认识的现状,初始经验性治疗主要针对G-杆菌，极少覆盖MRSA。 原因： * 认识不足； * 在万古霉素时代认为只有分离到MRSA时才能用药； * 认为违反抗生素政策,基本认识,降阶梯治疗策略同样适用于G+球菌（MRSA）肺炎，即早覆盖。 一旦证明无MRSA时即停药。 短疗程不适用。,意大利udine教学医院：VAP经验性抗MRSA治疗,2项：加入抗MRSA经验性治疗,痰涂片革兰染色，报告？,培养阴性？,以下情况高度提示革兰阳性球菌感染 血流感染：包括导管相关的血流感染，菌血症，脓毒症，细菌性心内膜炎 皮肤软组织感染：包括伤口和创面感染 手术部位感染：包括植入物感染 骨和关节感染：骨髓炎,培养阴性？,以下情况有可能革兰阳性球菌感染 HAP（MRSA） VAP（MRSA） 复杂UTI（MRSA，肠球菌）,非呼吸机相关肺炎需要覆盖MRSA的 其他危险因素,流感、糖尿病、颅脑外伤、肾衰、昏迷并发肺炎 已接受长疗程SCs、FQs 治疗 已接受多种抗GNB治疗不效 所在社区