菌感染淄博

ICU G-菌感染，为何特别关注？何为合理治疗？,山东大学齐鲁医院重症医学科 吴 大 玮,目录,G-菌感染发生率、病死率比g+菌更高为何 G-菌感染病死率比g+菌更高？G-菌耐药危险因素如何优化g-菌抗生素治疗治疗,细菌耐药已成为全球关注的焦点,2011年，世界卫生日主题为”抵御耐药性”2,在全球范围内，“ESKAPE”耐药已成为导致患者发病及死亡的重要原因1,“ESKAPE”耐药现象日益严重，但当前新型抗菌药物的研发逐渐减缓，未来可能面临无药可用的局面3,新药数量,1983-1987,1988-1992,1993-1997,1998-2002,2003-2007,1. Rice LB et al. The Journal of Infectious Diseases 2008; 197:1079812. /world-health-day/zh/3. Boucher HW et al. Clinical Infectious Diseases 2009; 48:112,我国耐药形式严峻,我国，“ESKAPE”耐药菌株检出率高,检出率(%),产ESBL大肠埃希菌,MRSA,产ESBL肺炎克雷伯菌属,不动杆菌属*,铜绿假单胞菌*,耐万古霉素屎肠球菌,*在G-菌中的检出率,朱德妹等.中国感染与化疗杂志.2011;11(5):321-329,为什么特别重视G-感染？,山东省ICU细菌耐药监测结果-解建,分离率高 耐药性强病死率高 耐药发展快,Marra AR,JCM, 2011, 49:1866,Marra AR,JCM, 2011, 49:1866,G-菌感染发生率更高,G-菌感染病死率更高-BSI,Marra AR,JCM, 2011, 49:1866,Nosocomial Bloodstream Infections in US Hospitals:Analysis of 24,179 Cases from a ProspectiveNationwide Surveillance Study,CID, 2004; 39:30917,Incidence rates and distribution of pathogens most commonly isolated from monomicrobial nosocomial bloodstream infections (BSIs) and associated crude mortality rates for all patients, patients in intensive care units (ICU), and patients in non-ICU wards.,Wisplinghoff H et al. Clin Infect Dis. 2004;39:309-317,G-菌感染病死率更高-BSI,G-菌感染病死率更高-VAP,48例PSB定量培养证实VAP，病死率 54.2%.其中绿脓和鲍曼VAP 病死率 71.4%。Fagon JY , The American journal of medicine 1993，94:281-8,The mortality of CAP: Respiratory sample with no definite/indeterminate EB/PA was 4.5,with EB as definite pathogens in respiratory samples was 20%, EB bacteraemia 22% and PA pneumonia 18% Eur Respir J 2010; 35: 598605,G-菌耐药性日趋严重-山东省ICU 2011,肺炎克雷白杆菌耐药率,不动杆菌杆菌耐药率,G-菌耐药性日趋严重-山东省ICU 2011,铜绿假单胞菌耐药率,大肠杆菌耐药率,目录,G-菌感染发生率、病死率比g+菌更高为何 G-菌感染病死率比g+菌更高？G-菌耐药危险因素如何优化g-菌抗生素治疗治疗,为何G- BSI病死率高？,CID, 2004; 39:30917,age, comorbidities, microbial aetiology, early and adequate initial antibiotic treatment.,与住院CAP患者病死率有关的因素,A. Torres，Eur Respir J 2010; 35: 473474,Date of download: 11/23/2012,Copyright 2012 American Medical Association. All rights reserved.,From: Community-Acquired Pneumonia Due to Gram-Negative Bacteria and Pseudomonas aeruginosa: Incidence, Risk, and Prognosis,Arch Intern Med. 2002;162(16):1849-1858. doi:10-1001/pubs.Arch Intern Med.-ISSN-0003-9926-162-16-ioi10503,Univariate and Multivariate Analyses of Individual Risk Factors for CAP Due to GNB*,Date of download: 11/23/2012,Copyright 2012 American Medical Association. All rights reserved.,From: Community-Acquired Pneumonia Due to Gram-Negative Bacteria and Pseudomonas aeruginosa: Incidence, Risk, and Prognosis,Arch Intern Med. 2002;162(16):1849-1858. doi:10-1001/pubs.Arch Intern Med.-ISSN-0003-9926-162-16-ioi10503,Incidence of causative gram-negative bacteria in community-acquired pneumonia according to the number of risk factors present. Independent risk factors identified in multivariate analyses (probable aspiration, previous hospital admission, previous antimicrobial treatment, and the presence of pulmonary comorbidity) were added as 0, 1, 2, and 3 or more. We used 2 analysis for linear trends to assess differences relative to baseline (no risk factor present; P14天入住ICU插管(包括胃造口术/经鼻胃管、尿路插管、中心静脉插管)机械通气,1.Kang CI et al. Ann Hematol. 2012 Jan;91(1):115-21. 2.Wu UI et al. J Microbiol Immunol Infect 2010;43(4):310316,产ESBL肠杆菌感染的高危因素,Bin Du,et al. Intensive Care Med .2002;28:17181723,既往使用头孢菌素是产生ESBL的主要危险因素,头孢菌素的选择性压力是肠科杆菌耐药的主要原因,头孢菌素的选择作用,主动外排机制：铜绿假单胞菌细胞外膜上有主动外排系统，该系统可将细菌体内的药物排出，致使药物浓度不足以发挥抗菌作用。渗透障碍： 细菌外膜有亲水性的外膜孔蛋白(Outer membrane protein，Omp)协助药物渗透入细菌体内，一旦Omp 缺失，则导致耐药产生。铜绿假单胞菌 Omp 的 OprO2 缺失是亚胺培南耐药的主 要 机 制 。 细 菌 生 物 被 膜 (Bacterial biologicalfacing，BBF)：铜绿假单胞菌是产生 BBF 的主要常见细菌。灭活酶与钝化酶：铜绿假单胞菌通过染色体或质粒介导可产生-内酰胺酶、氨基糖苷钝化酶及 DNA 旋转酶等，致相应抗菌药物耐药。第三代头孢菌素的不适当应用具有强烈诱导和筛选超广谱-内酰胺酶(ESBLs)的作用，导致第三代头孢菌素的耐药。,MDR-PA耐药机制：,MDR铜绿假单胞菌感染高危因素,MDR铜绿假单胞菌感染的单因素分析,Tumbarello M et al. Epidemiol. Infect. .2011;139:17401749.,一项回顾性病例对照研究，评估铜绿假单胞菌感染的高危因素及预后,粒细胞缺乏(粒细胞计数20天)插管(包括经鼻胃管、尿路插管、中心静脉插管)机械通气既往接受抗菌治疗、化疗和皮质激素治疗,Tumbarello M et al. Epidemiol. Infect. .2011;139:17401749.,MDR铜绿假单胞菌感染的高危因素,MDR鲍曼不动杆菌感染高危因素-1,研究显示，入住ICU，长期住院，鲍曼不动杆菌定植，近期接受抗菌治疗及治疗药物的数量，近期接受侵袭性操作是MDR鲍曼不动杆菌感染的高危因素,Anunnatsiri S et al. Southeast Asian J Trop Med Public Health. 2011 ;42(3):693-703.,一项前瞻性病例分析，评估MDR鲍曼不动杆菌所致菌血症的高危因素,Carbapenem Exposure:CR-AB,Emergence and Rapid Spread of Carbapenem Resistance during a Large and Sustained Hospital Outbreak of Multiresistant Acinetobacter baumannii.JOURNAL OF CLINICAL MICROBIOLOGY,Nov. 2000, p. 40864095,鲍曼不动杆菌耐药机制,Acinetobacter baumannii resistance mechanisms,目录,G-菌感染发生率、病死率比g+菌更高为何 G-菌感染病死率比g+菌更高？G-菌耐药危险因素如何优化g-菌抗生素治疗治疗,回本溯源: 诊疗感染性疾病的立足点：生物圈的轮回,1.Nicolau DP. Am J Manag Care.2000;6(suppl):S1202-S1210.2. Delacher S, Derendorf H, Hollenstein U, et al. J Antimicrob Chemother. 2000;46:733-739.,挽救生命,从三个角度关注和考虑临床抗生素的治疗方案,1.Nicolau DP. Am J Manag Care.2000;6(suppl):S1202-S1210.2. Delacher S, Derendorf H, Hollenstein U, et al. J Antimicrob Chemother. 2000;46:733-739.,细菌-患者：是否危及生命细菌-药物：是否存在MDR感染风险药物-患者：是否依循PK/PD的原理用药,MDR细菌感染增加医生的临床错误,增加低初始治疗抗生素选择的困难，降低初始治疗的恰当率，从而延迟患者获得恰当有效抗生素治疗的时机，可能需要的抗菌素毒性反应更大，杀菌效果更低。,Crit Care Med 2010; 38:S345S351,抗生素治疗不当1：抗菌谱未覆盖,Hospital mortality and infection related mortality rates for infected patients from all causes (n = 655) receiving either initially inadequate or adequate antimicrobial treatment.,Septic shock 相比出现低血压1小时给药，在2小时及以后给药的死亡率持续上升。,Kumar, Critical Care Medicine， 2006，34(6)； 1589-1596,1.67,92.6,odds ratio 1.119 (每小时延迟) ; 意味着每1小时延迟给药生存几率降低近12%,抗生素治疗不当2：给药延迟,Lodise TP J r, et al.Antimicrob Agents Chemother, 2007, 51: 3510-3515.,对于PA菌血症的治疗，若初始经验治疗不合适延迟52小时，将使病人30天死亡风险明显升高。,