ICU常见的易发感染的疾病及其诊疗思路.ppt

ICU常见的易发感染的疾病及其 诊疗思路,Jianguo Tang,Trauma-Emergency-Critical Care Medicine Center (T-E-CCMC),内容提要,ICU常见的易发感染的疾病 ICU获得性感染病原特征 ICU常见的易发感染病原学 ICU常见感染抗生素选择策略 ICU常见感染抗生素应用要点,内容提要,ICU常见的易发感染的疾病 ICU获得性感染病原特征 ICU常见的易发感染病原学 ICU常见感染抗生素选择策略 ICU常见感染抗生素应用要点,ICU 感染患者,感染性疾病诊治 感染的预防与控制,重症感染入住ICU ICU获得感染 （ICU-acquired infections）,ICU内获得性感染的预防与控制,感染相关问题是ICU永恒主题 ICU 工作要点之一是感染,75 countries 1265 ICUS 13 796 patients 7087 (51.4%) infected patients 9084 (71%) receiving antibiotics ICU mortality rate 25% (infected) & 11% (non-infected) (P .001) Infection accounted for 40% of total ICU expenditures,Site of infection,Distribution of Nosocomial Infections by Site in Medical-Surgical ICU in US,Infect Control Hosp Epidemiol 2000;21:510-515.,83% of episodes of nosocomial pneumonia were associated with MV,25%VAP,27%VAP,ICU常见的易发感染的疾病,Pneumonia (often ventilator-associated pneumonia, VAP) Catheter- associated urinary tract infection (UTI) Blood stream infection (BSI) Skin and wound infection Sinusitis Gastrointestinal infection (often with Clostridium difficile),内容提要,ICU常见的易发感染的疾病 ICU获得性感染病原特征 ICU常见的易发感染病原学 ICU常见感染抗生素选择策略 ICU常见感染抗生素应用要点,ICU感染的病原学,细菌 (G+; G-; 厌氧菌) 不典型细菌 真菌 病毒 etc,Mohnarin 2011 ICU & Non-ICU,18 ICUs 18-month study 105 episodes IFIs occurred in 5,561 Patients Candida: 16.5 cases/1,000 admissions Filamentous fungi: 2.3 cases/1,000 admissions,Filamentous fungi: mainly invasive pulmonary aspergillosis,SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE. 2010. 31(1):79-86,Journal of Intensive Care Medicine.2010,25(2):78-92,Clinical Infectious Diseases.2007,45:205-216,Main pathogens in ICU,E Enterococcus faecium E E.coli S Staphylococcus aureus K Klebsiella pneumoniae A Acinetobacter baumanii P Pseudomonas aeruginosa E Enterobacter species S Stenotrophomonas maltophilia A Candida albican; Aspergillosis,ESKAPE SEA ESKAPE,2 球菌 + 2 真菌 + 3 肠杆菌科 + 3 非发酵菌,Bad bugs， No Drugs No ESKAPE,Mohnarin 2009-2011 ICU & Non-ICU,Mohnarin 2011 ICU & Non-ICU 铜绿假单胞菌体外药敏比较,Mohnarin 2011 ICU & Non-ICU 鲍氏不动杆菌体外药敏比较,ICU获得性感染病原特征,G- 60-65%; G+ 35-40%; Fungal 15-25% SEA ESKAPE ICU: non-fermenting Antimicrobial-Resistance organisms in ICU,内容提要,ICU常见的易发感染的疾病 ICU获得性感染病原特征 ICU常见的易发感染病原学 ICU常见感染抗生素选择策略 ICU常见感染抗生素应用要点,The pathogens of common HAI,Pneumonia (often ventilator-associated pneumonia, VAP) Catheter- associated urinary tract infection (UTI) Blood stream infection (BSI) Intra-abdominal infection (IAI),Causes of VAP,Respir Care.2005,50(6):742763,中国16家大型教学医院HAP临床调查(599例分离到694株菌),不动杆菌属占所有病例数31.23%；占总GNB的38.56%,致病原分离情况 早发性HAP vs 迟发性HAP,The pathogens of common HAI,Pneumonia (often ventilator-associated pneumonia, VAP) Catheter- associated urinary tract infection (UTI) Blood stream infection (BSI) Intra-abdominal infection (IAI),Korean J Urol. 2013;54:59-65,The pathogens of common HAI,Pneumonia (often ventilator-associated pneumonia, VAP) Catheter- associated urinary tract infection (UTI) Blood stream infection (BSI) Intra-abdominal infection (IAI),Clinical Infectious Diseases 2004; 39:30917,1995 - 2002,Nosocomial bloodstream isolates ( SCOPE Study),Clinical Infectious Diseases 2004; 39:30917,Nosocomial Bloodstream Isolates (SCOPE Study),9.8%,23.2%,67.0%,The pathogens of common HAI,Pneumonia (often ventilator-associated pneumonia, VAP) Catheter- associated urinary tract infection (UTI) Blood stream infection (BSI) Intra-abdominal infection (IAI),Microbiology of Peritonitis,1. Laroche M, Harding G. Eur J Clin Microbiol Infect Dis. 1998;17:542-550. 2. Barie PS. J Chemother. 1999;11:464-477.,B. fragilis group Clostridium spp. Enterococci S. Epidermidis MRSA Pseudomonas+ A.baumannii Candida,B. fragilis group Clostridium spp. E. coli Klebsiella spp. Streptococcus Enterococcus spp. Candida,E. coli Klebsiella spp. Streptococcus spp.,Tertiary (Polymicrobial)2,Secondary (Polymicrobial)1,2,Primary (Monomicrobial)1,最初1-4周病原特征,Microbiology of CA & HCA-IAI,1. Laroche M, Harding G. Eur J Clin Microbiol Infect Dis. 1998;17:542-550. 2. Barie PS. J Chemother. 1999;11:464-477.,Enterobacter spp. Pseudomonas+ A.baumannii Enterococcus spp. MRSA Candida,E. coli Streptococcus,HCA/HA-IAI,CA-IAI,The pathogens of common HAI,Pneumonia (often ventilator-associated pneumonia, VAP) 非发酵菌、金葡菌、肠杆菌科 Catheter- associated urinary tract infection (UTI) ESBL+肠杆菌科、肠球菌、念珠菌 Blood stream infection (BSI) G+、G-、念珠菌 Intra-abdominal infection (IAI) 继发/第三类型/院内：非发酵/肠杆菌科、肠球菌、念珠菌,内容提要,ICU常见的易发感染的疾病 ICU获得性感染病原特征 ICU常见的易发感染病原学 ICU常见感染抗生素选择策略 ICU常见感染抗生素应用要点,ICU常见感染抗生素选择策略,细菌耐药与抗生素选择策略 不同耐药菌抗生素选择策略,MDR(多)-XDR(泛)-PDR(全),MDR is defined as non-susceptibility to at least one agent in 3 or more antimicrobial categories all penicillins and cephalosporins (including inhibitor combinations), fluroquinolones, and aminoglycosides XDR is defined as non-susceptibility to at least 1 agent in all but 2 or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories). PDR is defined as non-susceptibility to all agents in all antimicrobial categories (i.e. no agents tested as susceptible for that organism),J Glob Infect Dis. 2010 SepDec; 2(3): 291304,耐药机制,酶：水解酶或钝化酶或修饰酶 靶位改变(如核糖体和核蛋白)(Target alteration)：点发生突变使抗生素无法结合发挥作用 或被修饰使之与抗生素的结合不紧密 主动外排泵机制(Efflux pumps) 细菌细胞膜膜孔蛋白发生改变(Outer membrane porins: OMP) 细菌菌膜(Biofilm)的形成，使抗生素无法进入胞内的耐药机制,水解酶或钝化酶 N Engl J Med. 2010;362:1804-13,膜孔蛋白 N Engl J Med. 2010;362:1804-13,靶位改变 N Engl J Med. 2010;362:1804-13,PBP,外排泵 N Engl J Med. 2010;362:1804-13,AmpC-type -lactamases,Extended-spectrum -lactamases (ESBLs),Carbapenemases,Penicillinases,Broad-spectrum -lactamases,水解酶或钝化酶 b-lactamase,-Lactamases and antibiotics,Korean j intern med. 2012, 27: 128-242,A 类,B 类,D 类,?,-Lactamases and antibiotics,ICU常见感染抗生素选择策略,细菌耐药与抗生素选择策略 不同耐药菌抗生素选择策略,Local ecology,Make your empirical antibiotics more appropriated - 肠杆菌科,头霉素、磷霉素、阿米卡星、替加环素、多粘菌素？,N Engl J Med. 2010, 362;1804-13,碳青霉烯不敏感肠杆菌科 体外药敏实验,Mariana C, et al. AAC. 2008: 570-573,Make your empirical antibiotics more appropriated - PDR-肺克/大肠,多粘菌素 替加环素 亚胺培南/美洛培南 剂量 / 输注时间 磷霉素 利福平 氟喹诺酮 氨基糖苷 米诺环素、多西环素,联合用药,替加环素+多粘菌素 替加环素+磷霉素 替加环素+氨基糖苷类 碳青霉烯类+氨基糖苷类 碳青霉烯类+多粘菌素 碳青霉烯类+喹诺酮类,MDR/XDR/PDR?CRPA? CRAB?,Make your empirical antibiotics more appropriated -非发酵菌,MDR/XDR/PDR? CRPA? CRAB?,Make your empirical antibiotics more appropriated -非发酵菌-铜绿假单胞菌,抗假单胞菌青霉素类 哌拉西林/他唑巴坦、哌拉西林、替卡西林/克拉维酸 抗假单胞菌头孢菌素类 头孢哌酮/舒巴坦、头孢他啶、头孢吡肟、头孢哌酮、氨曲南 碳青霉烯类 美罗培南、亚胺培南 氨基糖苷类 阿米卡星、妥布霉素、庆大霉素 氟喹诺酮类 环丙沙星、左氧氟沙星 - 磷霉素 - 其他抗生素：多粘菌素BE,多为联合或上述药过敏而选用,厄他培南：对非发酵菌无效；替加环素：对铜绿无效,Make your empirical antibiotics more appropriated -非发酵菌-鲍曼不动杆菌,Current Opinion in Infectious Diseases 2010, 23:332339,N Engl J Med. 2010, 362;1804-13,CRAB: Colistin Sulbactam 6g/day Increase to 9g/day Tigecycline Meropenam 1-2g 3h q8h Imipenam .5-1g 3h q8h,+ rifampin / minocycline / doxycycline / azithromycin,2011年中国鲍曼不动杆菌感染诊治与防控专家共识,Make your empirical antibiotics more appropriated -非发酵菌-鲍曼不动杆菌,Make your empirical antibiotics more appropriated -非发酵菌-鲍曼不动杆菌,Expanded off-label indications of newest antimicrobial agents for resistant GPC,Mayo Clin Proc. 2011;86(8):805-817,Invasive Candidiasis,ICU常见感染抗生素选择策略,细菌耐药与抗生素选择策略 ESBL/AmpC/ Carbapenemases 不同耐药菌抗生素选择策略 肠杆菌科 非发酵菌：铜绿/鲍曼 G+ Fungal Candida/ aspergillosis,内容提要,ICU常见的易发感染的疾病 ICU获得性感染病原特征 ICU常见的易发感染病原学 ICU常见感染抗生素选择策略 ICU常见感染抗生素应用要点,Antimicrobial therapy for severe HAI,Get it right the first time Hit hard upfront Broad-spectrum antibiotics (appropriate spectrum) Short period /duration De-escalation or stopped Pk-Pd individualization,Indications and best timing for starting antibiotic therapy,Emergent,Urgent,Delayed,Antimicrobial therapy for severe HAI,Get it right the first time Hit hard upfront Broad-spectrum antibiotics (appropriate spectrum) Short period /duration De-escalation or stopped Pk-Pd individualization,Make your empirical antibiotics more appropriated,Host characteristics The site of infection Knowledge of local ecology The severity of the disease,MDR?,Severity?,Cover G+? Antifungal?,De-escalation?,Fungal?,Antimicrobial therapy for severe HAI,Get it right the first time Hit hard upfront Broad-spectrum antibiotics (appropriate spectrum) Short period /duration （8d & 15d） De-escalation or stopped Pk-Pd individualization,Predetermined duration of antibiotic therapy by IDSA guidelines,Antimicrobial therapy for severe HAI,Get it right the first time Hit hard upfront Broad-spectrum antibiotics (appropriate spectrum) Short period /duration De-escalation or stopped Pk-Pd individualization,Algorithm for de-escalation decision-making at day3 in an improving patient,Crit Care Clin. 2011, 27: 149 - 162,Crit Care Clin. 2011, 27: 149 - 162,Antimicrobial therapy for severe HAI,Get it right the first time Hit hard upfront Broad-spectrum antibiotics (appropriate spectrum) Short period /duration De-escalation or stopped Pk-Pd individualization,Interrelationship among Pk-Pd,Varghese JM, et al. Crit Care Clin. 2011, 27: 19-34,Pk & Pd parameters of antibiotics on a C-T curve,Roberts JA, et al. Pharmacokinetic issues for antibiotics in the critically ill patien