ICU常见的易发感染的疾病及其诊疗思路-M3

nullICU常见的易发感染的疾病及其 诊疗思路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是ICU永恒主题 ICU 工作要点之一是感染null75 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 expendituresnullSite of infectionDistribution of Nosocomial Infections by Site in Medical-Surgical ICU in USDistribution of Nosocomial Infections by Site in Medical-Surgical ICU in USInfect Control Hosp Epidemiol 2000;21:510-515. 83% of episodes of nosocomial pneumonia were associated with MV25%VAP27%VAPICU常见的易发感染的疾病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-ICUMohnarin 2011 ICU & Non-ICUnullnull18 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 admissionsFilamentous fungi: mainly invasive pulmonary aspergillosisnullSEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE. 2010. 31(1):79-86nullJournal of Intensive Care Medicine.2010,25(2):78-92nullClinical Infectious Diseases.2007,45:205-216Main pathogens in ICUMain pathogens in ICUE 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; AspergillosisESKAPE SEA ESKAPE2 球菌 + 2 真菌 + 3 肠杆菌科 + 3 非发酵菌 Bad bugs， No Drugs No ESKAPEMohnarin 2009-2011 ICU & Non-ICUMohnarin 2009-2011 ICU & Non-ICUMohnarin 2011 ICU & Non-ICU 铜绿假单胞菌体外药敏比较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 HAIThe pathogens of common HAIPneumonia (often ventilator-associated pneumonia, VAP) Catheter- associated urinary tract infection (UTI) Blood stream infection (BSI) Intra-abdominal infection (IAI)Causes of VAPCauses of VAPRespir Care.2005,50(6):742–763中国16家大型教学医院HAP临床调查(599例分离到694株菌)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致病原分离情况 早发性HAP vs 迟发性HAPThe pathogens of common HAIThe pathogens of common HAIPneumonia (often ventilator-associated pneumonia, VAP) Catheter- associated urinary tract infection (UTI) Blood stream infection (BSI) Intra-abdominal infection (IAI)nullKorean J Urol. 2013;54:59-65nullThe pathogens of common HAIThe pathogens of common HAIPneumonia (often ventilator-associated pneumonia, VAP) Catheter- associated urinary tract infection (UTI) Blood stream infection (BSI) Intra-abdominal infection (IAI)nullClinical Infectious Diseases 2004; 39:309–171995 - 2002Nosocomial bloodstream isolates ( SCOPE Study)nullClinical Infectious Diseases 2004; 39:309–17Nosocomial Bloodstream Isolates (SCOPE Study)9.8%23.2%67.0%nullThe pathogens of common HAIThe pathogens of common HAIPneumonia (often ventilator-associated pneumonia, VAP) Catheter- associated urinary tract infection (UTI) Blood stream infection (BSI) Intra-abdominal infection (IAI)Microbiology of Peritonitis 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 CandidaB. fragilis group Clostridium spp. E. coli Klebsiella spp. Streptococcus Enterococcus spp. CandidaE. coli Klebsiella spp. Streptococcus spp.Tertiary (Polymicrobial)2Secondary (Polymicrobial)1,2Primary (Monomicrobial)1null最初1-4周病原特征Microbiology of CA & HCA-IAI 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 StreptococcusHCA/HA-IAICA-IAIThe pathogens of common HAIThe pathogens of common HAIPneumonia (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(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 Sep–Dec; 2(3): 291–304耐药机制耐药机制酶：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膜孔蛋白 N Engl J Med. 2010;362:1804-13靶位改变 N Engl J Med. 2010;362:1804-13靶位改变 N Engl J Med. 2010;362:1804-13PBP外排泵 N Engl J Med. 2010;362:1804-13外排泵 N Engl J Med. 2010;362:1804-13nullAmpC-type β-lactamasesExtended-spectrum β-lactamases (ESBLs)CarbapenemasesPenicillinasesBroad-spectrum β-lactamases水解酶或钝化酶 b-lactamaseβ-Lactamases and antibioticsβ-Lactamases and antibioticsKorean j intern med. 2012, 27: 128-242A 类B 类D 类?nullβ-Lactamases and antibioticsICU常见感染抗生素选择策略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nullLocal ecologynullnullMake 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？nullN Engl J Med. 2010, 362;1804-13null碳青霉烯不敏感肠杆菌科 体外药敏实验Mariana C, et al. AAC. 2008: 570-573nullMake 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 nullMDR/XDR/PDR?CRPA? CRAB?nullMake your empirical antibiotics more appropriated -非发酵菌MDR/XDR/PDR? CRPA? CRAB?nullMake 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B\E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nullMake your empirical antibiotics more appropriated -非发酵菌-鲍曼不动杆菌 Current Opinion in Infectious Diseases 2010, 23:332–339nullN 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 / azithromycinnull2011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Make your empirical antibiotics more appropriated -非发酵菌-鲍曼不动杆菌nullExpanded off-label indications of newest antimicrobial agents for resistant GPCExpanded off-label indications of newest antimicrobial agents for resistant GPCnullnullMayo Clin Proc. 2011;86(8):805-817nullInvasive CandidiasisnullICU常见感染抗生素选择策略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 HAIAntimicrobial therapy for severe HAIGet it right the first time Hit hard upfront Broad-spectrum antibiotics (appropriate spectrum) Short period /duration De-escalation or stopped Pk-Pd individualizationIndications and best timing for starting antibiotic therapyIndications and best timing for starting antibiotic therapyEmergentUrgentDelayedAntimicrobial therapy for severe HAIAntimicrobial therapy for severe HAIGet it right the first time Hit hard upfront Broad-spectrum antibiotics (appropriate spectrum) Short period /duration De-escalation or stopped Pk-Pd individualizationMake your empirical antibiotics more appropriatedMake your empirical antibiotics more appropriatedHost characteristics The site of infection Knowledge of local ecology The severity of the diseasenullMDR?Severity?Cover G+? Antifungal?De-escalation?Fungal?Antimicrobial therapy for severe HAIAntimicrobial therapy for severe HAIGet it right the first time Hit hard upfront Broad-spectrum antibiotics (appropriate spectrum) Short period /duration （8d & 15d） De-escalation or stopped Pk-Pd individualizationnullPredetermined duration of antibiotic therapy by IDSA guidelinesAntimicrobial therapy for severe HAIAntimicrobial therapy for severe HAIGet it right the first time Hit hard upfront Broad-spectrum antibiotics (appropriate spectrum) Short period /duration De-escalation or stopped Pk-Pd individualizationAlgorithm for de-escalation decision-making at day3 in an improving patientAlgorithm for de-escalation decision-making at day3 in an improving patientCrit Care Clin. 2011, 27: 149 - 162nullCrit Care Clin. 2011, 27: 149 - 162Antimicrobial therapy for severe HAIAntimicrobial therapy for severe HAIGet it right the first time Hit hard upfront Broad-spectrum antibiotics (appropriate spectrum) Short period /duration De-escalation or stopped Pk-Pd individualizationInterrelationship among Pk-PdInterrelationship among Pk-PdVarghese JM, et al. Crit Care Clin. 2011, 27: 19-34Pk & Pd parameters of antibiotics on a C-T curvePk & Pd parameters of antibiotics on a C-T curveRoberts JA, et al. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med. 2009, 37:840-851.Pharmacodynamic propertiesPharmacodynamic propertiesRoberts JA, et al. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med. 2009, 37:840-851.T-D: Time-dependent; C-D: Concentration-dependentPk-Pd of newest antimicrobial agents for resistant GPCPk-Pd of newest antimicrobial agents for resistant GPCPk-Pd of newest antimicrobial agents for resistant GPCPk-Pd of newest antimicrobial agents for resistant GPC1. Bacteraemia, LRTI, skin and skin structure infection抗真菌药物的Pk-Pd抗真菌药物的Pk-PdMayo Clin Proc. 2011;86(8):805-817抗真菌药物的Pk-Pd抗真菌药物的Pk-PdM. sinnollareddy, et al. Int J Antimicrob Agents(2011), doi:10.1016nullPk-Pd of Antifungal Agentsnullβ-lactams; Carbapenemsβ-lactams; Carbapenems增加单次给药量、给药频率、延长输注时间（Extended/prolonged infusion）；持续输注（continuous infusion）能够使抗生素血清浓度更大限度保持于MIC值之上，更有利于发挥抗生素的抗菌活性，保证临床疗效。nullnullnullPk changes in critically ill patientsPk changes in critically ill patientsICU常见感染抗生素应用要点ICU常见感染抗生素应用要点Get it right the first time Hit hard upfront Broad-spectrum antibiotics (appropriate spectrum) Short period /duration De-escalation or stopped Pk-Pd individualization内容提要内容提要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