非发酵革兰阴性杆菌对三种碳青霉烯的敏感性G- 杆菌耐药对预后的影响Prospective cohort study. Dec 1996 to Sep 2000 Inpatient surgical wards at a university hosp N=924 pats with GNR infections Outcomes were compared between GNR infections with and without antibiotic res rGNRs: resistant to one or more of the following all aminoglycosides, including amikacin all cephalosporins all carbapenems all fluoroquinolones rGNR: 入住ICUMVCRRT 抗生素更换 住院时间 病死率小结ESBL 和AmpC 是ICU 重症感染致病菌耐药的重要原因三代头胞大量使用是导致G- 菌出现ESBL 和AmpC 的主要原因ESBL 和AmpC 使ICU 重症感染患者的病死率明显增加近3年, ICU 非发酵糖细菌的比例从41.2% 升高到47.9% 铜绿假单胞菌、不动杆菌属、嗜麦芽窄食单胞菌分别位居1、4、7位碳青霉烯类抗生素、酶抑制剂制剂等敏感性较高ICU 重症感染的重要性细菌耐药机制及ICU 细菌流行情况重症感染的治疗策略－感染灶的充分引流－早期经验性治疗与降阶梯策略－正确的目标性治疗Source control-Grade E Every pats presenting with severe sepsis should be evaluated for the presence of a focus of infection amenable to source control measures Drainage of an abscess or local focus of infection Removal of a potientially infected device 重症感染的重要性细菌耐药机制及ICU 细菌流行情况重症感染的治疗策略－感染灶的充分引流－早期经验性治疗与降阶梯策略－正确的目标性治疗早期经验性治疗的对象对有急性而危及生命的全身性感染患者无法及时得到细菌学资料应根据本病房的细菌流行病学调查结果选择对常见致病菌有效的广谱抗生素经验性治疗＝推理性治疗ICU 严重感染病人起始抗生素治疗覆盖面不足-- 死亡率增加 Bloodstream infections Leibovici et al Adequate vs inadequate initial antibiotic: Mortality: 20% vs 34% 			From J Intern Med, 1998, 244: 379 早期及时抗生素治疗的重要性In a retrospective cohort study of pneumonia in 18,209 patients Administering antibiotics within 4 h of hospital arrival was associated with improved survival. Antibiotic therapy 1. Grade E Intravenous antibiotic therapy should be started within 1st h of recognition of severe sepsis, after appropriate cultures have been obtained Antibiotic therapy 2. Grade D Initial empiric anti-infective therapy should include one or more drugs that have activity against the likely pathogens The choice of drug should be guided by the susceptibility patterns of microorganisms in the community and the hospital 如何保证起始治疗的准确性Getting it right (A--protocol) Treatment protocols and guidelines---important tool for optimal therapy Establishing local susceptibility profiles that can be used to develop therapy protocols “Not only we did want to treat with the initial therapy that was appropriate, but we wanted to minimize the emergence of resistance”如何保证起始治疗的准确性Getting it right (A) 如何保证起始治疗的准确性Getting it right (A) “Not only we did want to treat with the initial therapy that was appropriate, but we wanted to minimize the emergence of resistance”如何保证起始治疗的准确性Getting it right (B-Bacteria resis) It is essential to be able to recognize those pats who are treatment failure Most common pathogens associated with inadequate initial antimicrobial threapy 机械通气时间与既往抗生素治疗是多重耐药致病菌VAP 的独立危险因素HAP / VAP / HCAP 合并MDR 感染危险因素Antimicrobial therapy in preceding 90 days Current hospitalization of 5 days or more High frequency of antibiotic resistance in the community or in the spesific hospital Presence of risk factors for HCAP Immunosuppressive disease and/or therapy 铜绿假单胞菌建议治疗方案－联合用药联合用药16 beds MICU of 1300 beds teaching hospital 1993.5~1995.6 VAP occurring after >7 d of MV and prior antibiotic use 细菌耐药特点VAP 病原菌耐药的危险因素: 最重要的是最近接受过抗生素治疗(最近15 天) 其次是机械通气至少7天简化的临床诊断标准Clinical Pulmonary Infection Score 		 Value			 Points Temperature C > 36.5 and < 38.4	0 		 > 38.5 and < 38.9 	1 		 > 39 or < 36			2 WBC,per mm-3 > 4,000 and < 11,000 :	0 		 < 4,000 or > 11,000 	1 	 Tracheal secretions Few			0 		 Moderate			1 		 Large			2 PaO2/FiO2, mmHg > 240 or present ARDS	1 		 < 240 and absent ARDS 	0 Pulmonary radiography no infiltrate 			0 		 	 Patchy or diffuse infiltrate 1 		 localized infiltrate 	2 Initial Empiric Antibiotic Therapyfor Patients with No Risk Factors Potential Pathogen Streptococcus pneumoniae Haemophilus influenzae Methicillin-sensitive Staphylococcus aureus Enteric gram-negative bacilli 	( Antibiotic sensitive ) Enterobacter species 	 Escherichia coli 	Klebsiella species 	 	Proteus species 	Serratia marcescens Recommended Antibiotic Ceftriaxone or Levofloxacin, moxifloxacin, or ciprofloxacin or Ampicillin/sulbactam or Ertapenem Potential Pathogens P. a eruginosa ESBL (+) K. pneumoniae Acinetobacter species MRSA L. pneumophila Therapy Antipseudomonal cephalosporin 	(cefepime, ceftazidime) or Antipseudomonal carbapenem 	( mipenem, meropenem) or Piperacillin-tazobactam	plus Ciprofloxacin or levofloxacin or Aminoglycoside Linezolid or v ancomycin ICU 重症感染的重要性细菌耐药机制及ICU 细菌流行情况重症感染的治疗策略－感染灶的充分引流－早期经验性治疗－正确的目标性治疗Antibiotic therapy 3. Grade E The antimicrobial regimen should always be reassessed after 48~72h on the basis of using a narrow-antibiotic to prevent the development of resistance, to reduce toxicity, and costs 目标性治疗经验性治疗尽早转为目标性治疗转换所需时间反映抗感染治疗水平病原学诊断的作用初始经验性治疗之前，应采集呼吸道标本呼吸道标本的病原学检查结果并不总是可靠的目标性治疗－药代动力学与药效学目标性治疗－组织渗透能力血浆浓度组织浓度Therapeutic PrincipleThe Need for Appropriate Dosing Relevant Clinical Definitions Appropriate The etiologic organism is sensitive to the therapeutic agent Adequate Correct antibiotic Optimal dose Correct route of administration to ensure penetration at the site of infection Use of combination therapy if necessary 早期经验性治疗Initial Empiric Antibiotic Therapyfor Patients with Risk Factors for MDR Pathogens ATS. Am J Respir Crit Care Med 2005;171:388-416 内容提要Guidelines for sepsis. Intensive Care Med 2004, 30: 536-555 Antibiotic therapy 细菌耐药性试验(药敏) 及时、正确、反复标本采样标准化的细菌培养和药敏试验选择敏感的抗生素监测：细菌培养和药敏如何实现目标性治疗Getting it right (A-Bac culture) Pharmacokinetics Pharmacodynamics Drug concentration at site of infection Serum level Tissue level Effect Growth inhibition Killing Clinical cure Clinical failure 如何实现正确的目标性治疗Getting it right (C-Decrease Res) 1-2 g every 8-12 h 2 g every 8 h 500 mg every 6 h 1 g every 8 h 4.5 g every 6 h 7 mg/kg per d 7 mg/kg per d 20 mg/kg per d 750 mg every d 400 mg every 8 h 15 mg/kg every 12 h 600 mg every 12 h Antipseudomonal cephalosporin Cefepime Ceftazidime Carbapenems Imipenem Meropenem -lactam/ -lactamase inhibitor Piperacillin/tazobactam Aminoglycosides Gentamicin Tobramycin Amikacin Antipseudomonal quinolones Levofloxacin Ciprofloxacin Vancomycin Linezolid Dosage (in adult patients with normal renal and hepatic function) Antibiotic ATS/IDSA. Am J Respir Crit Care Med 2005;171:388-416 Initial Intravenous Adult Doses for Empiric Therapy of HAP, VAP, HCAP ATS/IDSA. Am J Respir Crit Care Med 2005;171:388-416 严重感染抗菌药物的原则碳青霉烯类/酶抑制剂复合制剂、四代头孢或加Van(Teico) 或加抗真菌药物目标性治疗根据细菌学结果+ 临床疗效,选用一个广谱抗菌素或几个抗菌素联用* * 李家泰中华检验医学杂志, 2005, 28(1): 25 Crit Care Med 2003; 31:1035–1041 内容提要非抗生素治疗策略气管插管与机械通气插管路径NIV/IV 声门下的积液气囊的管理湿化与雾化管路与冷凝水MV 时间ICU 的医疗强度误吸/体位体位/胃肠道返流营养途径口鼻咽腔/肠道定植溃疡预防/血糖控制Guidelines for sepsis. Intensive Care Med 2004, 30: 536-555 内容提要提高患者的生存率降低细菌产生耐药性早期经验性治疗的目标Dr. Jordi Rello Professor of Critical Care ,University Rovira & virgili Tarragona, Spain 死亡：绝对危险度下降6.1% 早期有效抗感染治疗的重要性死亡：绝对危险度下降9％死亡：绝对危险度下降4% ICU 经验性抗生素治疗VAP: 22-73% 为抗生素起始治疗不当医院获得性肺炎-- 迅速恰当的抗生素治疗，明显提高生存率Luna CM et al.Chest 1997 Adequate		38%(6/16)	 Not-adequate/not-ANT	81.6%(40/49) 	 132 pats with suspected NP BAL in 55 pats Houck PM et al. Arch Intern Med. 2004, 164: 637–644 Guidelines for sepsis. Intensive Care Med 2004, 30: 536-555 Guidelines for sepsis. Intensive Care Med 2004