严重感染治疗策略-邱海波2

null非发酵革兰阴性杆菌对三种碳青霉烯的敏感性非发酵革兰阴性杆菌对三种碳青霉烯的敏感性李家泰 中华检验医学杂志, 2005, 28(1): 25G-杆菌耐药对预后的影响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 fluoroquinolonesCrit Care Med 2003; 31:1035–1041rGNR: 入住ICU MV CRRT 抗生素更换 住院时间 病死率rGNR: 入住ICU MV CRRT 抗生素更换 住院时间 病死率小 结小 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 内 容 提 要 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 －正确的目标性治疗内 容 提 要null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Source control-Grade ESource control-Grade EEvery 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 deviceGuidelines for sepsis. Intensive Care Med 2004, 30: 536-555内 容 提 要 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 －正确的目标性治疗内 容 提 要早期经验性治疗的对象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早期有效抗感染治疗的重要性死亡： 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严重感染病人起始抗生素治疗覆盖面不足--死亡率增加 ICU严重感染病人起始抗生素治疗覆盖面不足--死亡率增加 ICU经验性抗生素治疗VAP: 22-73%为抗生素起始治疗不当null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 1997Adequate 38%(6/16) Not-adequate/not-ANT 81.6%(40/49) 132 pats with suspected NP BAL in 55 pats Bloodstream infectionsBloodstream infectionsLeibovici 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.Houck PM et al. Arch Intern Med. 2004, 164: 637–644Antibiotic therapyAntibiotic therapy1. Grade E Intravenous antibiotic therapy should be started within 1st h of recognition of severe sepsis, after appropriate cultures have been obtainedGuidelines for sepsis. Intensive Care Med 2004, 30: 536-555Antibiotic therapyAntibiotic therapy2. 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 hospitalGuidelines for sepsis. Intensive Care Med 2004, 30: 536-555Antibiotic therapynull早期经验性治疗是抗感染的经验性治疗 方案 气瓶 现场处置方案 .pdf气瓶 现场处置方案 .doc见习基地管理方案.doc关于群访事件的化解方案建筑工地扬尘治理专项方案下载 ，具有如下两个特性： 开始即使用广谱抗生素以覆盖所有可能的致病菌 随后(48-72h)根据微生物学检查结果调整抗生素的使用，使之更有针对性Dr. Luciano Gattinoni Professor of Anesthesiology,Institute of Emergency Surgery,University of Milan, Italy如何保证起始治疗的准确性 Getting it right (A--protocol)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” CCM 2001， 29：1109－1115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)CCM 2001， 29：1109－1115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” CCM 2001， 29：1109－1115如何保证起始治疗的准确性 Getting it right (B-Bacteria resis)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 failureCCM 2003， 31：676抗生素治疗3d－VAP 无效---tended to be survivors 有效---tended to be non-S More importantly Those pats who had no clinical response within the first 3d were receiving inadequate antimicrobial therapy Most common pathogens associated with inadequate initial antimicrobial threapy Most common pathogens associated with inadequate initial antimicrobial threapyPA: Pseuso aeruginosa; SA:Staphylococcus aureus; AS: Acinetobacter species; KP: Klebsiella pneumoniae; ES: Enterobacter species; SP: Strep pneumoniae Other: E coli, Haemophilus influ, SerratiaKollef MH Clinical Inf Dis 2000, 31 (S4):131-8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Trouillet JL et al.Am J Respir Crit Care Med 157:531-39, 1998HAP / VAP / HCAP合并MDR感染 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 therapyATS. Am J Respir Care Med 2005;171:388铜绿假单胞菌建议治疗方案－联合用药铜绿假单胞菌建议治疗方案－联合用药亚胺培南与阿米卡星联用，耐药率降至7％ 亚胺培南与环丙沙星联用，耐药率降至10％『1994～2001年中国重症监护病房非发酵糖细菌的耐药变迁』 中华医学杂志 2003，83，5；385－340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 useTrouillet JL. Am J Respir Crit Care Med 1998, 157: 531~539% susceptibility细菌耐药特点细菌耐药特点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天经验性治疗VAP的致病菌敏感性最高IMP＋Amikacin＋Vanco简化的临床诊断 标准 excel标准偏差excel标准偏差函数exl标准差函数国标检验抽样标准表免费下载红头文件格式标准下载 Clinical Pulmonary Infection Score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 2Luna CM. CCM, 2003, 31: 676 nullEmpiric Antibiotic Therapy for HAPHAP,VAP, or HCAP suspected (all disease severity)Late onset (>5 days) or risk factors for MDR PathogensNoYesLimited Spectrum TherapyBroad Spectrum Therapy for MDR PathogensAlgorithm for Initiating Empiric Antibiotic TherapyATS. Am J Respir Crit Care Med 2005;171:388-416Initial Empiric Antibiotic Therapy for Patients with No Risk FactorsInitial Empiric Antibiotic Therapy for Patients with No Risk FactorsPotential Pathogen Streptococcus pneumoniae Haemophilus influenzae Methicillin-sensitive Staphylococcus aureus Enteric gram-negative bacilli (Antibiotic sensitive) Enterobacter species Escherichia coli Klebsiella species Proteus species Serratia marcescensRecommended Antibiotic Ceftriaxone or Levofloxacin, moxifloxacin, or ciprofloxacin or Ampicillin/sulbactam or ErtapenemATS. Am J Respir Crit Care Med 2005;171:388-416Initial Empiric Antibiotic Therapy for Patients with Risk Factors for MDR PathogensPotential Pathogens P. aeruginosa ESBL (+) K. pneumoniae Acinetobacter species MRSA L. pneumophilaTherapy Antipseudomonal cephalosporin (cefepime, ceftazidime) or Antipseudomonal carbapenem (İmipenem, meropenem) or Piperacillin-tazobactam plus Ciprofloxacin or levofloxacin or Aminoglycoside Linezolid or vancomycin Initial Empiric Antibiotic Therapy for Patients with Risk Factors for MDR PathogensATS. Am J Respir Crit Care Med 2005;171:388-416内 容 提 要 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 －正确的目标性治疗内 容 提 要Antibiotic therapyAntibiotic therapy3. 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 costsGuidelines for sepsis. Intensive Care Med 2004, 30: 536-555Antibiotic therapy目标性治疗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 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)目标性治疗－药代动力学与药效学目标性治疗－药代动力学与药效学PharmacokineticsPharmacodynamicsDrug concentration at site of infection Serum level Tissue levelEffect 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)目标性治疗－ 组织渗透能力目标性治疗－ 组织渗透能力血浆浓度 组织浓度Therapeutic Principle The Need for Appropriate Dosing Therapeutic Principle The Need for Appropriate Dosing ATS/IDSA. Am J Respir Crit Care Med 2005;171:388-416Initial Intravenous Adult Doses for Empiric Therapy of HAP, VAP, HCAPRelevant Clinical DefinitionsRelevant Clinical DefinitionsAppropriate 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 necessarynull早期经验性治疗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null