(精品)严重感染治疗策略-邱海波2.ppt

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1、非发酵革兰阴性杆菌对三种碳青霉非发酵革兰阴性杆菌对三种碳青霉烯的敏感性烯的敏感性李家泰李家泰 中华检验医学杂志中华检验医学杂志,2005,28(1):25G-杆菌耐药对预后的影响lProspective cohort study.Dec 1996 to Sep 2000 Inpatient surgical wards at a university hospN=924 pats with GNR infectionslOutcomes were compared between GNR infections with and without antibiotic reslrGNRs:resi

2、stant to one or more of the followingall aminoglycosides,including amikacinall cephalosporinsall carbapenemsall fluoroquinolonesCrit Care Med 2003;31:10351041rGNR:入住ICUMVCRRT抗生素更换住院时间病死率小小 结结uESBL和和AmpC是是ICU重症感染致病菌耐药的重重症感染致病菌耐药的重要原因要原因u三代头胞大量使用是导致三代头胞大量使用是导致G-菌出现菌出现ESBL和和AmpC 的的 主要原因主要原因uESBL和和AmpC使

3、使ICU重症感染患者的病死率明重症感染患者的病死率明显增加显增加u近近3年年,ICU非发酵糖细菌的比例从非发酵糖细菌的比例从41.2%升高升高到到47.9%铜绿假单胞菌、不动杆菌属、嗜麦芽铜绿假单胞菌、不动杆菌属、嗜麦芽窄食单胞菌分别位居窄食单胞菌分别位居1、4、7位位u碳青霉烯类抗生素、酶抑制剂制剂等敏感性较碳青霉烯类抗生素、酶抑制剂制剂等敏感性较高高 ICU重症感染的重要性重症感染的重要性 细菌耐药机制及细菌耐药机制及ICUICU细菌流行情况细菌流行情况 重症感染的治疗策略重症感染的治疗策略 感染灶的充分引流感染灶的充分引流 早期经验性治疗与降阶梯策略早期经验性治疗与降阶梯策略 正确的目标

4、性治疗正确的目标性治疗内 容 提 要非抗生素治疗策略非抗生素治疗策略l气管插管与机械通气气管插管与机械通气n插管路径插管路径nNIV/IVn声门下的积液声门下的积液n气囊的管理气囊的管理n湿化与雾化湿化与雾化n管路与冷凝水管路与冷凝水nMV时间时间nICU的医疗强度的医疗强度l误吸误吸/体位体位n体位体位/胃肠道返流胃肠道返流n营养途径营养途径l口鼻咽腔口鼻咽腔/肠道定植肠道定植l溃疡预防溃疡预防/血糖控制血糖控制Source control-Grade EEvery pats presenting with severe sepsis should be evaluated for the

5、presence of a focus of infection amenable to source control measuresDrainage of an abscess or local focus of infectionRemoval of a potientially infected deviceGuidelines for sepsis.Intensive Care Med 2004,30:536-555 重症感染的重要性重症感染的重要性 细菌耐药机制及细菌耐药机制及ICUICU细菌流行情况细菌流行情况 重症感染的治疗策略重症感染的治疗策略感染灶的充分引流感染灶的充分引流

6、早期经验性治疗与降阶梯策略早期经验性治疗与降阶梯策略正确的目标性治疗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选择对常见致病菌有效的广谱抗生素k经验性治疗推理性治疗经验性治疗推理性治疗提高患者的生存率提高患者的生存率降低降低细菌产生耐药性细菌产生耐药性早期经验性治疗早期经验性治疗的的目标目标Dr.Jordi RelloProfessor of Critica

7、l Care,University Rovira&virgili Tarragona,Spain9早期及时抗生素治疗的重要性lIn a retrospective cohort study of pneumonia in 18,209 patientsAdministering antibiotics within 4 h of hospital arrival was associated with improved survival.Houck PM et al.Arch Intern Med.2004,164:637644Antibiotic therapy1.Grade EIntrav

8、enous 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 therapy2.Grade DbInitial empiric anti-infective therapy should include one or more drugs that have a

9、ctivity against the likely pathogensbThe 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 therapy早期经验性治疗早期经验性治疗是抗感染的经验性治疗方案，具有如下是抗感染的经验性治疗方案，具有如下两个特性：两个特性：开始开始即使用广谱抗生素以

10、覆盖所有可即使用广谱抗生素以覆盖所有可能的致病菌能的致病菌 随后随后(48-72h)(48-72h)根据微生物学检查结果根据微生物学检查结果调整抗生素的使用，使之更调整抗生素的使用，使之更有针对性有针对性Dr.Luciano GattinoniProfessor of Anesthesiology,Institute of Emergency Surgery,University of Milan,Italy如何保证起始治疗的准确性如何保证起始治疗的准确性Getting it right(A-protocol)lTreatment protocols and guidelines-import

11、ant tool for optimal therapyl Establishing local susceptibility profiles that can be used to develop therapy protocolsl“Not only we did want to treat with the initial therapy that was appropriate,but we wanted to minimize the emergence of resistance”CCM 2001CCM 2001，2929：1109110911151115如何保证起始治疗的准确性

12、如何保证起始治疗的准确性Getting it right(A)CCM 2001CCM 2001，2929：1109110911151115如何保证起始治疗的准确性如何保证起始治疗的准确性Getting it right(B-Bacteria resis)lIt is essential to be able to recognize those pats who are treatment failureCCM 2003CCM 2003，3131：676676抗生素治疗抗生素治疗抗生素治疗抗生素治疗3d3d3d3dVAPVAPVAPVAP无效无效无效无效-tended to be surviv

13、orstended to be survivorstended to be survivorstended to be survivors有效有效有效有效-tended to be non-S-tended to be non-S-tended to be non-S-tended to be non-SMore importantlyMore importantlyMore importantlyMore importantlyThose pats who had no Those pats who had no Those pats who had no Those pats who ha

14、d no clinical response within the clinical response within the clinical response within the clinical response within the first 3d were receiving first 3d were receiving first 3d were receiving first 3d were receiving inadequate antimicrobial inadequate antimicrobial inadequate antimicrobial inadequa

15、te antimicrobial therapytherapytherapytherapy 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 pneumoniaeOther:E coli,Haemophilus influ,Serrat

16、iaKollef 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的独立危险因素多重耐药致病菌多重耐药致病菌N=22MV 7天天抗生素：否抗生素：否N=12MV 36.5 and 38.5 and 39 or 4,000 and 11,000:0 11,000 1 Tracheal secretions Few0 Moderate1 Large2 PaO2/FiO2,mmHg 240 or present ARDS1 5 days)or risk factors forMDR PathogensNoYesLimited

17、 Spectrum TherapyBroad SpectrumTherapy for MDR PathogensAlgorithm for Initiating Empiric Antibiotic TherapyATS.Am J Respir Crit Care Med 2005;171:388-416Initial Empiric Antibiotic Therapyfor Patients with No Risk FactorsPotential PathogenStreptococcus pneumoniaeHaemophilus influenzaeMethicillin-sens

18、itive Staphylococcus aureusEnteric gram-negative bacilli(Antibiotic sensitive)Enterobacter species Escherichia coli Klebsiella species Proteus species Serratia marcescensRecommended AntibioticCeftriaxoneorLevofloxacin,moxifloxacin,or ciprofloxacinorAmpicillin/sulbactamorErtapenemATS.Am J Respir Crit

19、 Care Med 2005;171:388-416Potential PathogensP.aeruginosaESBL(+)K.pneumoniaeAcinetobacter speciesMRSAL.pneumophilaTherapyAntipseudomonal cephalosporin(cefepime,ceftazidime)orAntipseudomonal carbapenem(İmipenem,meropenem)orPiperacillin-tazobactamplusCiprofloxacin or levofloxacin orAminoglycosideLinez

20、olid or vancomycinInitial Empiric Antibiotic Therapyfor Patients with Risk Factors for MDR PathogensATS.Am J Respir Crit Care Med 2005;171:388-416 ICU重症感染的重要性重症感染的重要性 细菌耐药机制及细菌耐药机制及ICUICU细菌流行情况细菌流行情况 重症感染的治疗策略重症感染的治疗策略 感染灶的充分引流感染灶的充分引流 早期经验性治疗早期经验性治疗 正确的目标性治疗正确的目标性治疗内 容 提 要Antibiotic therapy3.Grade

21、EThe antimicrobial regimen should always be reassessed after 4872h 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l经验性治疗尽早转为目标性治疗经验性治疗尽早转为目标性治疗l转换所需时间反映

22、抗感染治疗水平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 l初始经验性治疗之前，应采集呼吸道标本初始经验性治疗之前，应采集呼吸道标本l呼吸道标本的病原学检查结果并不总是可靠的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细菌耐药性试验(药敏药敏)及时、正确、反复标本采样及时、正确、反复标本采样 标准化的细菌培养和药敏试验标准化的细菌培养和药敏试验选择敏感的抗生素选择敏感的抗生素监测：细菌培养和药敏监测：细菌培养和药敏如何实现目标性治疗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

23、学PharmacokineticsPharmacodynamicsDrug concentration at site of infectionSerum levelTissue levelEffectGrowth inhibitionKillingClinical cureClinical failure如何实现正确的目标性治疗如何实现正确的目标性治疗Getting it right(C-Decrease Res)36目标性治疗目标性治疗 组织渗透能力组织渗透能力l血浆浓度血浆浓度l组织浓度组织浓度37Therapeutic PrincipleTherapeutic PrincipleThe

24、 Need for Appropriate DosingThe Need for Appropriate DosingAntibioticDosage(in adult patients with normal renal and hepatic function)Antipseudomonal cephalosporin Cefepime CeftazidimeCarbapenems Imipenem Meropenem-lactam/-lactamase inhibitor Piperacillin/tazobactamAminoglycosides Gentamicin Tobramyc

25、in AmikacinAntipseudomonal quinolones Levofloxacin CiprofloxacinVancomycinLinezolid 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 hATS/IDSA.Am J Respir Cri

26、t Care Med 2005;171:388-416Initial Intravenous Adult Doses for Empiric Therapy of HAP,VAP,HCAPRelevant Clinical DefinitionslAppropriateThe etiologic organism is sensitive to the therapeutic agentlAdequateCorrect antibioticOptimal doseCorrect route of administration to ensure penetration at the site

27、of infectionUse of combination therapy if necessaryATS/IDSA.Am J Respir Crit Care Med 2005;171:388-416早期经验早期经验早期经验早期经验性治疗性治疗性治疗性治疗严重感染抗菌药物的原则严重感染抗菌药物的原则碳青霉烯类碳青霉烯类/酶抑制剂复合制酶抑制剂复合制剂、四代头孢剂、四代头孢或加或加或加或加Van(TeicoVan(Teico)或加抗真菌药物或加抗真菌药物或加抗真菌药物或加抗真菌药物 目标性目标性目标性目标性治疗治疗治疗治疗根据细菌学结果根据细菌学结果+临床疗效临床疗效,选用一选用一个广谱抗菌素或个广谱抗菌素或几个抗菌素联用几个抗菌素联用