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1、严重感染严重感染的抗感染策略的抗感染策略 邱海波邱海波东南大学医学院附属中大医院东南大学医学院附属中大医院东南大学急诊与危重病医学研究所东南大学急诊与危重病医学研究所 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Sepsis = Infection+SIRS细菌侵入细菌侵入细菌侵入细菌侵入临床体征临床体征临床体征临床体征 infectioninfection损伤损伤损伤损伤 SIRS sepsis
2、SIRS sepsis severe sepsis severe sepsis septic shock MODS/ MOFseptic shock MODS/ MOF感染过程感染过程Impact of adequate empirical antibiotic therapy Impact of adequate empirical antibiotic therapy on the outcome of pats admitted to ICU with on the outcome of pats admitted to ICU with sepsissepsisCCM, 2019, 3
3、1: 2742CCM, 2019, 31: 2742lAnnual incidence of severe sepsis: 3 cases/ 1,000 lKill: 1,400 people worldwide /d 25 people /hlMoreover, No. of sepsis pats is projected to increase by 1.5% per annuml 严严重重感感染染的的病病死死人人数数超超过过乳乳腺腺癌癌、直直肠肠癌癌、结结肠癌、胰腺癌和前列腺癌的总和肠癌、胰腺癌和前列腺癌的总和l严重感染严重感染 vs AMI:发病率相同，病死率明显高发病率相同，病死率
4、明显高Sepsis in worldwide Surviving Sepsis Compaign拯救拯救Sepsis运动运动巴塞罗那宣言巴塞罗那宣言ESICM SCCM ISF 20192019年年1010月月2 2日日, , 西班牙西班牙l ll全全全全球球球球SepsisSepsis的的的的发发发发病病病病率率率率和和和和死死死死亡亡亡亡率率率率均均均均很很很很高高高高，耗耗耗耗费大量的人力物力费大量的人力物力费大量的人力物力费大量的人力物力l ll呼呼呼呼吁吁吁吁全全全全球球球球 医医医医务务务务专专专专业业业业人人人人员员员员和和和和组组组组织织织织、政政政政府府府府、卫生机构甚至公众
5、支持该行动卫生机构甚至公众支持该行动卫生机构甚至公众支持该行动卫生机构甚至公众支持该行动l llImprove survival in severe sepsisImprove survival in severe sepsisl llAIM: 5AIM: 5年内年内年内年内SepsisSepsis死亡率减少死亡率减少死亡率减少死亡率减少25%25%第一阶段第一阶段/Phase I/Phase Il llDevelop guidelines Develop guidelines Develop guidelines Develop guidelines l llBedside Bedside
6、Bedside Bedside clinician clinician clinician clinician could could could could use use use use to to to to improve improve improve improve outcome outcome outcome outcome in in in in severe severe severe severe sepsis sepsis sepsis sepsis ansansansans septic septic septic septic shock shock shock s
7、hock 第二阶段第二阶段/Phase II/Phase IIESICM SCCM ISFAACCN/ACCP/ACEP/ATS/ANZICS/ESCMID/ERS/SIFAACCN/ACCP/ACEP/ATS/ANZICS/ESCMID/ERS/SIFGuidelines for sepsis. Intensive Care Med 2019, 30: 536-555Guidelines for management of severe sepsis/ septic Guidelines for management of severe sepsis/ septic Guidelines f
8、or management of severe sepsis/ septic shockshockshockl llInitial resuscitation: early goal-directed therapyInitial resuscitation: early goal-directed therapyInitial resuscitation: early goal-directed therapyl llDiagnosis: appropriate cultureDiagnosis: appropriate cultureDiagnosis: appropriate cultu
9、rel llAntibiotic therapy: Early broad-spectrum, reassessed 2-3d Antibiotic therapy: Early broad-spectrum, reassessed 2-3d Antibiotic therapy: Early broad-spectrum, reassessed 2-3d l llSource controlSource controlSource control: : : l llFluid therapy: colloids=crystalloids,VLTFluid therapy: colloids=
10、crystalloids,VLTFluid therapy: colloids=crystalloids,VLTl llVasopressorsVasopressorsVasopressors: After VLS, NE : After VLS, NE : After VLS, NE vsvsvs DopaDopaDopa, Low-dose , Low-dose , Low-dose dopadopadopa is not , is not , is not , cathcathcath for for for vasovasovaso l llInotropicInotropicInot
11、ropic therapy: low CO- therapy: low CO- therapy: low CO-dobudobudobu, high CO is not, high CO is not, high CO is notl llSteroid: low dose Steroid: low dose Steroid: low dose l llrhAPCrhAPCrhAPC: APACHE II 25, sepsis-induced ARDS/MOF and : APACHE II 25, sepsis-induced ARDS/MOF and : APACHE II 25, sep
12、sis-induced ARDS/MOF and no bleeding riskno bleeding riskno bleeding risk第二阶段第二阶段/Phase II/Phase IIGuidelines for management of severe sepsis/septic Guidelines for management of severe sepsis/septic Guidelines for management of severe sepsis/septic shockshockshockl llBlood product administration: ta
13、rget Blood product administration: target Blood product administration: target HbHbHb 7-9g/dl, 7-9g/dl, 7-9g/dl, EPO only in renal failureEPO only in renal failureEPO only in renal failurel llMechanical ventilation: Mechanical ventilation: Mechanical ventilation: PplaPplaPpla30, 30, 30, HypercapniaH
14、ypercapniaHypercapnia, , , optimal PEEP, Prone positionoptimal PEEP, Prone positionoptimal PEEP, Prone positionl llSedation, analgesia and Sedation, analgesia and Sedation, analgesia and NBMsNBMsNBMs: Protocol: Protocol: Protocoll llGlucose control: 150mg%Glucose control: 150mg%Glucose control: 150m
15、g%l llRenal replacement: Renal replacement: Renal replacement: l llBicarbonate: pH 7.15Bicarbonate: pH 7.15Bicarbonate: pH 1616161616165 5 5 55 5头孢噻肟，阿米卡星头孢噻肟，阿米卡星头孢噻肟，阿米卡星头孢噻肟，阿米卡星头孢噻肟，阿米卡星头孢噻肟，阿米卡星头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟4444443232323232326 6 6 66 6头孢噻肟，庆大霉素头孢噻肟，庆大霉素头孢噻肟，庆大霉素头孢噻肟，庆大霉素头孢噻肟，庆大霉素头孢噻肟
16、，庆大霉素 头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟8 8 8 88 83232323232327 7 7 77 7头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟头孢噻肟444444323232323232161616161616头孢他啶，妥布霉素头孢他啶，妥布霉素头孢他啶，妥布霉素头孢他啶，妥布霉素头孢他啶，妥布霉素头孢他啶，妥布霉素 头孢他啶头孢他啶头孢他啶头孢他啶头孢他啶头孢他啶222222161616161616181818181818高产高产高产高产高产高产AmpCAmpCAmpCAmpCAmpCAmpC肠杆菌耐药与三代头孢使用的关系
17、肠杆菌耐药与三代头孢使用的关系肠杆菌耐药与三代头孢使用的关系肠杆菌耐药与三代头孢使用的关系肠杆菌耐药与三代头孢使用的关系肠杆菌耐药与三代头孢使用的关系vvv三代头孢使用三代头孢使用三代头孢使用三代头孢使用三代头孢使用三代头孢使用4-184-184-184-18天后就可选择出高产天后就可选择出高产天后就可选择出高产天后就可选择出高产天后就可选择出高产天后就可选择出高产AmpCAmpCAmpCAmpCAmpCAmpC霉肠杆菌耐药菌霉肠杆菌耐药菌霉肠杆菌耐药菌霉肠杆菌耐药菌霉肠杆菌耐药菌霉肠杆菌耐药菌Joseph W. Chow, MD, et al. Annals of Internal Medi
18、cine. 1991; 115:585-590Joseph W. Chow, MD, et al. Annals of Internal Medicine. 1991; 115:585-590AmpC酶流行情况酶流行情况约约30-50%肠杆菌属肠杆菌属 (弗劳地枸橼酸菌弗劳地枸橼酸菌,沙雷氏菌沙雷氏菌)高高产产AmpC酶酶131株三代头孢耐药的株三代头孢耐药的E coli的耐药分析的耐药分析 ESBLs 13.7% 高产高产AmpC34.0% 其他酶机制其他酶机制6.5%JAMA 2000产产AmpC酶耐药菌引发的临酶耐药菌引发的临床后果更加严重床后果更加严重l ll产产产产AmpCAmpC霉
19、肠杆菌属感染患者死亡率是霉肠杆菌属感染患者死亡率是霉肠杆菌属感染患者死亡率是霉肠杆菌属感染患者死亡率是非非非非耐耐耐耐药菌感染患者的药菌感染患者的药菌感染患者的药菌感染患者的2 2倍倍倍倍产产产产产产AmpCAmpCAmpC酶细菌感染的患者死亡率更高酶细菌感染的患者死亡率更高酶细菌感染的患者死亡率更高酶细菌感染的患者死亡率更高酶细菌感染的患者死亡率更高酶细菌感染的患者死亡率更高死亡率死亡率死亡率 % %15%15%15%32%32%32%P=0.03P=0.03P=0.03非耐药菌非耐药菌非耐药菌非耐药菌非耐药菌非耐药菌产产产产产产 AmpCAmpCAmpCAmpCAmpCAmpC 霉耐药菌霉
20、耐药菌霉耐药菌霉耐药菌霉耐药菌霉耐药菌Joseph W. Chow, MD, et al. Annals of Internal Medicine. 1991; 115:585-590ESBLs与高产与高产AmpC的差异的差异ESBLs 高产高产AmpC耐药谱耐药谱多重多重多重多重三代头孢三代头孢耐药耐药耐药耐药四代头孢四代头孢部分敏感部分敏感敏感敏感棒酸棒酸敏感敏感不敏感不敏感哌酮哌酮/舒巴坦舒巴坦多敏感多敏感耐药耐药 PIP/三唑三唑多敏感多敏感耐药耐药头霉素头霉素敏感敏感耐药耐药碳青霉烯类碳青霉烯类敏感敏感敏感敏感SSBL-24SSBL-24株阴沟肠杆菌的耐药情况株阴沟肠杆菌的耐药情况株
21、阴沟肠杆菌的耐药情况株阴沟肠杆菌的耐药情况酶型酶型株数株数 三嗪三嗪 他啶他啶 吡肟吡肟 亚胺配南亚胺配南AmpC+14 14 14 0 0ESBL+4 4 2 4 0AmpC+ESBL+5 5 5 20From PUMC hospital超级超级 内酰胺酶耐药内酰胺酶耐药(SSBL) Super Spectrum Beta LactamasesSuper Spectrum Beta LactamaseslESBLs/高产高产AmpC酶酶位于同一细菌或细菌质粒位于同一细菌或细菌质粒NPRS-7NPRS-7年最常见的革兰阴性菌（株数）年最常见的革兰阴性菌（株数）菌株数554 1048 1348
22、1542 1291 1678 1949总菌株总菌株1994199420192019年主要抗菌素对革兰阴性菌年主要抗菌素对革兰阴性菌敏感率变化趋势敏感率变化趋势敏感率MDRMulti-Drug-resistancelG-菌对四类抗生素中3/4类耐药Ceftazidine, Ciprofloxacin, Gentamicin, ImipenemPseudomonas aeruginosa, Acinetobacter speciesESBLs/AmpClG+MRSA非发酵糖细菌非发酵糖细菌1994-2019年，全国年，全国32家医院家医院ICU分离的分离的10279株株 G-菌中，菌中，分离分离4
23、450株非发酵糖细菌株非发酵糖细菌)铜绿假铜绿假单孢菌单孢菌46.9%46.9% 31%31%9.2%9.2%1.7%1.7%1.5%1.5%不动杆菌不动杆菌嗜麦芽窄嗜麦芽窄食单胞菌食单胞菌 产碱杆菌产碱杆菌黄杆菌属黄杆菌属洋葱伯克洋葱伯克霍尔德菌霍尔德菌1.7%1.7%1994199420192019年中国重症监护病房非发酵糖细菌的耐药变迁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中华医学杂志,2019,83(5):385-390,2019,83(5):385-390近近3年年, 非发酵糖细菌的比例从非发酵糖细菌的比例从41.2%升高到升高到47.9%铜绿假单胞菌、不动杆菌属、嗜麦
24、芽窄食单胞菌分别铜绿假单胞菌、不动杆菌属、嗜麦芽窄食单胞菌分别位居位居1、4、7位位铜绿假单孢菌的耐药性铜绿假单孢菌的耐药性(2019年年)22%22% 头孢哌酮头孢哌酮/舒巴坦舒巴坦哌拉西林哌拉西林/三唑巴坦三唑巴坦亚胺培南亚胺培南15%15%16%16%14%14%19%19%15%15%头孢他啶头孢他啶 头孢吡肟头孢吡肟阿米卡星阿米卡星1994199420192019年中国重症监护病房非发酵糖细菌的耐药变迁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中华医学杂志,2019,83(5):385-390,2019,83(5):385-390不动杆菌属的耐药性不动杆菌属的耐药性(201
25、9年年)46%46%3%3% 头孢哌酮头孢哌酮/舒巴坦舒巴坦哌拉西林哌拉西林/三唑巴坦三唑巴坦亚胺培南亚胺培南16%16%44%44%44%44%35%35%42%42%头孢他啶头孢他啶头孢吡肟头孢吡肟阿米卡星阿米卡星头孢噻肟头孢噻肟头孢曲松头孢曲松48%48%1994199420192019年中国重症监护病房非发酵糖细菌的耐药变迁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中华医学杂志,2019,83(5):385-390,2019,83(5):385-390R%7年嗜麦芽窄食单胞菌耐药率变迁年嗜麦芽窄食单胞菌耐药率变迁(%)1994199420192019年中国重症监护病房非发酵糖
26、细菌的耐药变迁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中华医学杂志,2019,83(5):385-390,2019,83(5):385-390 肠杆菌科细菌对三种碳青霉烯的敏感性肠杆菌科细菌对三种碳青霉烯的敏感性中国抗感染化疗杂志中国抗感染化疗杂志20192019年年3 3月月3030日第二卷第一期日第二卷第一期(3051) (357) (2118) (208) (1143) ( 22)uu 微生物学资料微生物学资料微生物学资料微生物学资料肠肝菌科细菌对三种碳青霉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, 2019, 28(1): 25 非发酵革兰阴性杆菌对三种碳青
27、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中国抗感染化疗杂志中国抗感染化疗杂志20192019年年3 3月月3030日第二卷第一期日第二卷第一期(1790) (169) (1365) (142 ) (323) uu 微生物学资料微生物学资料微生物学资料微生物学资料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, 2019, 28(1): 25G-杆菌耐药对预后的影响lProspective cohort study.Dec 2019 to Sep 2000 Inpatient surgical wards
28、 at a university hospN=924 pats with GNR infectionslOutcomes were compared between GNR infections with and without antibiotic reslrGNRs: resistant to one or more of the followingall aminoglycosides, including amikacinall cephalosporinsall carbapenemsall fluoroquinolonesCrit Care Med 2019; 31:1035104
29、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, 2019, 28(1): 25G-杆菌耐药对预后的影响lProspective cohort study.Dec 2019 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:
30、 resistant to one or more of the followingall aminoglycosides, including amikacinall cephalosporinsall carbapenemsall fluoroquinolonesCrit Care Med 2019; 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
31、和和AmpC使使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
32、策略 正确的目标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
33、for the 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 2019, 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
34、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的早期经验性治疗的目标目标Dr. Jordi RelloProfesso
35、r of Critical Care ,University Rovira & virgili Tarragona, Spain54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. 2019, 164: 637644Antibiotic t
36、herapy1. Grade EIntravenous antibiotic therapy should be started within 1st h of recognition of severe sepsis, after appropriate cultures have been obtainedGuidelines for sepsis. Intensive Care Med 2019, 30: 536-555Antibiotic therapy2. Grade DbInitial empiric anti-infective therapy should include on
37、e or more drugs that have activity 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 2019, 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
38、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)lTreatme
39、nt protocols and guidelines-important 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 2019CCM 20
40、19， 29 29：1109110911151115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 (A)CCM 2019CCM 2019， 29 29：1109110911151115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 2019CCM 2019， 31 31：676676抗生素治疗抗生素治疗抗生素治疗抗生素治疗3d3d
41、3d3dVAPVAPVAPVAP无效无效无效无效-tended to be survivorstended 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 ha
42、d no Those pats who had no Those pats who had 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 ant
43、imicrobial inadequate antimicrobial inadequate 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:
44、 Strep pneumoniaeOther: 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的独立危险因素多重耐药致病菌多重耐药致病菌N=22N=22MV7MV7天天抗生素：否抗生素：否N=12N=12MV7MV 36.5 and 38.5 and 39 or 4,000 and 11,000 :0 11,000 1 Tracheal secretions Few0 Moderate1 Large2 PaO2/FiO2, mmH
45、g 240 or present ARDS1 5 days) or risk factors forMDR PathogensNoYesLimited Spectrum TherapyBroad SpectrumTherapy for MDR PathogensAlgorithm for Initiating Empiric Antibiotic TherapyATS. Am J Respir Crit Care Med 2019;171:388-416Initial Empiric Antibiotic Therapyfor Patients with No Risk FactorsPote
46、ntial PathogenStreptococcus pneumoniaeHaemophilus influenzaeMethicillin-sensitive Staphylococcus aureusEnteric gram-negative bacilli(Antibiotic sensitive) Enterobacter species Escherichia coli Klebsiella species Proteus species Serratia marcescensRecommended AntibioticCeftriaxoneorLevofloxacin, moxi
47、floxacin, or ciprofloxacinorAmpicillin/sulbactamorErtapenemATS. Am J Respir Crit Care Med 2019;171:388-416Potential PathogensP. aeruginosaESBL (+) K. pneumoniaeAcinetobacter speciesMRSAL. pneumophilaTherapyAntipseudomonal cephalosporin(cefepime, ceftazidime) orAntipseudomonal carbapenem(İmipenem, me
48、ropenem) orPiperacillin-tazobactamplusCiprofloxacin or levofloxacin orAminoglycosideLinezolid or vancomycinInitial Empiric Antibiotic Therapyfor Patients with Risk Factors for MDR PathogensATS. Am J Respir Crit Care Med 2019;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
49、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 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. Intens
50、ive Care Med 2019, 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
51、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-D
52、ecrease Res)80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81Therapeutic PrincipleTherapeutic PrincipleThe Need for Appropriate DosingThe Need for Appropriate DosingAntibioticAntibioticDosageDosage(inadultpatientswithnormalrenal(inadultpatientswithnormalrenalandhepaticfunction)andhepaticfunction)Antipse
53、udomonalcephalosporinAntipseudomonalcephalosporinCefepimeCefepimeCeftazidimeCeftazidimeCarbapenemsCarbapenemsImipenemImipenemMeropenemMeropenem-lactam/-lactam/-lactamaseinhibitor-lactamaseinhibitorPiperacillin/tazobactamPiperacillin/tazobactamAminoglycosidesAminoglycosidesGentamicinGentamicinTobramy
54、cinTobramycinAmikacinAmikacinAntipseudomonalquinolonesAntipseudomonalquinolonesLevofloxacinLevofloxacinCiprofloxacinCiprofloxacinVancomycinVancomycinLinezolidLinezolid1-2gevery8-12h1-2gevery8-12h2gevery8h2gevery8h500mgevery6h500mgevery6h1gevery8h1gevery8h4.5gevery6h4.5gevery6h7mg/kgperd7mg/kgperd7mg
55、/kgperd7mg/kgperd20mg/kgperd20mg/kgperd750mgeveryd750mgeveryd400mgevery8h400mgevery8h15mg/kgevery12h15mg/kgevery12h600mgevery12h600mgevery12hATS/IDSA. Am J Respir Crit Care Med 2019;171:388-416Initial Intravenous Adult Doses for Empiric Therapy of HAP, VAP, HCAPRelevant Clinical DefinitionslAppropri
56、ateThe etiologic organism is sensitive to the therapeutic agentlAdequateCorrect antibioticOptimal doseCorrect route of administration to ensure penetration at the site of infectionUse of combination therapy if necessaryATS/IDSA. Am J Respir Crit Care Med 2019;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(Teico)Van(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
