耐药背景下的个体化抗菌治疗.pptx

Click to edit Master title style,Click to edit Master text styles,Second Level,Third Level,Fourth Level,Fifth Level,陈 佰 义,中国医科大学从属第一医院感染病科,/,感染管理办公室,辽宁省医院感染管理质量控制中心,Chenbaiyi63,经验性抗感染治疗基本标准与临床实践,-,耐药背景下个体化抗感染治疗,耐药背景下的个体化抗菌治疗,第1页,Case study acute fever,既往健康,急性发烧、无器官系统感染临床表现,WBC,正常,阿奇霉素、红霉素、白霉素、洁霉素,.(,基层,),二代头孢、三代头孢、喹诺酮类、酶抑制剂复合制剂、厄他培南,.(,大医院,),耐药背景下的个体化抗菌治疗,第2页,The Mimics of,P,neumonia,感冒样症状,轻咳、少痰,渐进性气短,各种抗菌药品,-,广谱,+,联合,呼吸衰竭,耐药背景下的个体化抗菌治疗,第3页,慢性咳嗽和黄痰-原因,哮喘,后鼻腔鼻漏,病毒感染后气道高反应性,胃酸返流,吸烟相关慢性支气管炎,支气管扩张症,弥漫性泛细支气管炎肺泡蛋白沉积症,急性发烧,-WBC,不高,/,淋巴增高（无感染灶）,-,病毒！,-WBC,增高,/,中性粒增高,/,核左移,-,细菌,?,部位,/,病原体？,原发性菌血症？,慢性发烧,-IE,、布病、慢性感染灶？结核病？,-,非感染性发烧药品热、风湿病、恶性肿瘤,正确诊疗是正确治疗前提,发烧诊疗与判别诊疗,耐药背景下的个体化抗菌治疗,第4页,Mortality*Associated With Initial Inadequate Therapy in,Critically Ill ICU Patients,0%,20%,40%,60%,80%,100,%,Luna,1997,Ibrahim,Kollef,1998,Harbarth,Rello,1997,Alvarez-Lerma,1996,Initial adequate therapy,Initial inadequate therapy,*Mortality refers to crude or infection-related mortality.,Alvarez-Lerma F et al.,Intensive Care Med,1996;22:387-394.,Rello J et al.,Am J Respir Crit Care Med,1997;156:196-200.,Harbarth S et al.,Am J Med,;115:529-535.,Kollef MH et al.,Chest,1998;113:412-420.,Ibrahim EH at al.,Chest,;118:146-155.,Luna CM et al.,Chest,1997;111:676-685.,Valles J et al.,Chest,;123:1615-1624.,Mortality*,Valles,Inadequate Therapy Was Closely Associated With,Antibiotic Resistance,%Occurrence of Pathogen,Kollef MH.,Clin Infect Dis,;31(Suppl 4):S131-S138.,充分初始治疗改进预后,/,不充分治疗与耐药紧密相关,耐药背景下的个体化抗菌治疗,第5页,年在欧洲危重病会议和,ICC,从“猛击策略”到“降阶梯策略”,开始广覆盖,-,对于重症感染,开始即使用,广谱抗生素以覆盖全部可能致病菌,随即降阶梯,-48-72,小时后,依据微生物学检验结果调整抗生素使用,/,使之更有针对性,目标和意义,:,预防病情快速恶化,VS,预防细菌产生耐药,/,降低费用,“广覆盖”与“降阶梯”有机统一,对,VAP,最初治疗应针对,G-,和,G+,包含,MRSA,，,Gram,涂片发觉,G+,球菌与培养金葡萄阳性率之间高度一致。故涂片见,G+,菌应加用万古霉素,代表方案,-,泰能万古,耐药背景下的个体化抗菌治疗,第6页,48,岁、男性、同种异体肾移植术后,3.5,个月,13,天前出现发烧,（,T 38.9,），,继之咳嗽,/,无痰、进行性气短,胸片,先后,:,头孢呋辛,(3d),、莫西沙星,(3d),、哌拉西林,/,他唑巴坦,(3d),、亚胺培南,/,西司他丁万古霉素,(3d),查体,:,发绀、,RR 24/,分、,P 118/,分、双肺未闻及干湿罗音,ABG:PH 7.48,、,PO,2,56mmHg,、,PCO,2,30mmHg,Case study-PCP,耐药背景下的个体化抗菌治疗,第7页,58,岁、男性、既往身体健康,11,天前出现发烧,（,T 38.7,），,继之咳嗽，少痰；胸片,(,见右,),先后头孢唑林,(3d),、哌拉西林,/,他唑巴坦,(3d),，无效,病情继续加重，呼吸衰竭,ALT/AST/Bilirubins/LDH/CK-MB,Urinalysis-pro(+)WBC/RBC /CAST(+),再次胸片,(,见右,),换用碳青酶烯抗,MRSA,抗真菌,无效，呼吸衰竭，转诊,Case study-LD,耐药背景下的个体化抗菌治疗,第8页,58,岁、女性、自述既往身体“健康”,1,天前突然出现上消化道出血,诊疗,:,肝炎后肝硬化，食道静脉曲张出血,急诊行门脉断流手术,术后第二天出现发烧（,T 38.9,），继之咳嗽、咳痰，胸片,(,见右,),血气分析,:PaO2=56mmHg,（吸空气）,碳青酶烯,+,抗,MRSA+,抗真菌,临床转归,-,呼吸衰竭好转，下一步？,Case study-POP,耐药背景下的个体化抗菌治疗,第9页,问题在哪里？,经验性抗感染治疗基本标准与临床实践,耐药背景下的个体化抗菌治疗,第10页,Fighting Infection In The First hours,Rapid tests,When available.Gram stain!,Start adequate antibiotic coverage,(within 1 hour?),Tillou A et al.Am Surg;70:841-4,Drain purulent collection,Sampling,Including invasive procedures,when needed(BAL),经验性治疗和目标治疗统一,留取标本进行微生物学检验,开始经验性抗感染治疗,目标治疗,耐药背景下的个体化抗菌治疗,第11页,选择哪种抗菌药品,(which antibiotic?),感染部位常见病原学,(possible pathogens on site of infection),选择能够覆盖病原体抗感染药品,(antibiotics requirement),-,抗菌谱,/,组织穿透性,/,耐药性,/,安全性,/,费用,考虑药代动力学/药效动力学,(PK/PD),考虑病人生理和病理生理状态,(physiologic and pathophysiology),高龄/儿童/孕妇/哺乳,(advanced age/children/pregnant women/breast feeding),肾功效不全/肝功效不全/肝肾功效联合不全,(renal/heptic dysfunction/combined),其它原因,(other considerations),杀菌和抑菌/单药和联合/静脉和口服/疗程,(cidal vs static/mono vs combination/IV vs PO/duration),经验性抗感染治疗药品选择,-considerations in choosing antibiotic for empiric therapy,耐药背景下的个体化抗菌治疗,第12页,培养结果前依据基本信息选择抗感染药品,choosing Abx before culture result,感染部位和可能病原体关系,association of pathogen with site of infection,Gram,染色结果,-,与上述病原体是否符合？,Gram stain-in accordance with suspected pathogen?,一些病原体易于造成一些部位感染,Some pathogen easily cause some site of infection,经验性抗感染治疗药品选择,-considerations in choosing antibiotic for empiric therapy,不一样感染部位常见感染性病原体,Possible pathogens on site of infection,耐药背景下的个体化抗菌治疗,第13页,注意特殊修正因子,/,尤其是先期抗菌药品对细菌学影响,不一样感染部位常见感染性病原体,Possible pathogens on site of infection,耐药背景下的个体化抗菌治疗,第14页,关注特殊病原体,肺孢子菌肺炎,-,免疫缺点,-,相对特异临床,-,主动病原学检验,重症军团菌肺炎,发烧、少痰,多肺叶、多肺段受累,肺外表现,耐药背景下的个体化抗菌治疗,第15页,抗菌谱,(coverage),组织穿透性,(tissue penetration),耐药性,(resistance,specifically local resistance),参考代表性资料/依靠当地资料,安全性,(safety profile),药品本身/制剂/工艺/杂质,费用/效益,(cost/effectiveness),失败或副作用致再治疗费用更高,经验性抗感染治疗药品选,择基本标准,耐药背景下的个体化抗菌治疗,第16页,评价病原体耐药可能？,是否耐药菌？,-,了解耐药病原体流行情况,参考代表性治疗,/,依靠当地资料,-,个体化用药,病人起源：小区、养老院、医院,高龄、基础疾病、近期抗菌药品、近期住院、侵袭性操作、晚发医院感染,耐药背景下的个体化抗菌治疗,第17页,S.aureus,Penicillin,1944,Penicillin-resistant,S.aureus,金黄色葡萄球菌耐药发生发展过程,Methicillin,1962,Methicillin-resistant,S.aureus,(MRSA),Vancomycin-resistant,enterococci(VRE),Vancomycin,1990,s,1997,Vancomycin,intermediate,S.aureus,(VISA),Vancomycin-,resistant,S.aureus,CDC,MMWR,;51(26):565-567,1960,耐药背景下的个体化抗菌治疗,第18页,评价病原体耐药可能？,是否耐药菌？,-,了解耐药病原体流行情况,参考代表性治疗,/,依靠当地资料,-,个体化用药,病人起源：小区、养老院、医院,高龄、基础疾病、近期抗菌药品、近期住院、侵袭性操作、晚发医院感染,耐药背景下的个体化抗菌治疗,第19页,中国大陆,ESBL,发生率,%,Wang H,Chen M.Diagnos Microbiol Infect Dis,51,201-208CMSS/SEANIR/CARES.,year,细菌耐药监测结果怎样解读？,耐药背景下的个体化抗菌治疗,第20页,-:SMART-ESBL in community in China,E.coli,48h,21/59,36%,47/78,60%,48/82,59%,Klebsiella,48r,12/32,38%,12/33,36%,18/35,51%,Study done in referral tertiary university hospitals in China,Previous antibiotic exposure may select more ESLB-producer,SMART China might overestimate ESBL prevalence in China,耐药背景下的个体化抗菌治疗,第21页,试验室药品敏感性监测意义及缺点,意义,-,反应了耐药趋势,/,告诫我们要慎重使用抗菌药品,-,在制订用药方案时考虑耐药性造成治疗失败,缺点,-,试验室搜集到菌株,/,大型教学医院,/ICU,抗生素选择压力造成耐药性高估！,-,没有临床背景资料,/,不利用于个体化用药,(,年纪、基础疾病、小区,/,医院感染、前期抗菌药品使用,),耐药背景下的个体化抗菌治疗,第22页,Prevalence of rectal carriage of Extended-Spectrum-lactamase-producing Escherichia Coli among elderly people in a community setting in Shenyang,Cross sectional study-276 elderly,、,rectal swab/E coli isolation/ESBL screening,、,genotyping and PEGF,Result:,prevalence of ESBL positive E Coli 7.0%,（,19/270,）,CTX-M type,-CTX-M-14,63.2%,other:CTX-M-22 and CTX-M-24,，,2,CTX-M-57-like,-GA substitution in 865 point leading to DN subsitution in 289 point in AA(new,sequence No.EF426798),Tian SF,Chen BY.Prevalence of rectal carriage of Extended-Spectrum-lactamase-producing Escherichia Coli among elderly people in a community setting in Shenyang,China.,Canadian Journal of microbiology;54:15,耐药背景下的个体化抗菌治疗,第23页,评价病原体耐药可能？,是否耐药菌？,-,了解耐药病原体流行情况,参考代表性治疗,/,依靠当地资料,-,个体化用药,-,合理用药关键,病人起源：小区、养老院、医院,高龄、基础疾病、近期抗菌药品、近期住院、侵袭性操作、晚发医院感染,耐药背景下的个体化抗菌治疗,第24页,Risk factors for infection with ESBL producers(MDR),outside hospital,Factor,Odds ratio,R,x,3 gen ceph,15.8,R,x,2 gen ceph,10.1,Hospital in last 3 months,8.95,R,x,quinolone,4.1,R,x,penicillins,4.0,Antibiotic R,x,in last 3 months,3.23,Age 60 years,2.65,Diabetes,2.57,Colodner,et al EJCMID,23,163.,耐药背景下的个体化抗菌治疗,第25页,耐药背景下的个体化抗菌治疗,第26页,Univariate analysis of risk factors for carriage of ESBL-producing,Escherichia coli,in the community(n=270),Potential Risk factors No(%)ESBLs Total No Odds ratio(95%CI)P value,Age(years),74 16(7.4)216,75 3(5.6)54 0.74(0.21-2.62)0.77,Gender,Female 12(7.8)153,Male 7(6.0)117 0.81(0.31-2.13)0.81,Diabetes,No 11(6.3)174,Yes 8(8.3)96 1.35(0.52-3.47)0.62,Hospitalization in past one year,No 18(6.8)264,Yes 1(16.7)6 2.73(0.30-24.66)0.34,Surgery in past one year,No 19(7.1)268,Yes 0(0)2 0.0 0.8,Use of antibiotic in past three months,No 12(5.3)227,Yes 7(16.3)43 3.48(1.29-9.44).018,耐药背景下的个体化抗菌治疗,第27页,医院感染,-,产,ESBL,细菌感染危险原因,Prospective study of 455 episodes of K.pneumoniae bacteremia(253 nosocomial)in 12 hospitals,30.8%,为医院取得,ICU,中,43.5%,产,ESBLs,ESBLs,危险原因,-,先期使用氧亚氨基,-,内酰胺类抗菌药品,-,过去,14,天内使用,2 d(OR=3.9).,其它危险原因,TPN,肾功衰竭,烧伤,非,ESBL,危险,:,碳青霉烯、头孢吡肟、喹诺酮、氨基糖苷类,Paterson et al:Ann Intern Med;140:26-32.,耐药背景下的个体化抗菌治疗,第28页,VAP,耐药菌感染危险原因,135,次,VAP,ICU,变量,OR,P,MV7 days,6,.0,.009,先期,ABs,13,.5,7 days,/,prior ABs,Trouillet,et al.,Am J Respir Crit Care Med.,1998;157:531,耐药背景下的个体化抗菌治疗,第29页,No Risk Factors for MDR Pathogens,Risk Factors for MDR Enterobacteriaceae,a,Risk Factors for MDR,Pseudomonas,Health care contact,No,Yes!,(eg,recent hospital admission,nursing home,dialysis)without invasive procedure,Yes,Long hospitalization and/or infection following invasive procedures(5 days),Recent,Ab,x,No,Yes!,(14 days in past 90 days),Yes!,(14 days in past 90 days),Patient,characteristics,Young,few comorbidities,65 yrs,comorbidities such as,TPN or renal insufficiency,co,-,morbidities such as,CF,structural lung disease,advanced AIDS,neutropenia,or other severe immunodeficiency,a,Except nonfermenters/non-,Pseudomonas,species.,Adapted from Carmeli Y.Predictive factors for multidrug-resistant organisms.In:,Role of Ertapenem in the Era of Antimicrobial Resistance,newsletter.Available at:www.invanz.co.il/secure/downloads/IVZ_Carmeli_NL_W-226364-NL.pdf.Accessed 7 April;Dimopoulos G,Falagas ME.,Eur Infect,Dis,.;4951;Ben-Ami R,et al.,Clin Infect Dis,.;42(7):925934;Pop-Vicas AE,DAgata EMC.,Clin Infect Dis,.;40(12):17921798;Shah PM.,Clin Microbiol Infect,.;14(suppl 1):175180.,Stratification for Risk for MDR Gram-Negative Pathogens,耐药背景下的个体化抗菌治疗,第30页,Epidemiology of MRSA,H-MRSA,Reservoires,-hospitals,-LTCFs,5 genetic backgrouds,H-MRSA in community,-patients with risk factors,-contact with patients with,risk factors,True community-MRSA,-no healthcare-associated,risk factors,-with PVL genes,healthcare,community,Acquired,Onset,H-MRSA,感染危险原因,:,年纪,65,岁，严重基础疾病，伤口,广谱抗生素使用，住院时间延长，屡次住院,侵袭性操作（气管插管、切开,/,植入血管导管）,合理使用抗,MRSA,药品,糖肽类,/,利奈唑胺,耐药背景下的个体化抗菌治疗,第31页,重症感染耐药菌感染！,重症感染革兰阴性肠杆菌科细菌感染！,PCP,、军团菌、肺炎链球菌都可致重症感染,是否重症,?,-,依据临床表现,/,器官功效状态,-,氧和、血液动力学、肾功效 肠功效,PCP,LD,为何随意使用广谱抗菌药品和联合使,用？,耐药背景下的个体化抗菌治疗,第32页,Sepsis,SIRS plus Documented,Infection,重症感染临床判定,Severe Sepsis,Sepsis plus,organ failure,Septic shock,Severe sepsis and,Hypotension,Despite adequate ressucitation,SIRS-,at least 2 of the followings,T 38or 90 beats/min,RR 20 breaths/min,WBC 12,000 cells/ml,10%immature forms,ACCP/SCCM consensus conference 1992,耐药背景下的个体化抗菌治疗,第33页,重症感染临床判定,宿主原因,-Host factor,免疫缺点,高龄、疾病、治疗,感染所致临床综合征,中枢神经系统,-CNS,医院取得性肺炎,-HAP,呼吸机相关肺炎,-VAP,菌血症,-,Bacteremia,肺炎,-,pneumonia,原发性或不明原因,-,Primary or unknown,严重软组织感染,-,Severe soft tissue infection,病原体致病性,/,耐药性,High virulence or resistance,金黄色葡萄球菌,-S.aureus,铜绿假单孢菌,-P.aeruginosa,化脓性链球菌,-S.pyogenes,取得感染得场所,-Nosocomial infections,病人原因,-Patient factors,免疫缺点,-Immunocompromized,病情危重,-Critically ill,病原体原因,-Pathogen factors,高致病性和/或难治性微生物,Virulent and/or difficult to treat organisms,耐药背景下的个体化抗菌治疗,第34页,PCP,LD,耐药菌感染,VS,严重感染,-PCP,和,LD,告诉我们什么？,观点,:,耐药性判断,对于合理选择,抗菌药品更主要！,包含重症感染,耐药背景下的个体化抗菌治疗,第35页,选择哪种抗菌药品,(which antibiotic?),感染部位常见病原学,(possible pathogens on site of infection),选择能够覆盖病原体抗感染药品,(antibiotics requirement),-,抗菌谱,/,组织穿透性,/,耐药性,/,安全性,/,费用,考虑药代动力学/药效动力学,(PK/PD),考虑病人生理和病理生理状态,(physiologic and pathophysiology),高龄/儿童/孕妇/哺乳,(advanced age/children/pregnant women/breast feeding),肾功效不全/肝功效不全/肝肾功效联合不全,(renal/heptic dysfunction/combined),其它原因,(other considerations),杀菌和抑菌/单药和联合/静脉和口服/疗程,(cidal vs static/mono vs combination/IV vs PO/duration),经验性抗感染治疗合理选择药品,-considerations in choosing antibiotic for empiric therapy,评定病原体,有而放矢！,评定耐药性,到位不越位！,评定严重性,广谱,VS,窄谱？,单药,VS,联合？,耐药背景下的个体化抗菌治疗,第36页,选择哪种抗菌药品,(which antibiotic?),感染部位常见病原学,(possible pathogens on site of infection),选择能够覆盖病原体抗感染药品,(antibiotics requirement),-,抗菌谱,/,组织穿透性,/,耐药性,/,安全性,/,费用,考虑药代动力学/药效动力学,(PK/PD),考虑病人生理和病理生理状态,(physiologic and pathophysiology),高龄/儿童/孕妇/哺乳,(advanced age/children/pregnant women/breast feeding),肾功效不全/肝功效不全/肝肾功效联合不全,(renal/heptic dysfunction/combined),其它原因,(other considerations),杀菌和抑菌/单药和联合/静脉和口服/疗程,(cidal vs static/mono vs combination/IV vs PO/duration),经验性抗感染治疗药品选择,-considerations in choosing antibiotic for empiric therapy,耐药背景下的个体化抗菌治疗,第37页,联适用药理由,补充单一用药抗菌谱不足！,协同作用如铜绿假单孢菌菌血症,降低耐药？,耐药背景下的个体化抗菌治疗,第38页,ATS/IDSA Guidelines:Inpatients,Mandell LA,et al.,Clin Infect Dis,CAP Inpatient Therapy,Medical Ward,Intensive Care Unit,Recent,Antibiotic,No Recent,Antibiotic,Respiratory FQ,alone,OR,Advanced macrolide,+,-lactam,No,Pseudomonas,Risk,No-lactam Allergy,-lactam Allergy,-lactam,+,advanced,macrolide OR,+,respiratory FQ,*,Regimen depend on nature of recent Abx therapy,Respiratory FQ,+,aztreonam,Pseudomonas,Risk,No-lactam Allergy,-lactam Allergy,Anti-pseudomonal,antipneumococcal b-,lactam/penem,+,Cipro/Levo 750,OR,Anti-pseudomonal,antipneumococcal b-,lactam/penem,+,aminoglycoside,+,Azithromycin,Aztreonam,+,respiratory FQ,+,aminoglycoside,Advanced macrolide,+,-lactam,OR,respiratory FQ*,耐药背景下的个体化抗菌治疗,第39页,抗菌药品联合药敏,药品联合能够提升铜绿假单胞菌对药品敏感率,(,平均增加,3.4,9.2,),CID,，,40(Suppl 2),：,S89,一,S98,耐药背景下的个体化抗菌治疗,第40页,Novel Antibiotic Combinations against Infections with Almost Completely Resistant,Pseudomonas aeruginosa,and,Acinetobacter,Species,缺乏严格大规模、随机、对照临床研究,考虑联合治疗！,-,绿脓杆菌肺炎并菌血症,-IE,-,在高耐药地域，先联合，药敏结果明确后考虑停用一个药品,Rahal JJ.CID;43:S959,耐药背景下的个体化抗菌治疗,第41页,联合治疗曾被成功地用于抗结核治疗用于降低耐药性,在,HAP,和医院取得性血流感染中也缺乏结论性证据,间接证据证实联合治疗可能有用,丹麦学者对,1981,1995,14,年间,7938,次菌血症分离,8840,菌株进行了耐药性分析,结果肠杆菌科细菌对三代头孢菌素、碳青霉烯、氨基糖苷和氟喹诺酮类耐药性水平较低,(MIC,）,选择口服抗菌药品应该考虑,耐药背景下的个体化抗菌治疗,第44页,The Duration of Antimicrobial Therapy,Bacteria load,Clinical course,Recurrence,急性感染,Acute infection,慢性感染，疗程不足,Chronic infection,duration not enough,慢性感染，足疗程,Chronic infection,duration enough,耐药背景下的个体化抗菌治疗,第45页,选择哪种抗菌药品,(which antibiotic?),感染部位常见病原学,(possible pathogens on site of infection),选择能够覆盖病原体抗感染药品,(antibiotics requirement),-,抗菌谱,/,组织穿透性,/,耐药性,/,安全性,/,费用,考虑药代动力学/药效动力学,(PK/PD),考虑病人生理和病理生理状态,(physiologic and pathophysiology),高龄/儿童/孕妇/哺乳,(advanced age/children/pregnant women/breast feeding),肾功效不全/肝功效不全/肝肾功效联合不全,(renal/heptic dysfunction/combined),其它原因,(other considerations),杀菌和抑菌/单药和联合/静脉和口服/疗程,(cidal vs static/mono vs combination/IV vs PO/duration),经验性抗感染治疗药品选择,-considerations in choosing antibiotic for empiric therapy,评定病原体,/,评定耐药性,耐药背景下的个体化抗菌治疗,第46页,No simplistic policy,Homogenous protocol,Mixing,耐药背景下个体化治疗应该成为我们追求目标,耐药背景下的个体化抗菌治疗,第47页,THANK YOU,耐药背景下的个体化抗菌治疗,第48页,