细菌耐药的临床对策-关注抗菌药物临床管理及合理应用

陈 佰 义中国医科大学附属第一医院感染病科/感染管理科辽宁省医院感染管理质控中心 C,细菌耐药的临床对策 -关注抗菌药物临床管理及合理应用,抗感染药物发展简史,1929 Alexander Fleming 发现青霉素,Howard Florey 和 Ernst Chain分离获得青霉素，用于动物试验。,青霉素首次用于救治战伤患者，拯救了 许多人的生命,1950s 大量抗生素用于临床。,A poster from World War II, dramatically showing the virtues of the new miracle drug, and representing the high level of motivation in the country to aid the health of the soldiers at war.,Discovery of Antibacterial Agents,CycloserineErythromycinEthionamideIsoniazidMetronidazolePyrazinamideRifamycinTrimethoprimVancomycinVirginiamycin,Imipenem,1930,1940,1950,1960,1970,1980,1990,2000,PenicillinProntosil,Cephalosporin C,EthambutolFusidic acidMupirocinNalidixic acid,OxazolidinonesCecropin,Fluoroquinolones,Newer aminoglycosides,Semi-synthetic penicillins & cephalosporins,Newer carbapenems,Trinems,Synthetic approaches,Empiric screening,Newer macrolides & ketolides,Rifampicin,Rifapentine,Semi-synthetic glycopeptidesSemi-synthetic streptogramins,NeomycinPolymixinStreptomycinThiacetazone,Chlortetracycline,Glycylcyclines,Minocycline,Chloramphenicol,“Close the book on infectious disease”,“Infectious disease will be with us for the foreseeable future”,US Surgeon General William Stewart, 1969,Harvard Medical School Mary Wilson, 1998,抗生素时代感染仍是人类健康的主要威胁之一,IIIIIIII,新出现或“再出现”的感染性疾病 emerging and re-emerging infectious diseases,新病原体不断出现-HIV/AIDS、Ebola、Hantavirus 新型肝炎、新型克雅病（疯牛病）肠杆菌O157、霍乱O139 环孢子菌病、隐孢子菌病、人类Ehrlichosis老病卷土重来-肺结核、疟疾、鼠疫、霍乱、黄热病、登革热 和登革出血热免疫缺陷人群不断增加-机会性真菌和呼吸道病毒性肺炎细菌耐药愈演愈烈PRSP、MRSP、MRSA/MRSE、VRE、VISA/VERA ESBL、ampC、SSBL、金属酶. MDR结核菌 美国因细菌耐药增加医疗费用超过40亿美元!,临床关注的耐药问题Resistances of Clinical Concerns,革兰阳性细菌金匍菌 MRSA, VISA, VRSAVRE (地理上差别)肺炎链球菌 青霉素和喹诺酮耐药 革兰阴性细菌肠杆菌科ESBLs喹诺酮,头孢菌素,青霉素类,氨基糖苷类碳青霉烯类非发酵菌(假单孢菌+/-不动杆菌)喹诺酮, 头孢菌素,青霉素类,氨基糖苷类,碳青霉烯类,Antibiotic resistance: genetic events,Susceptible bacteria,Selection for Antimicrobial-Resistant Strains,抗生素选择压力,耐药菌的播散,Antibiotic Control and Infection Control:The Two Sides of the Resistance “Coin”,Rekha Murthy. Implementation of Strategies to Control Antimicrobial Resistance Chest 2001;119;405-411,Control of Antibiotic Resistance,寻找新的抗感染药物 -新药越来越少限制人以外(畜牧业)使用 -减少对人类的影响加强抗感染药物的临床管理 -分级和分线优化抗感染药物预防 VS 治疗 优化抗感染药物临床管理 加强医院感染的控制 -减少耐药菌传播,细菌耐药的临床对策 -Measures to Resistance,-减少抗生素选择性压力,抗感染药物的临床应用,治疗性应用经验治疗 因无法确定感染的微生物，推断可能的病原体，参考本地 区药敏监测结果，故抗生素必须覆盖所有可能的微生物， 常选用联合治疗或单一广谱抗生素,治疗性应用目标治疗 确定病原体，选用窄谱、低毒性的抗生素,预防性应用,Fighting Infection In The First hours,Rapid testsWhen available. Gram stain!,Start adequate antibiotic coverage(within 1 hour?)Tillou A et al. Am Surg 2004;70:841-4,Drain purulent collection,SamplingIncluding invasive procedureswhen needed (BAL),经验性治疗和目标治疗的统一留取标本进行微生物学检查开始经验性抗感染治疗目标治疗,Factors Selected by Multivariate Analysis Independently Related to Mortality,Leroy O Intensive Care Med 1995; 21:24-31,Importance of Adequate and Appropriate Antimicrobial Treatment,Adequate antimicrobial treatment,Mortality,Increased,Decreased,Inadequate antimicrobial treatment,Ongoing bacterial proliferation and inflammationselection of drug-resistant microorganisms,Ewig et al, Thorax 2002; 57:366,Effect of Early Administration of Antibiotics on Outcomes,Houck PM et al. Arch Intern Med 2004; 164:637-44,Early Administration of Abx significantly decrease mortality and LOS,Start empirical antibiotic therapy as soon as possible,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的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,急性发热 WBC不高/淋巴增高（无感染灶）病毒！ WBC增高/中性粒增高/核左移 可能细菌！ 部位/病原体？ 原发性菌血症？慢性发热 IE、布病、慢性感染灶？结核病？ 非感染性发热 药物热、风湿病、恶性肿瘤,正确诊断是正确治疗的前提,发热的诊断与鉴别诊断,Cryptogenic Organizing Pneumonia,Infectious Diseases Expert Resources,Infectious Diseases Specialists,Optimal Patient Care,Infection Control Professionals,Healthcare Epidemiologists,ClinicalPharmacists,Clinical Pharmacologists,Surgical InfectionExperts,ClinicalMicrobiologists,选择哪种抗菌药物(which antibiotic?) 感染部位的常见病原学(possible pathogens on site of infection) 选择能够覆盖病原体的抗感染药物(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) 肾功能不全/肝功能不全/肝肾功能联合不全(renal/heptic dysfunction/combined)其它因素(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物选择-considerations in choosing antibiotic for empiric therapy,培养结果前依据基本信息选择抗感染药物 choosing Abx before culture result感染部位和可能病原体的关系 association of pathogen with site of infectionGram染色结果-与上述病原体是否符合？ Gram stain-in accordance with suspected pathogen?某些病原体易于造成某些部位的感染 Some pathogen easily cause some site of infection,经验性抗感染治疗药物选择-considerations in choosing antibiotic for empiric therapy,不同感染部位的常见感染性病原体Possible pathogens on site of infection,注意特殊修正因子/特别是先期抗菌药物对细菌学的影响,不同感染部位的常见感染性病原体Possible pathogens on site of infection,关注特殊病原体,肺孢子菌肺炎 -免疫缺陷 -相对特异临床 -积极病原学检查,重症军团菌肺炎发热、少痰多肺叶、多肺段受累肺外表现,抗菌谱(coverage)通读药物说明书和相关资料组织穿透性(tissue penetration) 抗菌药物的特性（antibiotic itself） 脂溶性(lipid solubility)/分子量(MW) 组织特性（血运/炎症）(tissue itself-blood supply and inflammation) 急性感染/慢性感染(acute vs chronic infection) 细胞内病原体(intra vs extracellullar pathogen) 体内特殊生理屏障(physiologic barriers)-血脑屏障、血胰屏障、胎盘屏障等耐药性(resistance, specifically local resistance) 参考代表性资料/依靠当地资料安全性(safety profile) -药物本身/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物选择 能够覆盖可能病原体的抗菌药物（Abx requirements）,抗菌谱(coverage)通读药物说明书和相关资料组织穿透性(tissue penetration) 抗菌药物的特性（antibiotic itself） 脂溶性(lipid solubility)/分子量(MW) 组织特性（血运/炎症）(tissue itself-blood supply and inflammation) 急性感染/慢性感染(acute vs chronic infection) 细胞内病原体(intra vs extracellullar pathogen) 体内特殊生理屏障(physiologic barriers)-血脑屏障、血胰屏障、胎盘屏障等耐药性(resistance, specifically local resistance) 参考代表性资料/依靠当地资料安全性(safety profile) -药物本身/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物选择 能够覆盖可能病原体的抗菌药物（Abx requirements）,评价评价耐药病原体,重症感染耐药菌感染！重症感染革兰阴性杆菌感染！ 军团菌、肺炎链球菌都可致重症感染,是否耐药菌？依据宿主相关因素 -高龄、基础疾病、近期使用抗菌药物、住院 -病人来源：社区、养老院、医院 -耐药病原体流行状况是否重症?-依据临床表现 -氧和、血液动力学、肾功能 肠功能,Risk factors for infection with ESBL producers outside hospital,Colodner et al EJCMID 2004 23, 163.,Prevalence of rectal carriage of Extended-Spectrum -lactamase -producing Escherichia Coli among elderly people in a community setting in Shenyang,横断面研究/整群抽样-276名社区老人、直肠拭子/大肠杆菌ESBL检测、分子分型和PEGF结果:直肠拭子ESBL+大肠杆菌携带率7.0%（19/270）. 19株ESBL+菌株ESBL基因型均为CTX-M 型 12株为CTX-M-14 型（63.2%), 3株 CTX-M-22型, 1株 CTX-M-24型， 2株 CTX-M-57-like型，1株同时产CTX-M-24和CTX-M-57-like型. 序列分析表明CTX-M-57-like基因序列中第865位点发生GA替换,导致 氨基酸序列中第289位点发生DN替换,该基因序列不同于 GenBank数 据库已发表序列，提示新型ESBLs基因型(GenBank 序列号 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 2008;54:15,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,产ESBL细菌感染的危险因素,Prospective study of 455 episodes of K. pneumoniae bacteremia (253 nosocomial) in 12 hospitals30.8% 为医院获得, ICU中43.5%产ESBLsESBLs危险因素 先期使用氧亚氨基-内酰胺类抗菌药物 过去14天内使用2 d (OR= 3.9). 其它危险因素 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 2004; 140:26-32.,VAP耐药菌感染的危险因素,135 次VAP ICU变量 OR PMV7 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,Appropriate Carbapenems Based on Risk for MDR Gram-Negative Pathogens,aExcept 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_2006_W-226364-NL.pdf. Accessed 7 April 2008; Dimopoulos G, Falagas ME. Eur Infect Dis. 2007;4951; Ben-Ami R, et al. Clin Infect Dis. 2006;42(7):925934; Pop-Vicas AE, DAgata EMC. Clin Infect Dis. 2005;40(12):17921798; Shah PM. Clin Microbiol Infect. 2008;14(suppl 1):175180.,S. aureus,Penicillin,1944,Penicillin-resistantS. aureus,金黄色葡萄球菌耐药的发生发展过程,Methicillin,1962,Methicillin-resistantS. aureus (MRSA),Vancomycin-resistantenterococci (VRE),Vancomycin,1990s,1997,VancomycinintermediateS. aureus(VISA),2002,Vancomycin-resistantS. aureus,CDC, MMWR 2002;51(26):565-567,1960,Macrolide resistant S. pneumoniae in Asian Countries: ANSORP 1998-2001,- 555 isolates- macrolide susceptibility- 216 S (38.9%)- 10 I (1.8%)- 329 R (59.3%)Vietnam88.3% RHong Kong 76.5% RTaiwan87.2% RChina75.6% RKorea85.1% R- ermB more common (50%) China, Taiwan, Sri Lanka, Korea.- mefA more common Hong Kong, Singapore, Thailand, Malaysia.- most countries MIC90 12 mg/L.,Song et al, Journal of Antimicrobial Chemotherapy 2004; 53(3):457-463.,红霉素耐药肺炎链球菌表型和基因型,赵铁梅，刘又宁.中华内科杂志.2004;43(5):329-332/AAC,2004;48（10）:4040-4041,耐药表型,基因型,N=148,抗菌谱(coverage)通读药物说明书和相关资料组织穿透性(tissue penetration) 抗菌药物的特性（antibiotic itself） 脂溶性(lipid solubility)/分子量(MW) 组织特性（血运/炎症）(tissue itself-blood supply and inflammation) 急性感染/慢性感染(acute vs chronic infection) 细胞内病原体(intra vs extracellullar pathogen) 体内特殊生理屏障(physiologic barriers)-血脑屏障、血胰屏障、胎盘屏障等耐药性(resistance, specifically local resistance) 参考代表性资料/依靠当地资料安全性(safety profile) -药物本身/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物选择 能够覆盖可能病原体的抗菌药物（Abx requirements）,选择哪种抗菌药物(which antibiotic?) 感染部位的常见病原学(possible pathogens on site of infection) 选择能够覆盖病原体的抗感染药物(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) 肾功能不全/肝功能不全/肝肾功能联合不全(renal/heptic dysfunction/combined)其它因素(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物-considerations in choosing antibiotic for empiric therapy,评估病原体 有的而放矢！评估耐药性 到位不越位！,评估严重性 广谱 VS 窄谱？ 单药 VS 联合？,选择哪种抗菌药物(which antibiotic?) 感染部位的常见病原学(possible pathogens on site of infection) 能够覆盖病原体的抗感染药物(antibiotics requirement) 抗菌谱coverage)/组织穿透性(tissue penetration) /耐药性(resistance pattern) /安全性(safety)/费用(cost)优化药代动力学/药效动力学(optimizing 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) 肾功能不全/肝功能不全/肝肾功能联合不全(renal/heptic dysfunction/combined)其它因素(other considerations) 杀菌和抑菌/单药和联合/静脉和口服/疗程,合理的经验性抗感染治疗药物选择 considerations in choosing antibiotic for empiric therapy,Pharmacology of Antimicrobial Therapy,Dosingregimen,Concentrationsin serum,Concentrationsin tissues and body fluids,Concentrationsat site of infection,Pharmacologic and toxicologic effect,Antimicrobialeffect,AbsorptionDistributionElimination,Pharmacokinetics (PK),Pharmacodynamics (PD),MIC、 MBC,Different pattern of time-killing of 3 Abx VS Pseudomonas,Killing and rate of killing depends on concentration,Rate of killing increases no more as concentration increases, killing depends on exposure time,Time,MIC90,Log Concentration,24h-AUC,T MICCmax, Cmax/MIC24h-AUC/MIC (AUIC),Dose,Dose,Cmax,TMIC,Parameters of interest,PK/PD Predictors of Efficacy,依据PK/PD抗菌药物分类,时间依赖性,与时间有关，但抗菌活性持续时间较长,对致病菌的杀菌作用取决于峰浓度,抗菌作用与同细菌接触时间密切相关,时间依赖且PAE或T1/2较长,氨基糖苷类、氟喹诺酮类、酮内酯类、两性霉素B、 daptomycin、甲硝唑,多数-内酰胺类、林可霉素类恶唑烷酮类、氟胞嘧啶,链阳霉素、四环素、碳青霉烯类、糖肽类、大环内酯类、唑类抗真菌药,主要参数AUC0-24/MIC(AUIC)Cmax/MIC,主要参数 TMIC和AUCMIC,主要参数 TMIC, PAE，T1/2 AUC/MIC,浓度依赖性,Drusano. Clin Infect Dis 2003;36(Suppl. 1):S42S50,Maximizing TMIC提高剂量安全性前体增加给药频率延长输注时间, -内酰胺类优化暴露时间-Lactam: Optimizing Exposure,Optimizing FQs therapy for S. pneumoniae from PK/PD point of view,EfficacyCmax/MIC ratio 8-1024-h AUC/MIC(AUIC) Total AUIC 100 Free AUIC 30-40Resistance preventionCmax MPCHigher AUIC,选择哪种抗菌药物(which antibiotic?) 感染部位的常见病原学(possible pathogens on site of infection) 能够覆盖病原体的抗感染药物(antibiotics requirement) 抗菌谱coverage)/组织穿透性(tissue penetration) /耐药性(resistance pattern) /安全性(safety)/费用(cost)优化药代动力学/药效动力学(optimizing 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) 肾功能不全/肝功能不全/肝肾功能联合不全(renal/heptic dysfunction/combined)其它因素(other considerations) 杀菌和抑菌/单药和联合/静脉和口服/疗程,合理的经验性抗感染治疗药物选择 considerations in choosing antibiotic for empiric therapy,选择哪种抗菌药物(which antibiotic?) 感染部位的常见病原学(possible pathogens on site of infection) 能够覆盖病原体的抗感染药物(antibiotics requirement) 抗菌谱coverage)/组织穿透性(tissue penetration) /耐药性(resistance pattern) /安全性(safety)/费用(cost)优化药代动力学/药效动力学(optimizing 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) 肾功能不全/肝功能不全/肝肾功能联合不全(renal/heptic dysfunction/combined)其它因素(other considerations) 杀菌和抑菌/单药和联合/静脉和口服/疗程,合理的经验性抗感染治疗药物选择 considerations in choosing antibiotic for empiric therapy,选择抗菌药物时应考虑的其它因素 Other considerations in choosing Abx,杀菌 vs 抑菌(Cidal vs static) 严重/复杂感染选杀菌剂 cidal for serious and compicated infections单药 vs 联合(monotherapy vs combination)：静脉 vs 口服(IV vs oral)疗程(duration),联合用药的理由,补充单一用药的抗菌谱不足！协同作用如铜绿假单孢菌菌血症减少耐药？,2007 ATS/IDSA Guidelines: Inpatients,Mandell LA, et al. Clin Infect Dis 2007,CAP Inpatient Therapy,Medical Ward,Intensive Care Unit,RecentAntibiotic,No RecentAntibiotic,Respiratory FQ alone ORAdvanced 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 ORrespiratory FQ*,抗菌药物联合药敏,药物联合能够提高铜绿假单胞菌对药物的敏感率(平均增加3.49.2 ),CID 2005，40(Suppl 2)：S89一S98,Novel Antibiotic Combinations against Infections with Almost Completely Resistant Pseudomonas aeruginosa and Acinetobacter Species,缺乏严格的大规模、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 -在高耐药地区，先联合，药敏 结果明确后考虑停用一种药物,Rahal JJ. CID 2006; 43:S959,联合治疗曾被成功地用于抗结核治疗用于减少耐药性在HAP和医院获得性血流感染中也缺乏结论性证据间接证据证明联合治疗可能有用 丹麦学者对19811995的14年间7938次菌血症分离的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）,选择口服抗菌药物应该考虑,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,8 vs. 15 Days of Antibiotic TherapyVentilator-Associated Pneumonia (contd),Chastre J, et al. JAMA. 2003;290:2588-2598.,前瞻,随机,双盲临床研究 51 法国ICUs至少进行机械通气48 hs药物由治疗医生选择 方案遵从ATS 指南主要观察指标 病死率 微生物学证实的感染复发 VAP发生后28天不用抗菌药物的时间,抗感染药物的临床应用,治疗性应用经验治疗 因无法确定感染的微生物，推断可能的病原体，参考本地区药敏监测结果， 抗生素须覆盖所有可能微生物，常选用联合治疗或单一广谱抗生素,治疗性应用目标治疗 确定病原体，选用窄谱、低毒性的抗生素,预防性应用,抗菌药物预防性应用的基本原则内科和儿科预防用药,抗菌药物临床应用指导原则,有明确应用预防指征者仅限于少数情况原则只能预防一或二种特定病原体只能一段时间内，不能长期使用不用于原发疾病不能治愈或缓解者不用于病毒、昏迷、休克、中毒、心衰、肿瘤不用于病毒性疾病:普通感冒、麻疹、水痘等不用于应用肾上腺皮质激素,预防对象抗菌药物风湿热复发青霉素或红霉素（青霉素过敏者） 流行性脑脊髓膜炎SD、环丙沙星（成人）或头孢曲松 结核病（与排菌者密切接触儿童） 异烟肼 疟疾（进入疫区者） 青篙素、氯喹 新生儿眼炎 四环素、红霉素或硝酸银 实验中不慎直接接触 布鲁菌菌、鼠疫杆菌等 四环素链霉素 菌尿症（孕妇、婴幼儿、老人等）SMZ Co、喹诺酮、阿莫西林,抗菌药物预防性应用的基本原则内科和儿科预防用药,CDC Classification of SSI,From Mangram AJ, et al. Infect Control Hosp Epidemiol. 1999;20:247-278,切口浅部感染术后30天内发生、仅累及皮肤及皮下组织的感染，并至少具备下述情况之一者：1.切口浅层有脓性分泌物2.切口浅层分泌物培养阳性3.具有下列症状体征之一： 疼痛或压痛，肿胀，红热 因而医师将切口开放者（如 培养阴性则不属感染）4.由外科医师或内科主治医 师诊断为切口浅部SSI 注:缝线脓点及戳孔周围感 染不列为手术部位感染,切口深部感染术后