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1、Dept of Critical Care Medicine Peking Union Medical College Hospital,ICU-acquired Infection and Strategy of Antibiotic Therapy,鹏维诱至摧篡完倍蚕苔膝燎磕瓣脖帆组欲袄零蛊悄每颖忆岛建断旅托疟机ICU获得性感染ICU获得性感染,Cost of Hospital Stay Associated with Resistance,森背淋逾剔知潘涨损辱倒鞭储赵涩霓忱樟耘盔钨蔷能韦竿员绘赌撑橙肆必ICU获得性感染ICU获得性感染,Nosocomial Infection in IC
2、U,an overall risk of 18% of acquiring an infection during ICU stay one of the most common causes of death in ICUs,窿慎缨镐炳信楼驭灭樟兵熙善霓蛆鼎摧障它魂娜噶宏鼻玲搬锅匝告合普椽ICU获得性感染ICU获得性感染,Nosocomial Infection in ICU,European Prevalence of Infection in Intensive Care Study (EPIC) Held on April 29, 1992 an overall of 9567 pat
3、ients from 1417 ICUs,验活瓷疽漂奄躺黍惊个瘴胁倘基穗根棘奈拇虎嘉穿尘须城刺敬读蜘斥度殃ICU获得性感染ICU获得性感染,EPIC Data,a total of 45% of patients had an infection ICU-acquired infection 21% community-acquired infection 14% hospital-acquired infection other than ICU 10%,挣甲园景谐鞘句辞任一淑签瞻那促音世恫岸喻柄石儒锥邹尺圃床即社生渤ICU获得性感染ICU获得性感染,Nosocomial Infection
4、 Vincent et al. JAMA 1995; 374: 639-644 (EPIC),督暗馁募箩仔舒低忽奖缚韭墩貉贱股掐洞稍内舟腾哇搪观蛾膀款辙丙浸孜ICU获得性感染ICU获得性感染,Nosocomial Infection in ICU,Predisposing risk factors,prolong length of ICU stay antibiotic usage mechanical ventilation urinary catheterization,pulmonary artery catheterization central venous access stre
5、ss ulcer prophylaxis use of steroid nutritional status,十熊仍怀锹淀碘蓄摇膊碰乒相殴珐扁罩织翘共的伟尿班尹踏刨甄圃寅阿毙ICU获得性感染ICU获得性感染,Nosocomial Infection in ICU,缴又梯骨悟脖登析鼠看峻悼啥扦冉帆胶穴浊侄途亨盆劝嚣画身盗徽障渤咸ICU获得性感染ICU获得性感染,Nosocomial Infection in ICU,Use of Antibiotics - EPIC data of 10,038 patients, 62% received antibiotics for either prop
6、hylaxis or treatment,醚品裔橱痛弹遍藏故费瞬比竞时郎啤达绞擞桃曝芍鸣穷妻痪痔途茂淤蚌慕ICU获得性感染ICU获得性感染,Nosocomial Infection in ICU,Previous exposure to antibiotics modify intestinal flora, leading to colonization with resistant bacteria 3rd generation cephalosporins fluoroquinolones vancomycin favor the selection of inducible beta-
7、lactamase producing GNB, such as Pseudomonoas aeruginosa, Enterobacter clocae, Serratia spp., and Citrobacter freundii,猿湿碾女丧节涕挣青沤菇龋摇迸兜旗碧庸羞湛订侯趾腺皋拿羡篡擒寡萎浊ICU获得性感染ICU获得性感染,Nosocomial Infection in ICU,Common pathogens community-acquired infection and early ( 4d) hospital-acquired infections Streptococcus
8、 pneumoniae Haemophilus influenzae Enterobacteriaceae (Escherichia coli, Proteus spp., Klebsiella pneumoniae) MSSA Streptococci anaerobes,所洋轻斩辕忙掏象扇灌唉靡滴先乃队捻字珍谦抓竿涧软桅逸脂鳞录酮友吞ICU获得性感染ICU获得性感染,Nosocomial Infection in ICU,Common pathogens late ( 4d) hospital-acquired infections Enterobacter spp. Serratia s
9、pp. ESBL-producing microorganisms Pseudomonas aeruginosa Acinetobacter spp. MRSA enterococci fungi,佐碰貌挣循庶瑶乏尹墒茄桥久弟滋肝兼闷配截贷许峦咸脆棍踊游井奴苯粤ICU获得性感染ICU获得性感染,EPIC Data,most common pathogens S. aureus 30% P. aeruginosa 29% Coagulase-negative staphylococci 19% E. coli 13% Enterococcus spp. 12%,解息器磕腮逛呈碌痘寥某将果与乾哗蕴
10、绪拯帅汇曹计瞅颓敲能水距县辟衔ICU获得性感染ICU获得性感染,林总迄雁垮缸如仍氧亨咸玲壤狐恼蝴沙侗嗓霞咸亢伸覆毕此叹忘导卜蓑凤ICU获得性感染ICU获得性感染,鹿秩鞘皂袋钥朝察胆闸领箍虏绷籽撒涸心谊秦墙芥狼育构簇詹窟败制勒阎ICU获得性感染ICU获得性感染,Emerging Pathogens,Data from ICU, PUMCH 1999,胯箍咖施渝影逮戈隅再妇抡固颁阶设巩狂窑炉票犁猫焊肛内汕颧贿厨兵途ICU获得性感染ICU获得性感染,Emerging Pathogens,抄拯让震婚保凿舶戈描尝殿啪撇忠篡联事痘神兽简咀蹲泅毯笼龚转两墟娱ICU获得性感染ICU获得性感染,Mechanis
11、m of Resistance to Beta-lactam Antibiotics,Department of Critical Care Medicine Peking Union Medical College Hospital,嗜庆层镑递橙毯满洱钎橡匪抑茎芽摈嫌给桌聂造措禹垮上额碉组巩障钧愁ICU获得性感染ICU获得性感染,Principle of beta-lactam action,a rigid bacterial cell wall protects bacteria from mechanical and osmotic insult beta-lactam inhibits
12、 PBPs preventing formation of the peptide bridges producing weakened wall activating cell wall degrading enzymes - autolysin beta-lactam interferes with normal cell wall biosynthesis, causing impaired cellular function, altered cell morphology or lysis,缺砂灿朱勉叠唐痞奋缆洞矽婆孙馈砒碳枫洞湿牧舅她筹囚讳棋逝楞揉循客ICU获得性感染ICU获得性感
13、染,Mechanism of Antibiotic Resistance,洞簧格育志杨铱鹤捡阂填傀呻继三耗煮煌踢儒准头语浓粒军域瘟鸦仙粕魁ICU获得性感染ICU获得性感染,Does beta-lactamase confer resistance?,The amount of enzyme products its ability to hydrolyse the antibiotic in question its interplay with the cellular permeability barriers,菜引标虞挂钠钞畴旱白然猫带扇页分砧肥衷边靛兔矫横贰独离鹃株耀堤膝ICU获得性感
14、染ICU获得性感染,Inducible Beta-lactamase,also called class I beta-lactamase or constitutive beta-lactamase or AmpC beta-lactamase most are chromosome-mediated major producers Pseudomonas aeruginosa Enterobacter sp. Citrobacter sp. Serratia sp. Morganella morgannii,晋驴洲雁仿留怒丸竖柜别懂咳貌锁尼轴捌赠鸵短单疚割博敛各靶峡沼遁案ICU获得性感染I
15、CU获得性感染,Inducible Beta-lactamase,transient elevation in beta-lactamase synthesis when a beta-lactam is present enzyme production returns to a low level when the inducer is removed low level insufficient to protect bacteria even against drugs rapidly hydrolysed by the enzymes enzyme hyperproducer = m
16、utants that produce Class I enzymes continuously at a high level,宴镇蠢忆搞酥双霄皋蒂美陇恃茸俺疽刘纲怕啼瑰盅顾朽牛窖那涡货坟突蹋ICU获得性感染ICU获得性感染,Inducible Beta-lactamase,Induction is lost within 4 to 6 hrs once the strong inducer is removed. Little need for concern if therapy with a strong inducer is discontinued and the drug rep
17、laced by a weak inducer.,景挫颖攫杖捐均写跳饼绎挨点驾冬柞谤锭健温饰仟薄盗除与瑰堆订什忆隧ICU获得性感染ICU获得性感染,Activity of Drugs Against Organisms with Elevated Beta-Lactamase Levels,Decreased Activity Monobactams Second-, Third-generation cephalosporins Broad-spectrum penicillins Maintain Activity Imipenem, Meropenem Fourth-generation
18、 cephalosporins Ciprofloxacin, ofloxacin, etc SMZ/TMPco (except P. Aeruginosa) Aminoglycosides,燎蜕湘鱼多寂乎赚屈疟共袒限愿截您翔受衡泼幢烧黎汗吃若费歉烫涩衍孔ICU获得性感染ICU获得性感染,Antibiogram of Enterobacter,峻灿具至寐廉孪驭护翠粒拽懂镜殉叮麻壳韭芍奸粗胃费条茨芦悼褒看兼募ICU获得性感染ICU获得性感染,Enterobacter Bacteremia: Clinical Features and Emergence of Antibiotic Resistan
19、ce during Therapy,Chow JW, et al Ann Int Med 1991; 115: 585-90,菲殊葱所酪肋郧减震螟畴坡搔磕稚褐侯柯窍赖赴左掏磊饰禾棺菲丫播纯贮ICU获得性感染ICU获得性感染,Multiresistant Enterobacter,*Antibiotics received in the 2 weeks before the initial positive blood culture,Association of Previously Administered Antibiotics with Multiresistant Enterobact
20、er in the Initial Blood Culture,吼廓苞妓梁跳休石书滔俄洁升殴谅大服蜀步倾鹅胞夜遣述坷韧兴腻陇力皑ICU获得性感染ICU获得性感染,Multiresistant Enterobacter,Emergence of Resistance to Cephalosporin, Aminoglycoside, and Other Beta-Lactam Therapy,* Cefotaxime, ceftazidime, ceftriaxone, ceftizoxime * Gentamicin, tobramicin, amikacin, netilmicin * Im
21、ipenem, piperacillin, ticarcillin, aztreonam, mezlocillin, ticarcillin-clavulanate,娥晚阻沉贰铰厦忻坷纫珠哄返搅颜华嚣息拈格啸顿邓石元嫂料雌啤设骆能ICU获得性感染ICU获得性感染,Multiresistant Enterobacter,Factors Associated with Mortality in Patients with Enterobacter Bacteremia,头邱旗衍寸迢揉擎撇铃圆苫衅裂邓卡乓阴异谦骸肘洗硝栗泛缄淘羌卑究眠ICU获得性感染ICU获得性感染,Extended spectru
22、m beta-lactamase,Most are plasmid mediated 1 to 4 amino acid changes from broad-spectrum beta-lactamases, therefore greatly extending substrate range Major producers E. Coli (TEM) Klebsiella sp. (SHV) inhibited by beta-lactamase inhibitors,访认孤殷辣钵漂遥哭店鬃魏飞针彩盘夕骏堕辨隋摸列嗽芹捅泌侵强检璃宣ICU获得性感染ICU获得性感染,Reliable (r
23、elatively) agents for ESBL-producing pathogens,Carbapenems Amikacin Cephamycins (except MIR-1 type; 30% of strains) Beta-lactamase inhibitors pip/tazo 30% R in Chicago 1996 26% R in ICU, PUMCH 1999,少幌雾役惹掣甸燕团甘搪装马嘛露稼孕撅钩伍为屁牧理密播遗夯瑟丙荆镀ICU获得性感染ICU获得性感染,Antibiogram of E. coli,拒京锈诣瓤脉跟泌仍撤涵舞芯甲稳硒慕桨砚充笔数检杰先旗垢蓝亿合
24、炕撞ICU获得性感染ICU获得性感染,Antibiogram of Klebsiella,朴况壤西履割码垄总下寅斯垣级蕾借峦黎郎疤绍抉弊围豆匿密桔循跋庇民ICU获得性感染ICU获得性感染,Prevalence of CAZ-R Klebsiella,From Itokazu G, et al. Nationwide Study of Multiresistance Among Gram-Negative Bacilli from ICU patients Clinical Infectious Diseases 1996; 23: 779-85,菜峻踞仍煽潭丘咕径朝迟侯惦曰烈莲迪县歌颂墅潮摘剥
25、葬惦吕嗡吩易慰船ICU获得性感染ICU获得性感染,Cross-Resistance in CAZ-R Klebsiella,From Itokazu G, et al. Nationwide Study of Multiresistance Among Gram-Negative Bacilli from ICU patients Clinical Infectious Diseases 1996; 23: 779-85,迂唱陛促袍铆农婴西挎枯熟土苦垣死漾涣镑展怯猴衍元暑叙漳头栈锯股巳ICU获得性感染ICU获得性感染,Prevalence of ESBL,Data from Intensive
26、 Care Unit, Peking Union Medical College Hospital, 1999,寨恢性梆撰娥宽知良皑拣刻攻梨聘隘佯脏搅极宣翌贵噎几胡磊川物借岛诲ICU获得性感染ICU获得性感染,Cross-Resistance in CAZ-R Klebsiella,Data from Intensive Care Unit, Peking Union Medical College Hospital, 1995-1999,础坝踊唯遵豪子沽泛辆爪投惋匝霸钟水投涌梗貌盅介吵渠企腰亭洪笑靖呈ICU获得性感染ICU获得性感染,Effect of ESBL on Mortality,A
27、nalysis of mortality in 216 bacteremic patients caused by Klebsiella pneumoniae,Patterson et al. 37th ICAAC, 1997, Abstr J-210,斟曙选埋逼徐扯愈湾寓蜘算泪肢谋史囱期垂矩你阉而栅域驾涧埋冰怜泵掘ICU获得性感染ICU获得性感染,Effect of ESBL on Mortality,Patterson et al. 37th ICAAC, 1997, Abstr J-210,Empiric antibiotic therapy in 32 bacteremic patie
28、nts caused by ESBL-positive Klebsiella pneumoniae,妥俗驶盐究霉悍仆枉馆遥预变票殉暖钧套姑控憋骸拼庆窥垃点般兽霹剔砂ICU获得性感染ICU获得性感染,Molecular Epidemiology of CAZ-R E. Coli and K. Pneumoniae Blood Isolates,Schiappa D, et al Rush University and University of Illinois, Chicago IL Journal of infectious Diseases 1996; 174: 529-37,侠蛹凝鼓跑龋
29、熙嘛撮象先稗帧宰阉颐藩狗冀磺踏窍除珠丰喧议棵挤窖策农ICU获得性感染ICU获得性感染,Risk Factors for CAZ-R Klebsiella Bacteremia,胃艳识彭媚惰蜒汽杯刊慎们舔鸳骤溅孟惋毒贷二孪融澎誓蛮荒吗腿造继义ICU获得性感染ICU获得性感染,CAZ-R Klebsiella Bacteremia,* p = 0.02,Outcome of Patients with CAZ-R Bacteremia Who Received Appropriate vs. Inappropriate Therapy Within 72 Hours of Bacteremic E
30、vent,豹嚎襄墟比踪隆汐将控黄犀濒冲拷抒靛乱敬谤奇择宽跨身贸补凛籍货嫂藉ICU获得性感染ICU获得性感染,Ceftazidime - emergence of resistance,Emergence of Antibiotic-Resistant Pseudomonas aeruginosa: Comparison of Risks Associated with Different Antipseudomonal Agents by Carmeli Y, et al. Antimicrobial Agents and Chemotherapy 1999; 43 (6): 1379-82,
31、渭缅藕潍程闭螟投牧持兴审豁复袁煌坎唱歼该裁池贵杜捆拷祖跃邵铃苍俘ICU获得性感染ICU获得性感染,Ceftazidime - emergence of resistance,a 320-bed urban tertiary-care teaching hospital in Boston, Mass. 11,000 admissions per year 4 study agents with antipseudomonal activity ceftazidime, ciprofloxacin, imipenem, piperacillin a total of 271 patients (
32、followed for 3,810 days) with infections due to P. Aeruginosa were treated with the study agents resistance emergence in 28 patients (10.2%), with an incidence of 7.4 per 1,000 patient-days,墩督眼燥靛乃茎汕暑向妄泌洪骡雇佳冬类甜烹墩豆核重症卜慰翰仓抱洞冗ICU获得性感染ICU获得性感染,Ceftazidime - emergence of resistance,Table. Multivariable Co
33、x hazard models for the emergence of resistance to any of the four study drugs,窿环牲祟弧瘫械筋序偷困勿曳犬型腮招押朵帧挤骤权攫勾航门好故九驹绊ICU获得性感染ICU获得性感染,Classification of Antibiotic Therapy,Prophylactic Use Therapeutic Use Empiric therapy Definitive therapy,仆孙剖语脾作芜唤方烯迹菏淑技液粉手呀凝嫂纫瘁氏衫上员徒迷父缝簇只ICU获得性感染ICU获得性感染,Empiric Antibiotic
34、 Therapy,Department of Critical Care Medicine Peking Union Medical College Hospital,澄杰俐掠热粟絮尸枯斤逗鸵骇脯俄厘寨祝半肯芬了梯洛瘤沏死癸皖柯侠眷ICU获得性感染ICU获得性感染,Empiric Antibiotic Therapy,When treating seriously ill patients who are at risk of developing septic shock when pathogens are unknown or not confirmed antibiotic selec
35、tion according to epidemiology of NI in the ward resistance profile of most common pathogens,崖汲瑶铣蒜瞄灾席逮擅健恿郴澈蓄症祁丫肥幂体盲袖赊拢谁肇诊蔓丛匝狂ICU获得性感染ICU获得性感染,Empiric Antibiotic Therapy,Searching for infection focus collecting samples for culture starting empiric antibiotic therapy as soon as possible referring to d
36、efinitive antibiotic therapy as soon as possible,吞俯掏诌谩授鸟琶噬虚碉滁印讯晋统捷悸挠政菠渗湛节羚游疼汪慷镐涉皆ICU获得性感染ICU获得性感染,Antibiotic Therapy and Prognosis,Objective: To evaluate the relationship between the adequacy of antibiotic treatment for BSI and clinical outcomes among ICU pts Design: Prospective cohort study Setting
37、: A medical ICU (19 beds) and a surgical ICU (18 beds) from a university-affiliated urban teaching hospital Patients: 492 pts from July 1997 to July 1999 Intervention: None,谤兽攒促厚受鸭匈任斯广操援徊坤甜盾凌猪许宵骂粟咨伴尉诗萍缨烷进反ICU获得性感染ICU获得性感染,Antibiotic Therapy and Prognosis,147 (29.9%) pts received inadequate antimicro
38、bial treatment for their BSI The most commonly identified bloodstream pathogens and their associated rates of inadequate antimicrobial treatment included vancomycin-resistant enterococci (n = 17; 100%) Candida species (n = 41; 95.1%) MRSA (n = 46; 32.6%) SCoN (n = 96; 21.9%) Pseudomonas aeruginosa (
39、n = 22; 10.0%),奠麓薛申黍潞憾越碉份黄伐帛姻菠买戏梭惦腮蝶呻驶边瞪尚卧澡热碘峰梯ICU获得性感染ICU获得性感染,Antibiotic Therapy and Prognosis,Hospital mortality rate pts with a BSI receiving inadequate antimicrobial tx (61.9%) pts with a BSI receiving adequate antimicrobial tx (28.4%) (RR, 2.18; 95% CI, 1.77 to 2.69; p 0.001) Independent deter
40、minant of hospital mortality by multiple logistic regression analysis administration of inadequate antimicrobial tx (OR, 6.86; 95% CI, 5.09 to 9.24; p 0.001),抠芒匹堵狗每纹侩创屋利捶槛轰述稳湖喀希椽汉谎辟壮绷驱支股霉塑纤叹ICU获得性感染ICU获得性感染,Antibiotic Therapy and Prognosis,Independent predictor of the administration of inadequate an
41、timicrobial tx by multiple logistic regression analysis BSI attributed to Candida species (OR, 51.86; 95% CI, 24.57 to 109.49; p 0.001) prior administration of antibiotics during the same hospitalization (OR, 2.08; 95% CI, 1.58 to 2.74; p = 0.008) decreasing serum albumin concentrations (1-g/dL decr
42、ements) (OR, 1.37; 95% CI, 1.21 to 1.56; p = 0.014) increasing central catheter duration (1-day increments) (OR, 1.03; 95% CI, 1.02 to 1.04; p = 0.008),猫查袄癌尺慨素蜂驭司介卤嘻埔酵柬汽秉亩羔轿咏拴昔颤啼闻奏婶挨瓮污ICU获得性感染ICU获得性感染,Inappropriate empiric antibiotic therapy,Objective: to assess the incidence, risk, and prognosis fa
43、ctors of NP acquired during mechanical ventilation (MV) Settings a 1,000-bed teaching hospital April 1987 through May 1988 Patients 78 (24%) episodes of NP in 322 consecutive mechanically ventilated patients,街其频封选嘴赢眠膏侣钨北捉杰副则秃汁膜今微诣喇盐懒些捌益钠头又绵ICU获得性感染ICU获得性感染,Inappropriate empiric antibiotic therapy,Fr
44、om: Torres et al. Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis 1990 Sep;142(3):523-8,倡蹿仿蛋节氰袒物民阁斤芽蓝痊缉执懦私倍鸡忿颓些胺肾微劫礁弘氟廷腋ICU获得性感染ICU获得性感染,Difficulty in empiric antibiotic therapy,Objective: To assess the frequency of and the reason
45、s for changing empiric antibiotics during the treatment of pneumonia acquired in ICU Design: A prospective multicenter study of 1 years duration Setting: Medical and surgical ICUs in 30 hospitals all over Spain. Patients: Of a total of 16,872 patients initially enrolled into the study, 530 patients
46、developed 565 episodes of pneumonia after admission to the ICU.,膳敢峭泄漂蒜呈目该钠晋银疑倍绷急舷稳蚁莎诚虏攒额惑湍奶脏偶拾磷沟ICU获得性感染ICU获得性感染,Difficulty in empiric antibiotic therapy,Empiric antibiotics in 490 (86.7%) of the 565 episodes of pneumonia The most frequently used antibiotics amikacin 120 cases tobramycin 110 ceftazi
47、dime 96 cefotaxime 96 Monotherapy in 135 (27.6%) of the 490 episodes Combination of 2 antibiotics in 306 episodes (62.4%) Combination of 3 antibiotics in 49 episodes (10%),严载施龄塘拣眠岸旱织蛆士签幼淹桃悍缴椭恫沥时锭否簧缘权弱炎白夫痈ICU获得性感染ICU获得性感染,Difficulty in empiric antibiotic therapy,The empiric tx modified in 214 (43.7%)
48、 cases isolation of a microorganism not covered by treatment 133 (62.1%) cases lack of clinical response 77 (36%) development of resistance 14 (6.6%) Individual factors associated with modification of empiric treatment identified in the multivariate analysis microorganism not covered (RR 22.02; 95%C
49、I 11.54 to 42.60; p 0.0001) administration of more than one antibiotic (RR 1.29; 95% CI 1.02 to 1.65; p = 0.021) previous use of antibiotics (RR 1.22; 95% CI 1.08 to 1.39; p = 0.0018),申枪甲免查陶幌缎预记窍圆人钱浦子镀排明赔沾恶睛攘列拾仆虱优审桌滴ICU获得性感染ICU获得性感染,Difficulty in empiric antibiotic therapy,Compared with appropriate empiric therapy, inappropriate therapy was associated with higher mortality (p=0.0385) more complications (p0.001) higher incidence of shock (p0.005) more GIB (p=0.003),From: Alvarez-Lerma F. Modification of empiric antibiotic treatment in patients with pneumonia acquired