ICU获得性感染学习教案

1、会计学1ICU获得性感染获得性感染Organism/AntibioticUSD (million)MRSE239MRSA122Enterobacter119Ampicillin-resistant E. coli83Imipenem-resistant P. aeruginosa61Vancomycin-resistant Enterococcus37Estimated total costs0.7-1.2 billionOther associated costsSecondary infectionsDays of work lostPosthospital careOther major

2、 costsOverall total estimated costs300 billionValue of A Human Life?Source: OTA Report第1页/共79页第2页/共79页第3页/共79页10%第4页/共79页InfectionMedicine(%)Surgery(%)ICU(%)LRTI241865UTI433118Soft tissue-1112BSI15102Other183013第5页/共79页 pulmonary artery catheterizationcentral venous accessstress ulcer prophylaxis us

3、e of steroid nutritional status第6页/共79页Duration of ICU stay - EPIC datalength of ICU stayOR for NI1 - 2 days13 - 4 days35 - 6 days6 21 days33第7页/共79页A n tib io tic s% o f p ts w ith a b xc e p h a lo s p o rin s4 4b ro a d -s p e c tru m P C N2 4 .3a m in o g ly c o s id e2 3 .9m e tro n id a z o le

4、1 7 .1flu o ro q u in o lo n e1 1 .9g ly c o p e p tid e1 1 .6第8页/共79页第9页/共79页第10页/共79页第11页/共79页n13%nEnterococcus spp.12%第12页/共79页Pathogens of nosocomial infection in ICU, PUMCH0%20%40%60%80%100%19951996199719981999Gram-negative bacilliGram-positive rodsFungiOther第13页/共79页Gram-negative pathogens in

5、ICU, PUMCH0%20%40%60%80%100%19951996199719981999AcinetobacterCitrobacterEnte robacterE. ColiKlebsiellaProteusP. AeruginosaStenotrophomonas第14页/共79页Gram-negativebacilli58%Gram-positive rod32%Candida10%Gram-negative bacilliGram-positive rodCandidaData from ICU, PUMCH 1999第15页/共79页S. aureus28%S.Epiderm

6、idis34%Strept.9%E. faecalis23%E. faecium6%S. aureusS. EpidermidisStrept.E. faecalisE. faecium第16页/共79页第17页/共79页第18页/共79页MechanismExample1. bacterial enzyme production resulting indestruction or structured modification ofantibioticBeta-lactam,macrolide,aminoglycoside2. alteration in bacterial membran

7、e to reduceantibiotic permeabilityQuinolone,aminoglycoside3. alteration in antibiotic target site (e.g.bacterial enzyme of ribosome)Macrolide, quinolonebeta-lactam,aminoglycoside4. modification of bacterial metabolic path-way resulting in bypass of antibiotic site ofinhibitionTrimethoprime,sulphonam

8、ide5. promotion of antibiotic efflux from cell,preventing intracellular accumulation ofantibiotictetracycline第19页/共79页第20页/共79页第21页/共79页第22页/共79页Strong inducerWeak inducerLabile1st generation cephalo-sporins, ampicillin, cefo-xitin2nd and 3rd generationcephalosporins, ureido-penicillins, monobactams

9、StableImipenemtemocillinInduction 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 replaced by a weak inducer.第23页/共79页Activity of Drugs Against Organisms with Elevated Beta-Lactamase LevelsDecreased Ac

10、tivity Monobactams Second-, Third-generation cephalosporins Broad-spectrum penicillinsMaintain Activity Imipenem, Meropenem Fourth-generation cephalosporins Ciprofloxacin, ofloxacin, etc SMZ/TMPco (except P. Aeruginosa) Aminoglycosides第24页/共79页Antibiogram of Enterobacter19951996199719981999PIP18%23%

11、44%33%5%IMP100%92%100%83%95%CAZ36%31%33%50%21%AMK100%91%88%67%74%CIP82%85%78%45%74%第25页/共79页第26页/共79页M ultiresistantEnterobacter IsolatesAntibiotic*n/N (% )P valueAny antibioticYes36/103 (35)No1/26 (4)0.002Third-generation cephalosporinYes22/32 (69)No14/71 (20)0.001*Antibiotics received in the 2 wee

12、ks before the initial positive blood cultureAssociation of Previously Administered Antibiotics withMultiresistant Enterobacter in the Initial Blood Culture第27页/共79页Antibiotic TherapyEmergence of Resistanceto the Therapyn/N (%)Third-generation cephalosporin*6/31 (19)Aminoglycoside*1/89 (1)Other beta-

13、lactam*0/50 (0)Emergence of Resistance to Cephalosporin, Aminoglycoside, and Other Beta-Lactam Therapy* Cefotaxime, ceftazidime, ceftriaxone, ceftizoxime* Gentamicin, tobramicin, amikacin, netilmicin* Imipenem, piperacillin, ticarcillin, aztreonam, mezlocillin, ticarcillin-clavulanate第28页/共79页Variab

14、 leM o rtality*P v alu en /N (% )R esistan ceM u ltiresistan t E n tero b acter1 2 /3 7 (3 2 )N o n m u ltiresistan t E n tero b acter1 4 /9 2 (1 5 )0 .0 3S u rg eryR ecen t su rg ery1 7 /5 6 (3 0 )N o recen t su rg ery9 /7 3 (1 2 )0 .0 1T h erap yM o n o th erap y9 /5 4 (1 7 )C o m b in atio n th e

15、rap y1 0 /6 4 (1 6 )In ap p ro p riate th erap y7 /11 (6 3 )0 .0 0 1Factors Associated with Mortality in Patients with Enterobacter Bacteremia第29页/共79页第30页/共79页Reliable (relatively) agents for ESBL-producing pathogensCarbapenemsAmikacin Cephamycins (except MIR-1 type; 30% of strains) Beta-lactamase

16、inhibitorspip/tazo30% R in Chicago 199626% R in ICU, PUMCH 1999第31页/共79页Antibiogram of E. coli19951996199719981999PIP0%0%55%35%13%IMP94%100%100%95%94%CAZ33%45%91%79%65%AMK83%100%100%89%76%CIP0%8%73%39%29%第32页/共79页Antibiogram of Klebsiella19951996199719981999PIP36%12%64%50%8%IMP100%100%100%100%100%CA

17、Z42%19%64%65%42%AMK93%81%100%90%92%CIP64%77%55%65%75%第33页/共79页19901993CAZ-R Klebsiella5.2%15.2%Highest in teaching hospitals 500 beds21.8%From Itokazu G, et al. Nationwide Study of Multiresistance Among Gram-Negative Bacilli from ICU patientsClinical Infectious Diseases 1996; 23: 779-85第34页/共79页1990

18、1993GEN/TOBRA62%73%CIP39.8%51.8%Among CAZ-S Klebsiella both 5%From Itokazu G, et al. Nationwide Study of Multiresistance Among Gram-Negative Bacilli from ICU patientsClinical Infectious Diseases 1996; 23: 779-85第35页/共79页no. of isolatesESBL +veE. coli288 (29%)Klebsiella pneumoniae4019 (48%)Total6827

19、(40%)Data from Intensive Care Unit, Peking Union Medical College Hospital, 1999第36页/共79页CAZ-S(n=51)CAZ-R(n=75)GEN27%81%CIP22%36%Data from Intensive Care Unit, Peking Union Medical College Hospital, 1995-1999第37页/共79页ESBL +(n=32)ESBL (n=184)P valueMortality of Allpatients46%34%Mortality of non-ICU pa

20、tients40%18%0.06Analysis of mortality in 216 bacteremic patients caused by Klebsiella pneumoniaePatterson et al. 37th ICAAC, 1997, Abstr J-210第38页/共79页MortalityP valueS28%-Sensitivity profileR75%0.02IMP23%-Antibiotic usedother42%0.07Patterson et al. 37th ICAAC, 1997, Abstr J-210Empiric antibiotic th

21、erapy in 32 bacteremic patients caused by ESBL-positive Klebsiella pneumoniae第39页/共79页第40页/共79页Bloodstream IsolatesCharacteristicsCAZ-R(n=31)CAZ-S(n=31)P value95% CINursing Home Resident18 (52)3 (10)0.0009(2.24, 59.38)APACHE II21.8 (8.7)13.1(5.18)0.000001XFoley Catheter25 (81)5 (16)0.000001(5.04, 10

22、3.5)G or J Tube14 (45)1 (3)0.0004(3.1, 1076.4)Central Venous Catheter27 (67)11 (36)0.0001(3.01, 58.22)Prior Antibiotics20 (54)8 (26)0.001(2.00, 27.22)CAZ or ATM11 (38)00.009X第41页/共79页AppropriateTreatment(N=19)InappropriateTreatment(N=12)Survived18*7Expired15* Outcome of Patients with CAZ-R Bacteremi

23、a Who Received Appropriate vs. Inappropriate Therapy Within 72 Hours of Bacteremic Event第42页/共79页第43页/共79页第44页/共79页Multivariable modelAntibioticEvents(no./total Rx)HR (95% CI)P valueCulturing scoreNI2.5 (1.1-6.0)0.04Aminoglycosides13/770.8 (0.4-2.0)0.8Ceftazidime10/1250.7 (0.3-1.7)0.4Ciprofloxacin12

24、/980.8 (0.3-2.0)0.6Imipenem11/372.8 (1.2-6.6)0.02Piperacillin9/911.7 (0.7-4.1)0.3Table. Multivariable Cox hazard models for the emergence of resistance to any of the four study drugs第45页/共79页第46页/共79页第47页/共79页第48页/共79页第49页/共79页第50页/共79页第51页/共79页第52页/共79页第53页/共79页第54页/共79页OR95% CIP valueThe presence

25、of an ultimately orrapidly fatal underlying disease8.843.5222.20.0018worsening of acute respiratoryfailure caused by pneumonia11.944.75300.0096the presence of septic shock2.831.415.780.016an inappropriate antibiotic tx5.812.70-12.480.02the type of ICU hospitalization(noncardiac surgerical and non-su

26、rgical ICU compared withpost-cardiac surgery ICU)3.381.705.710.06From: 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第55页/共79页第56页/共79页第57页/共79页第58页/共79页Mortality of Patients with Pneumonia Cat

27、egorizedAccording to Empiric Antibiotic Therapy16.20%24.70%0%5%10%15%20%25%30%appropriate abx (n=284)inappropriate abx(n=146)MortalityFrom: Alvarez-Lerma F. Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit. ICU-Acquired Pneumonia Study Group

28、. Intensive Care Med 1996 May;22(5):387-94第59页/共79页第60页/共79页第61页/共79页Antibiotic therapyPrior tobronchoscopyAfterbronchoscopyAfter BAL dataavailableNone60% (9/15)Adequate38% (6/16)71% (30/42)57% (21/37)Inadequate91% (31/34)70% (16/23)40% (2/5)From: Luna CM, Vujacich P, Niederman MS, Vay C, Gherardi C

29、, Matera J, Jolly EC. Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest 1997 Mar;111(3):676-85 第62页/共79页Mortality of Patients with Pneumonia Categorized Accordingto Empiric Antibiotic Therapy33.30%60.80%14.30%0%10%20%30%40%50%60%70%appropriate abx(n=51)inappropr

30、iate abx(n=51)unnecessary abx(n=28)MortalityFrom: Kollef MH, Ward S The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia. Chest 1998 Feb;113(2):412-20第63页/共79页第64页/共79页第65页/共79页Before-period(n=327)After-period(n=353)P v

31、alueVAP incidence11.6%6.7%0.028incidence of VAP attributed toabx-resistant G-bacteria4.0%0.9%0.013incidence of bacteremiaattributed to abx-resistant G-bacteria1.7%0.3%0.125From: Kollef MH, Vlasnik J, Sharpless L, Pasque C, Murphy D, Fraser V Scheduled change of antibiotic classes: a strategy to decr

32、ease the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med 1997 Oct;156(4 Pt 1):1040-8 第66页/共79页第67页/共79页Time period 1Time period 2Time period 3P valueOverall administration ofinadequate antimicrobial therapy for nosocomial infections6.1%4.7%4.5%0.15Overall administration of in

33、adequate antibiotic treatment fornosocomial gram-negative bacterial infection4.4%2.1%1.6%0.001Hospital mortality rate of patients with APACHE II 1521%28%0.001From Kollef MH. The clinical impact of scheduled antibiotic class changes for the empiric treatment of nosocomial gram-negative bacterial infe

34、ctions in the intensive care unit (ICU) setting. Abstracts of 39th ICAAC 1999: 594第68页/共79页第69页/共79页第70页/共79页IndicationEmpiric antibioticsIntra-abdominal infectionCommunity-acquiredAmpicillin/sulbactamAmpicillin/metronidazole/gentamicinNosocomialImipenem/cilastin,ticarcillin/clavulanateLRTICommunity

35、-acquiredAmpicillin/sulbactam, cefuroxime+/- macrolideNosocomialImipenem, piperacillin, ticarcillin/clavulanate+/- tobramicin第71页/共79页Clinical Practice Guideline - empiric antibioticsIndicationEmpiric antibioticsUTI (nosocomial)Community-acquiredAmpicillin+gentamicinNosocomialPiperacillin+gentamicinSoft tissue infection(cellulitis/wound)Nafcillin, cefazolin, or vancomycinDiabetic foot infectAmpicillin/sulbactam第72页/共79页Clinica