ICU獲得性感染PPT課件

1、Cost of Hospital Stay Associated with ResistanceOrganism/AntibioticUSD (million)MRSE239MRSA122Enterobacter119Ampicillin-resistant E. coli83Imipenem-resistant P. aeruginosa61Vancomycin-resistant Enterococcus37Estimated total costs0.7-1.2 billionOther associated costsSecondary infectionsDays of work l

2、ostPosthospital careOther major costsOverall total estimated costs300 billionValue of A Human Life?Source: OTA Report第1頁/共79頁 an overall risk of 18% of acquiring an infection during ICU stay one of the most common causes of death in ICUs第2頁/共79頁European Prevalence of Infection in Intensive Care Stud

3、y (EPIC) Held on April 29, 1992 an overall of 9567 patients from 1417 ICUs第3頁/共79頁 a total of 45% of patients had an infection ICU-acquired infection21% community-acquired infection14% hospital-acquired infection other than ICU10%第4頁/共79頁InfectionMedicine(%)Surgery(%)ICU(%)LRTI241865UTI433118Soft ti

4、ssue-1112BSI15102Other183013第5頁/共79頁Nosocomial Infection in ICUPredisposing risk factors prolong length of ICU stay antibiotic usage mechanical ventilation urinary catheterization pulmonary artery catheterization central venous access stress ulcer prophylaxis use of steroid nutritional status第6頁/共79

5、頁Nosocomial Infection in ICUDuration of ICU stay - EPIC datalength of ICU stayOR for NI1 - 2 days13 - 4 days35 - 6 days6 21 days33第7頁/共79頁Nosocomial Infection in ICUUse of Antibiotics - EPIC data of 10,038 patients, 62% received antibiotics for either prophylaxis or treatmentA n tib io tic s% o f p

6、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 lyc o s id e2 3 .9m e tro n id a z o le1 7 .1flu o ro q u in o lo n e1 1 .9g lyc o p e p tid e1 1 .6第8頁/共79頁Nosocomial Infection in ICUPrevious exposure to antibiotics modify intestinal flora, leading to colonizat

7、ion with resistant bacteria3rd generation cephalosporinsfluoroquinolonesvancomycin favor the selection of inducible beta-lactamase producing GNB, such as Pseudomonoas aeruginosa, Enterobacter clocae, Serratia spp., and Citrobacter freundii第9頁/共79頁Nosocomial Infection in ICUCommon pathogens community

8、-acquired infection and early ( 4d) hospital-acquired infections Enterobacter spp. Serratia spp. ESBL-producing microorganisms Pseudomonas aeruginosa Acinetobacter spp. MRSA enterococci fungi第11頁/共79頁most common pathogens S. aureus30% P. aeruginosa29% Coagulase-negative staphylococci19% E. coli13% E

9、nterococcus spp.12%第12頁/共79頁Pathogens of nosocomial infection in ICU, PUMCH0%20%40%60%80%100%19951996199719981999Gram-negative bacilliGram-positive rodsFungiOther第13頁/共79頁Gram-negative pathogens in ICU, PUMCH0%20%40%60%80%100%19951996199719981999AcinetobacterCitrobacterEnte robacterE. ColiKlebsiella

10、ProteusP. AeruginosaStenotrophomonas第14頁/共79頁Emerging PathogensGram-negativebacilli58%Gram-positive rod32%Candida10%Gram-negative bacilliGram-positive rodCandidaData from ICU, PUMCH 1999第15頁/共79頁Emerging PathogensS. aureus28%S.Epidermidis34%Strept.9%E. faecalis23%E. faecium6%S. aureusS. EpidermidisS

11、trept.E. faecalisE. faecium第16頁/共79頁Mechanism of Resistance to Beta-lactam AntibioticsDepartment of Critical Care MedicinePeking Union Medical College Hospital第17頁/共79頁Principle of beta-lactam action a rigid bacterial cell wall protects bacteria from mechanical and osmotic insult beta-lactam inhibit

12、s 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第18頁/共79頁Mechanism of Antibiotic ResistanceMech

13、anismExample1. bacterial enzyme production resulting indestruction or structured modification ofantibioticBeta-lactam,macrolide,aminoglycoside2. alteration in bacterial membrane to reduceantibiotic permeabilityQuinolone,aminoglycoside3. alteration in antibiotic target site (e.g.bacterial enzyme of r

14、ibosome)Macrolide, quinolonebeta-lactam,aminoglycoside4. modification of bacterial metabolic path-way resulting in bypass of antibiotic site ofinhibitionTrimethoprime,sulphonamide5. promotion of antibiotic efflux from cell,preventing intracellular accumulation ofantibiotictetracycline第19頁/共79頁Does b

15、eta-lactamase confer resistance? The amount of enzyme products its ability to hydrolyse the antibiotic in question its interplay with the cellular permeability barriers第20頁/共79頁Inducible Beta-lactamase also called class I beta-lactamase or constitutive beta-lactamase or AmpC beta-lactamase most are

16、chromosome-mediated major producers Pseudomonas aeruginosa Enterobacter sp. Citrobacter sp. Serratia sp. Morganella morgannii第21頁/共79頁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 re

17、moved low level insufficient to protect bacteria even against drugs rapidly hydrolysed by the enzymes enzyme hyperproducer = mutants that produce Class I enzymes continuously at a high level第22頁/共79頁Inducible Beta-lactamaseStrong inducerWeak inducerLabile1st generation cephalo-sporins, ampicillin, c

18、efo-xitin2nd and 3rd generationcephalosporins, ureido-penicillins, monobactamsStableImipenemtemocillinInduction 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頁/共79頁Activ

19、ity of Drugs Against Organisms with Elevated Beta-Lactamase Levels Decreased ActivityMonobactamsSecond-, Third-generation cephalosporinsBroad-spectrum penicillins Maintain ActivityImipenem, MeropenemFourth-generation cephalosporinsCiprofloxacin, ofloxacin, etcSMZ/TMPco (except P. Aeruginosa)Aminogly

20、cosides第24頁/共79頁Antibiogram of Enterobacter19951996199719981999PIP18%23%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頁/共79頁Enterobacter Bacteremia: Clinical Features and Emergence of Antibiotic Resistance during TherapyChow JW, et alAnn Int Med 1991; 115: 585

21、-90第26頁/共79頁Multiresistant EnterobacterM 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 weeks before the initial positive blood cultureAssociation of Pre

22、viously Administered Antibiotics withMultiresistant Enterobacter in the Initial Blood Culture第27頁/共79頁Multiresistant EnterobacterAntibiotic TherapyEmergence of Resistanceto the Therapyn/N (%)Third-generation cephalosporin*6/31 (19)Aminoglycoside*1/89 (1)Other beta-lactam*0/50 (0)Emergence of Resista

23、nce 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頁/共79頁Multiresistant EnterobacterVariab leM o r

24、tality*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 erap y1 0

25、 /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頁/共79頁Extended spectrum beta-lactamase Most are plasmid mediated 1 to 4 amino acid changes from broad-spectrum beta-lactamases, therefore greatly extending substra

26、te range Major producers E. Coli (TEM) Klebsiella sp. (SHV) inhibited by beta-lactamase inhibitors第30頁/共79頁Reliable (relatively) agents for ESBL-producing pathogens Carbapenems Amikacin Cephamycins (except MIR-1 type; 30% of strains) Beta-lactamase inhibitorspip/tazo30% R in Chicago 199626% R in ICU

27、, PUMCH 1999第31頁/共79頁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頁/共79頁Antibiogram of Klebsiella19951996199719981999PIP36%12%64%50%8%IMP100%100%100%100%100%CAZ42%19%64%65%42%AMK93%81%100%90%92%CIP64%77%55%65%7

28、5%第33頁/共79頁Prevalence of CAZ-R Klebsiella19901993CAZ-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頁/共79頁Cross-Resistance inCAZ-R

29、Klebsiella19901993GEN/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頁/共79頁Prevalence of ESBLno. of isolatesESBL +veE. coli288 (29%)Klebsiell

30、a pneumoniae4019 (48%)Total6827 (40%)Data from Intensive Care Unit, Peking Union Medical College Hospital, 1999第36頁/共79頁Cross-Resistance inCAZ-R KlebsiellaCAZ-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頁/共79頁Effect of ESBL on

31、 MortalityESBL +(n=32)ESBL (n=184)P valueMortality of Allpatients46%34%Mortality of non-ICU patients40%18%0.06Analysis of mortality in 216 bacteremic patients caused by Klebsiella pneumoniaePatterson et al. 37th ICAAC, 1997, Abstr J-210第38頁/共79頁Effect of ESBL on MortalityMortalityP valueS28%-Sensiti

32、vity profileR75%0.02IMP23%-Antibiotic usedother42%0.07Patterson et al. 37th ICAAC, 1997, Abstr J-210Empiric antibiotic therapy in 32 bacteremic patients caused by ESBL-positive Klebsiella pneumoniae第39頁/共79頁Molecular Epidemiology of CAZ-R E. Coli and K. Pneumoniae Blood IsolatesSchiappa D, et alRush

33、 University and University of Illinois, Chicago ILJournal of infectious Diseases 1996; 174: 529-37第40頁/共79頁Risk Factors for CAZ-RKlebsiella BacteremiaBloodstream 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(5.1

34、8)0.000001XFoley Catheter25 (81)5 (16)0.000001(5.04, 103.5)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頁/共79頁CAZ-R Klebsiella BacteremiaAppropriateTreatment(N=19)Inappropr

35、iateTreatment(N=12)Survived18*7Expired15* Outcome of Patients with CAZ-R Bacteremia Who Received Appropriate vs. Inappropriate Therapy Within 72 Hours of Bacteremic Event第42頁/共79頁Ceftazidime - emergence of resistance Emergence of Antibiotic-Resistant Pseudomonas aeruginosa: Comparison of Risks Assoc

36、iated with Different Antipseudomonal Agents by Carmeli Y, et al. Antimicrobial Agents and Chemotherapy 1999; 43 (6): 1379-82第43頁/共79頁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 a

37、ctivity ceftazidime, ciprofloxacin, imipenem, piperacillin a total of 271 patients (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第44頁/共79頁Ceftazidime - emer

38、gence of resistanceMultivariable 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)0.4Ciprofloxacin12/980.8 (0.3-2.0)0.6Imipenem11/372.8 (1.2-6.6)0.02Piperacillin9/911.7 (0.7-4.1)0.3Table. Multivar

39、iable Cox hazard models for the emergence of resistance to any of the four study drugs第45頁/共79頁Classification of Antibiotic Therapy Prophylactic Use Therapeutic Use Empiric therapy Definitive therapy第46頁/共79頁Empiric Antibiotic TherapyDepartment of Critical Care MedicinePeking Union Medical College H

40、ospital第47頁/共79頁Empiric Antibiotic Therapy When treating seriously ill patients who are at risk of developing septic shock when pathogens are unknown or not confirmed antibiotic selection according to epidemiology of NI in the ward resistance profile of most common pathogens第48頁/共79頁Empiric Antibiot

41、ic Therapy Searching for infection focus collecting samples for culture starting empiric antibiotic therapy as soon as possible referring to definitive antibiotic therapy as soon as possible第49頁/共79頁Antibiotic Therapy and Prognosis Objective: To evaluate the relationship between the adequacy of anti

42、biotic treatment for BSI and clinical outcomes among ICU pts Design: Prospective cohort study Setting: 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第50頁/共79頁Antibiotic Therapy

43、 and Prognosis 147 (29.9%) pts received inadequate antimicrobial 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 (

44、n = 46; 32.6%) SCoN (n = 96; 21.9%) Pseudomonas aeruginosa (n = 22; 10.0%) 第51頁/共79頁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)

45、Independent determinant 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)第52頁/共79頁Antibiotic Therapy and Prognosis Independent predictor of the administration of inadequate antimicrobial tx by multipl

46、e 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 decrements) (OR, 1.37; 95% CI,

47、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)第53頁/共79頁Inappropriate empiric antibiotic therapy Objective: to assess the incidence, risk, and prognosis factors of NP acquired during mechanical ventilation (MV) Settings a 1

48、,000-bed teaching hospital April 1987 through May 1988 Patients 78 (24%) episodes of NP in 322 consecutive mechanically ventilated patients第54頁/共79頁Inappropriate empiric antibiotic therapyOR95% CIP valueThe presence of an ultimately orrapidly fatal underlying disease8.843.5222.20.0018worsening of ac

49、ute 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-surgical ICU compared withpost-cardiac surgery ICU)3.381.705.710.06From: Torres et al.

50、 Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis 1990 Sep;142(3):523-8第55頁/共79頁Difficulty in empiric antibiotic therapy Objective: To assess the frequency of and the reasons for changing empiric antibiotics during the treatment of

51、 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 developed 565 episodes of pneumonia after admission to the

52、 ICU.第56頁/共79頁Difficulty in empiric antibiotic therapy Empiric antibiotics in 490 (86.7%) of the 565 episodes of pneumonia The most frequently used antibiotics amikacin120 cases tobramycin110 ceftazidime 96 cefotaxime 96 Monotherapy in 135 (27.6%) of the 490 episodes Combination of 2 antibiotics in

53、306 episodes (62.4%) Combination of 3 antibiotics in 49 episodes (10%)第57頁/共79頁Difficulty in empiric antibiotic therapy The empiric tx modified in 214 (43.7%) cases isolation of a microorganism not covered by treatment133 (62.1%) cases lack of clinical response77 (36%) development of resistance14 (6

54、.6%) Individual factors associated with modification of empiric treatment identified in the multivariate analysis microorganism not covered(RR 22.02; 95%CI 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 1.2

55、2; 95% CI 1.08 to 1.39; p = 0.0018)第58頁/共79頁Difficulty in empiric antibiotic therapyCompared with appropriate empiric therapy, inappropriate therapy was associated withhigher mortality (p=0.0385)more complications (p0.001)higher incidence of shock (p 38 C or 10,000 or 3,000) purulent bronchial secre

56、tions Interventions: Bronchoscopy with BAL within 24 h of clinical dx of VAP or progression of an infiltrate due to prior VAP or NP All patients received antibiotics, 107 prior to bronchoscopy and 25 immediately after bronchoscopy.第61頁/共79頁Difficulty in empiric antibiotic therapyAntibiotic therapyPr

57、ior 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, Matera J, Jolly EC. Impact of BAL data on the therapy and outcome of ventilator-associa

58、ted pneumonia. Chest 1997 Mar;111(3):676-85 第62頁/共79頁Difficulty in empiric antibiotic therapyMortality 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)inappropriate abx(n=51)unnecessary abx(n=28)MortalityFrom:

59、 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頁/共79頁Hospital Infection ControlDepartment of Critical Care MedicinePeking Union Medical College Hospital第64頁/共79頁S

60、cheduled Changes of Empiric Antibiotic Therapy Objective: To determine the impact of a scheduled change of abx classes, used for the empiric tx of suspected gram-negative bacterial infections, on the incidence of VAP and nosocomial bacteremia Patients: 680 patients undergoing cardiac surgery were ev